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Preview: MedWorm: Acute Lymphoblastic Leukemia

MedWorm: Acute Lymphoblastic Leukemia provides a medical RSS filtering service. Over 7000 RSS medical sources are combined and output via different filters. This feed contains the latest news and research in the Acute Lymphoblastic Leukemia category.

Last Build Date: Tue, 29 Mar 2016 16:50:40 +0100


Incidence and risk factors for Central Nervous System thrombosis in paediatric acute lymphoblastic leukaemia during intensive asparaginase treatment: a single‐centre cohort study

Sun, 27 Mar 2016 22:00:00 +0100

Summary Central Nervous System (CNS) thrombosis is a complication of acute lymphoblastic leukaemia (ALL) treatment that is potentially associated with significant morbidity and neurological sequelae. Its presumably multifactorial aetiology is poorly characterized. We conducted a single‐centre, retrospective cohort study on 346 ALL paediatric patients (1–16 years old) treated with asparaginase intensive Dana Farber Cancer Institute (DFCI) protocols from 1998 to 2011. The incidence, risk factors and outcome of CNS thrombosis were evaluated. CNS thrombosis occurred in 3·8% (13/346) of the patients (95% confidence interval 2·0–6·3%). Twelve events were diagnosed during intensification, all of which resolved within 2 weeks without neurological sequelae or significant impact in surviv...

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Targeting the mTOR Pathway in Leukemia

Sun, 27 Mar 2016 22:00:00 +0100

This article is protected by copyright. All rights reserved (Source: Journal of Cellular Biochemistry)

Dietary Intake and Childhood Leukemia: The Diet and Acute Lymphoblastic Leukemia Treatment (DALLT) Cohort Study

Sun, 27 Mar 2016 22:00:00 +0100

We present the demographics and nutrient intake at study entry of a prospective cohort evaluating dietary intake in children diagnosed with ALL. (Source: Nutrition)

Bcl6 modulation of acute lymphoblastic leukemia response to chemotherapy.

Sun, 27 Mar 2016 05:28:02 +0100

This study suggests that marrow microenvironment regulation of BCL6 in ALL is one factor that may be involved in the transition between proliferative and quiescent states of ALL cells. Utilizing ALL cell lines, and primary patient tumor cells we observed that tumor cell BCL6 protein abundance is decreased in the presence of primary human bone marrow stromal cells (BMSC) and osteoblasts (HOB). Chemical inhibition, or shRNA knockdown, of BCL6 in ALL cells resulted in diminished ALL proliferation. As many chemotherapy regimens require tumor cell proliferation for optimal efficacy, we investigated the consequences of constitutive BCL6 expression in leukemic cells during co-culture with BMSC or HOB. Forced chronic expression of BCL6 during co-culture with BMSC or HOB sensitized the tumor to che...

Immunotherapy approaches to treat adult acute lymphoblastic leukemia.

Sat, 26 Mar 2016 18:56:02 +0100

Authors: Maino E, Bonifacio M, Scattolin AM, Bassan R Abstract Recent developments in immunotherapy are improving treatment results of B-precursor acute lymphoblastic leukemia. This advancement is promoted by new monoclonal antibodies such as inotuzumab ozogamicin, ofatumumab and blinatumomab, by rituximab, and by genetically engineered chimeric antigen receptor-modified T-cells. These treatments, variously targeting CD22, CD20 and CD19 antigens, yield unprecedented high rates of hematologic and molecular remissions even when used in monotherapy and in chemo-resistant or post-transplantation relapsed patients. Beside the encouraging results in relapsed/refractory disease, these agents may open a totally new era in the frontline management of this illness, redefining treatment stand...

Vaginal Stenosis After Gonadotropin-Releasing Hormone Agonist Therapy During Treatment for Acute Lymphoblastic Leukemia

Sat, 26 Mar 2016 08:13:16 +0100

Abstract: A 26-year-old patient with a history of chemotherapy for acute lymphoblastic leukemia presented with secondary amenorrhea and cyclic abdominal pain, and she was found to have vaginal stenosis due to adhesion of vaginal wall. The cause of the adhesion was considered to be vaginal inflammation induced by anticancer agents themselves. It was also considered that poor estrogenization of vaginal mucosa as a result of gonadotropin-releasing hormone agonist therapy, conducted for ovarian protection during chemotherapy, might have exacerbated it. Because it is more likely than ever for us to encounter patients who will undertake or had undertaken chemotherapy with gonadotropin-releasing hormone agonist therapy, keen observation and proper intervention would be important. (Source: Journal...

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Significance of CD99 expression in T-lineage acute lymphoblastic leukemia.

Fri, 25 Mar 2016 15:40:03 +0100

CONCLUSION: CD99 could be used to complement current strategy relying on TdT for diagnosis and monitoring of minimal residual disease during the post-therapy follow up of T-ALL patients. Further studies are needed to confirm these findings. PMID: 27002769 [PubMed - as supplied by publisher] (Source: Cancer Biomarkers)

Beclin-1 and hypoxia-inducible factor-1α genes expression: Potential biomarkers in acute leukemia patients.

Fri, 25 Mar 2016 15:40:03 +0100

CONCLUSIONS: Both Beclin-1 and HIF-1α could be considered as important biomarkers determinants of pathogenesis and survival in acute leukemia. PMID: 27002764 [PubMed - as supplied by publisher] (Source: Cancer Biomarkers)

[Report] Activation of proto-oncogenes by disruption of chromosome neighborhoods

Thu, 24 Mar 2016 23:00:00 +0100

Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control of key genes depends on chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur within these structures and whether oncogene activation can occur via disruption of insulated neighborhood boundaries in cancer cells. We mapped insulated neighborhoods in T cell acute lymphoblastic leukemia (T-ALL) and found that tumor cell genomes contain recurrent microdeletions that eliminate the boundary sites of insulated neighborhoods containing prominent T-ALL proto-oncogenes. Perturbation of such boundaries in nonmalignant cells was sufficient to activate proto-oncogenes. Mutations affecti...

PAX5 promotes pre-B cell proliferation by regulating the expression of pre-B cell receptor and its downstream signaling

Wed, 23 Mar 2016 23:00:00 +0100

Publication date: May 2016 Source:Molecular Immunology, Volume 73 Author(s): Kai Xue, Jiazhe Song, Yan Yang, Zhi Li, Chunhua Wu, Jinhua Jin, Wenzhe Li PAX5 is indispensable for the commitment of early lymphoid progenitors to the B cell lineage as well as for the development of B cells. Although previous studies have indicated that the Pax5-conditional-knockout mouse exhibited dedifferentiation of mature B cell and the development of aggressive lymphomas, the changes of Pax5 gene expressions in pre-B cells have not been analyzed. To understand the functional importance of Pax5 gene in the proliferation and survival of pre-B cells, we established a Pax5-knockdown model using 70Z/3 pre-B cell line. Pax5 knockdown 70Z/3 cells (70Z/3-KD cells) showed down-regulations of pre-BCR compoun...

Acute pulmonary edema with new giant V wave immediately after pericardiocentesis

Wed, 23 Mar 2016 23:00:00 +0100

A 42-year-old Japanese man was diagnosed as having acute lymphoblastic leukemia and received multi-agent chemotherapy, including doxorubicin, followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in March 2014. As he failed to achieve complete remission, he was admitted to our hospital to undergo repeat allo-HSCT in March 2015. He had no history of cardiovascular disease or hypertension. Echocardiography showed normal left ventricular (LV) function with no pericardial effusion before repeat allo-HSCT (Fig. (Source: International Journal of Cardiology)

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Acute Lymphoblastic Leukemia Transformation in Polycythemia Vera: A Rare Phenomenon

Wed, 23 Mar 2016 23:00:00 +0100

Abstract Leukemic transformation in patients diagnosed with polycythemia vera (PV) is associated with poor prognosis and median survival not exceeding 3 months. To date only a few cases of post-PV acute lymphoblastic leukemia (ALL) have been reported. A 64-year-old female patient developed ALL 4 years after she had met PV criteria. At PV diagnosis a molecular study was positive for the JAK2V617F mutation. Due to high risk features (history of deep vein thrombosis) she was treated with hydroxyurea (HU) with moderate efficacy. She became anemic and thrombocytopenic with mild leukocytosis while still on HU. Blood and bone marrow smears revealed 40 and 100 % of blast cells, respectively. The immunophenotyping of blasts was consistent with a diagnosis of early precursor B cell ALL. ...

Rapid Capture Next‐Generation Sequencing in Clinical Diagnostics of Kinase Pathway Aberrations in B‐Cell Precursor ALL

Wed, 23 Mar 2016 19:08:02 +0100

Comprehensive next‐generation sequencing (NGS) applications have recently identified various recurrent kinase and cytokine receptor rearrangements in Ph‐like B‐cell precursor (BCP) acute lymphoblastic leukemia (ALL) amenable to tyrosin kinase inhibitor treatment. For rapid diagnostics of kinase pathway aberrations in minimal residual disease (MRD) high‐risk BCP‐ALL, we developed a PCR‐independent NGS custom enrichment capture panel targeting recurrent genomic alterations, which allows for the identification of unknown 5′ fusion partner genes and precise mapping of variable genomic breakpoints. Using a standardized bioinformatics algorithm, we identified kinase and cytokine receptor rearrangements in the majority of ALL patients with high burden of postinduction MRD and enrich...

The complex translocation (9;14;14) involving IGH and CEBPE genes suggests a new subgroup in B-lineage acute lymphoblastic leukemia

Wed, 23 Mar 2016 07:43:49 +0100

We report here the case of a 5-year-old girl with B-ALL, positive for CD19, CD38 and HLA-DR. A direct technique and G-banding were used for chromosomal analysis and fluorescentin situ hybridization (FISH) with BAC probes was used to investigate a possible rearrangement of the IGH andCEBPE genes. The karyotype exhibit the chromosomal aberration 46,XX,del(9)(p21),t(14;14)(q11;q32). FISH with dual-color break-apartIGH-specific and CEPBE-specific bacterial artificial chromosome (BAC) probes showed a complex t(9;14;14) associated with a deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A) and paired box gene 5 (PAX5) at 9p21-13 and duplication of the fusion gene IGH-CEBPE. (Source: Genetics and Molecular Biology)

Leukemic optic nerve infiltration in a patient with acute lymphoblastic leukemia

Wed, 23 Mar 2016 04:26:49 +0100

Conclusion: Isolated optic nerve relapse of leukemic infiltration is of paramount importance to early diagnosis, as vision can be saved if treatment is initiated promptly. (Source: Retinal Cases and Brief Reports)

Outcome of children and adolescents with lymphoblastic lymphoma

Wed, 23 Mar 2016 03:16:17 +0100

Conclusion: our findings confirm the favorable prognosis of children with LBL with an intensive chemotherapy regimen derived from ALL therapy.RESUMO Objetivos: linfoma linfoblástico (LL) é o segundo subtipo mais comum de linfoma não Hodgkin em crianças. O objetivo deste estudo foi caracterizar a evolução clínica de crianças e adolescentes com LL em um centro terciário. Métodos: estudo de coorte retrospectivo de 27 pacientes com idade de até 16 anos com LL admitidos entre janeiro de 1981 e dezembro de 2013. Os pacientes foram tratados de acordo com o protocolo de tratamento para leucemia linfoblástica aguda (LLA). O diagnóstico foi baseado em biópsia do tumor e/ou no exame citológico de derrame pleural. A sobrevida global foi analisada pelo método de Kaplan-Meier. Resultados...

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Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease [Hematologic Malignancy]

Tue, 22 Mar 2016 23:00:00 +0100

Conclusion Allogeneic anti-CD19 CAR T cells can effectively treat B-cell malignancies that progress after alloHSCT. The findings point toward a future when antigen-specific T-cell therapies will play a central role in alloHSCT. (Source: Journal of Clinical Oncology)

Reduction in Cell Viability and in Homeobox Protein Levels Following in Vitro Exposure to δ-tocopherol in Acute Myeloid Leukemia.

Tue, 22 Mar 2016 23:00:00 +0100

In this study, we screened the efficacy of δ-T against six cell lines representing a wide spectrum of hematologic malignancies: Jurkat (acute T-cell leukemia), K-562 (chronic myeloid leukemia), KG-1 [acute myeloid leukemia (AML)], THP-1 (acute monocytic leukemia), TOM-1 (acute lymphoblastic leukemia), and UMCL01-101 (AIDS-associated diffuse large B-cell lymphoma). Interestingly, the AML cell line KG-1 was the only one to be significantly affected at concentrations of δ-T as low as 20 µM. The antileukemic activity of δ-T in AML was verified in a set of primary cells collected from patients newly diagnosed with AML. Apoptotic induction and cell cycle arrest explained the efficacy of δ-T against KG-1 cells. The mechanism of cell growth inhibition of δ-T was through downregulation of cy...

Significance of BAFF/APRIL Expression and Their Receptors in Pediatric Patients With Acute Lymphoblastic Leukemia

Tue, 22 Mar 2016 07:43:43 +0100

In this study, we investigated the mRNA expression and protein levels of B-cell activating factor (BAFF)/a proliferation-inducing ligand (APRIL) and their receptors in acute lymphoblastic leukemia (ALL) cell lines and pediatric patients with ALL using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. The location and level of the BAFF/APRIL proteins in ALL cell lines were also detected by immunofluorescence cytochemistry and flow cytometry. Correlations between plasma protein levels of BAFF/APRIL and primary clinical parameters were analyzed. We found that BAFF/APRIL was highly expressed in pediatric ALL patients and ALL cell lines. The BAFF/APRIL proteins were located on the cell membrane, and the proportion of positive cells and mean fluorescen...

Strategies to Prevent and Manage Thrombotic Complications of Acute Lymphoblastic Leukemia in Children and Young People Vary Between Centers in the United Kingdom

Tue, 22 Mar 2016 07:43:43 +0100

There is a lack of evidence-based guidance for the prevention and management of thrombosis in children and young people treated for acute lymphoblastic leukemia. To determine current UK practice, a survey was sent to 28 centers participating in the Medical Research Council UKALL 2011 trial. Marked variation in practice was noted. In total, 43% of centers defer central venous access device insertion until end of induction for treatment of low-risk disease. Central venous access devices are removed at the end of intensive blocks in 38% and end of treatment in 42%. Duration of anticoagulation for line-associated thrombosis is 6 weeks in 43% and 3 months in 33% and for cerebral sinovenous thrombosis is 3 months in 71% and 6 months in 24%. Platelet transfusion to maintain platelet count >50×10...

Severe Hypercalcemia in a Child With Acute Lymphoblastic Leukemia Relapse: Successful Management With Combination of Calcitonin and Bisphosphonate

Tue, 22 Mar 2016 07:43:43 +0100

In conclusion, because of the postponed effect of bisphosphonate treatment, pamidronate and calcitonin combination is an effective treatment option in the early resolution of malignancy-related hypercalcemia. (Source: Journal of Pediatric Hematology Oncology)

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Early-onset SMART Syndrome in an 11-Year-old Child With Acute Lymphoblastic Leukemia

Tue, 22 Mar 2016 07:43:43 +0100

No abstract available (Source: Journal of Pediatric Hematology Oncology)

Central Venous Catheters and Bloodstream Infection During Induction Therapy in Children With Acute Lymphoblastic Leukemia

Tue, 22 Mar 2016 07:43:43 +0100

The purpose of the study was to assess the risk of first-time bloodstream infection (BSI) according to type of central venous catheter (CVC) during induction therapy in children with acute lymphoblastic leukemia (ALL). Patients eligible for our analysis were all newly diagnosed children with ALL treated at 3 pediatric centers in Denmark between 2008 and 2014. A total of 136 patients were followed from initial CVC placement until first BSI, CVC removal, death, or day 28, whichever occurred first. Thirty-nine BSIs were detected, of which 67% were gram-positive infections, and 59% met the criteria for being CVC associated. The 28-day cumulative incidence of BSI was similar in 77 patients with a nontunneled CVC (28%; 95% confidence interval, 19%-40%) and in 59 patients with a tunneled CVC with...

RUNX1 Amplification Increases the Risk for Thrombosis in Children With B-cell Acute Lymphoblastic Leukemia

Tue, 22 Mar 2016 07:43:43 +0100

Conclusions: RUNX1 amplification may predispose to early thrombotic events in children with B-ALL which could, in part, contribute to their poorer outcomes. Treatment implications, including possible prophylactic anticoagulation of patients with of RUNX1 amplification, justify larger studies to confirm these findings. (Source: Journal of Pediatric Hematology Oncology)

The NEDD8-activating enzyme inhibitor MLN4924 induces G2 arrest and apoptosis in T-cell acute lymphoblastic leukemia.

Mon, 21 Mar 2016 05:47:03 +0100

Authors: Han K, Wang Q, Cao H, Qiu G, Cao J, Li X, Wang J, Shen B, Zhang J Abstract The first-in-class compound MLN4924 is a small molecule inhibitor that selectively inactivates NEDD8-activating enzyme (NAE). The anticancer effects of MLN4924 have been attributed to impaired neddylation of Cullin proteins. Here, we show that treatment of T-cell acute lymphoblastic leukemia (T-ALL) cells with MLN4924 potently suppressed the neddylation of Cullins and the oncogenic growth of T-ALL cells in-vitro. Moreover, MLN4924 induced disease regression in an in vivo xenograft model. MLN4924 also induced cell cycle arrest at G2 phase and apoptosis in T-ALL cells. However, inhibition of the neddylation of Cullins alone could not explain the effects of MLN4924 in T-ALL cells. Gene expression profi...

Unique Familial MLL(KMT2A)‐Rearranged Precursor B‐Cell Infant Acute Lymphoblastic Leukemia in Non‐twin Siblings

Mon, 21 Mar 2016 00:00:00 +0100

ConclusionsWhether because of a deleterious transplacental exposure, novel predisposition syndrome, or exceedingly rare chance occurrence, MLL‐R infant ALL can occur in non‐twin siblings. The discordant occurrence of infant ALL in the monozygous twins was likely because they were dichorionic. (Source: Pediatric Blood and Cancer)

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Strong inflammatory response and Th1-polarization profile in children with acute lymphoblastic leukemia without apparent infection.

Sat, 19 Mar 2016 17:53:03 +0100

Authors: Pérez-Figueroa E, Sánchez-Cuaxospa M, Martínez-Soto KA, Sánchez-Zauco N, Medina-Sansón A, Jiménez-Hernández E, Torres-Nava JR, Félix-Castro JM, Gómez A, Ortega E, Maldonado-Bernal C Abstract Children with acute lymphoblastic leukemia (ALL) often present fever. Febrile states are usually associated with infectious processes that generate an inflammatory response involving various molecules, including cytokines. However, an inflammatory response may also occur in the absence of infection. We hypothesized that the levels of inflammatory cytokines are increased in children with ALL without apparent infection. The serum levels of 13 cytokines in 99 patients with ALL and 48 non-oncological patients without apparent infection were measured using multiplex analyte prof...

Identification of differential PI3K pathway target dependencies in T-cell acute lymphoblastic leukemia through a large cancer cell panel screen.

Sat, 19 Mar 2016 17:51:03 +0100

Authors: Lynch JT, McEwen R, Crafter C, McDermott U, Garnett MJ, Barry ST, Davies BR Abstract Selective phosphoinositide 3-kinase (PI3K)/AKT/mTOR inhibitors are currently under evaluation in clinical studies. To identify tumor types that are sensitive to PI3K pathway inhibitors we screened compounds targeting PI3Kα/δ (AZD8835), PI3Kβ/δ (AZD8186), AKT (AZD5363) and mTORC1/2 (AZD2014) against a cancer cell line panel (971 cell lines). There was an enrichment of hematological malignancies that were sensitive to AKT and mTOR inhibition, with the greatest degree of sensitivity observed in T-cell acute lymphoblastic leukemia (T-ALL). We found that all NOTCH mutant T-ALL cell lines were sensitive to AKT and mTORC1/2 inhibitors, with only partial sensitivity to agents that target the P...

Peripapillary retinal leukemic infiltration associated with papilledema in a T-ALL patient without cranial or optic nerve involvement.

Fri, 18 Mar 2016 12:25:02 +0100

CONCLUSIONS: To our knowledge, there is no other report of peripapillary leukemic infiltration in the absence of retrobulbar optic nerve involvement. We suspect that papilledema might have facilitated peripapillary retinal infiltration due to altered vascular permeability. The reverse could also be possible: leukemic infiltration leading to increase in vascular permeability may also contribute to papilledema. PMID: 26979244 [PubMed - as supplied by publisher] (Source: Tumori)

South Africa: Durban Youngster Wants to Raise Cancer Awareness

Fri, 18 Mar 2016 09:35:16 +0100

[News24Wire] Twenty-year-old Tashnika Rambali was diagnosed with Acute Lymphoblastic Leukaemia when she was just 18, a diagnosis that threw her future into an uncertain spin. (Source: AllAfrica News: Health and Medicine)

Next-generation sequencing for sensitive detection of BCR-ABL1 mutations relevant to tyrosine kinase inhibitor choice in imatinib-resistant patients.

Fri, 18 Mar 2016 05:56:02 +0100

Authors: Soverini S, De Benedittis C, Machova Polakova KM, Linhartova J, Castagnetti F, Gugliotta G, Papayannidis C, Mancini M, Klamova H, Salvucci M, Crugnola M, Iurlo A, Albano F, Russo D, Rosti G, Cavo M, Baccarani M, Martinelli G Abstract In chronic myeloid leukemia (CML) and Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) patients who fail imatinib treatment, BCR-ABL1 mutation profiling by Sanger sequencing (SS) is recommended before changing therapy since detection of specific mutations influences second-generation tyrosine kinase inhibitor (2GTKI) choice. We aimed to assess i) in how many patients who relapse on second-line 2GTKI therapy next generation sequencing (NGS) may track resistant mutations back to the sample collected at the time of imatinib resistan...

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Dibenzo[def,p]chrysene transplacental carcinogenesis in wild‐type, Cyp1b1 knockout, and CYP1B1 humanized mice

Fri, 18 Mar 2016 00:34:13 +0100

The cytochrome P450 (CYP) 1 family is active toward numerous environmental pollutants, including polycyclic aromatic hydrocarbons (PAHs). Utilizing a mouse model, null for Cyp1b1 and expressing human CYP1B1, we tested the hypothesis that hCYP1B1 is important for dibenzo[def,p]chrysene (DBC) transplacental carcinogenesis. Wild‐type mCyp1b1, transgenic hCYP1B1 (mCyp1b1 null background), and mCyp1b1 null mice were assessed. Each litter had an equal number of siblings with Ahrb‐1/d and Ahrd/d alleles. Pregnant mice were dosed (gavage) on gestation day 17 with 6.5 or 12 mg/kg of DBC or corn oil. At 10 months of age, mortality, general health, lymphoid disease and lung tumor incidence, and multiplicity were assessed. hCYP1B1 genotype did not impact lung tumor multiplicity, but tended to en...

Mutations of TP53 in adult acute lymphoblastic leukemia at diagnosis do not affect the achievement of hematologic response but correlate with early relapse and very poor survival.

Fri, 18 Mar 2016 00:00:00 +0100

Authors: Salmoiraghi S, Guinea Montalvo ML, Ubiali G, Tosi M, Peruta B, Zanghi' P, Oldani E, Boschini C, Kohlmann A, Bungaro S, Intermesoli T, Terruzzi E, Angelucci E, Cavattoni I, Ciceri F, Bassan R, Rambaldi A, Spinelli O PMID: 26992948 [PubMed - as supplied by publisher] (Source: Haematologica)

Clinical value to quantitate hematogones in Chinese childhood acute lymphoblastic leukemia by flow cytometry analysis

Thu, 17 Mar 2016 08:34:18 +0100

ConclusionThe strong independently prognostic impact indicated that the better HGs regeneration is a marker of better response to therapy. (Source: Clinical and Laboratory Haematology)

Pharmacokinetics of high-dose methotrexate in infants aged less than 12 months treated for aggressive brain tumors

Thu, 17 Mar 2016 00:00:00 +0100

Conclusions Our data suggest that a higher dose of MTX for the treatment of aggressive brain tumors in early infants had an acceptable pharmacokinetic profile. Greater attention must be used in the treatment of children weighing less than 4 kg. (Source: Cancer Chemotherapy and Pharmacology)

Novel TNF-related Apoptotic-inducing Ligand-based Immunotoxin for Therapeutic Targeting of CD25 Positive Leukemia

Wed, 16 Mar 2016 23:00:00 +0100

Abstract Background Human TNF-related apoptotic-inducing ligand (TRAIL) has been used successfully for targeted therapy of almost all cancers. Leukemia is the most common type of cancer in children, and despite the advances in therapeutic strategies, the survival rate in leukemia cases is very low. Overexpression of interleukin 2 receptor (IL2R) in hematological malignancies has been utilized to target leukemia. Here, we report an immunotoxin fusion construct of human IL2α and TRAIL for targeting leukemia. Aim Our aim was to develop an immunotoxin to target CD25+ leukemic cells. Methods Recombinant fusion construct comprising human IL2α and TRAIL114–281 was cloned, expressed an...

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Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia in Adults

Wed, 16 Mar 2016 23:00:00 +0100

Abstract The majority of adults with acute lymphoblastic leukemia will achieve a first complete remission (CR). However relapse is the most common cause of treatment failure. Outcomes after relapse remain poor, with long-term survival in the order of 10 %. Treatment decisions made at the time of first complete remission are thus critical to ensuring long-term survival. Allogeneic hematopoietic cell transplant (HCT) is effective at preventing relapse in many transplant recipients but is also associated with significant treatment related morbidity and mortality. Alternatively, ongoing systemic chemotherapy offers lower toxicity at the expense of increased relapse rates. Over the past decades, both the safety of transplant and the efficacy of non-transplant chemotherapy have improve...

Cellular protein plays important role in aggressive childhood cancer

Wed, 16 Mar 2016 04:07:58 +0100

UCLA scientists have uncovered how a cellular protein contributes to an aggressive form of leukemia prevalent in young children. The discovery is an important step forward in the effort to better understand and treat aggressive childhood leukemia. The study was published in the Journal of Clinical Investigation. “Certain subtypes of leukemia are very hard to treat and typically children with these subtypes have poor prognosis,” said Dr. Dinesh Rao, the study’s senior author and a member of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. “Pinpointing specific differences in how cancer cells function is critical in the development of targeted treatments, especially for these types of aggressive cancers that often recur and don’t respond well to...

An e13a3 BCR‐ABL1 fusion transcript in variant t(9;22;17)(q34;q11;q21)‐positive adult acute lymphoblastic leukemia

Wed, 16 Mar 2016 00:00:00 +0100

(Source: Clinical and Laboratory Haematology)

The Association Between Motor Skills and Academic Achievement Among Pediatric Survivors of Acute Lymphoblastic Leukemia

Wed, 16 Mar 2016 00:00:00 +0100

Conclusion These findings suggest that VMI is associated with aspects of math and reading achievement in leukemia survivors. These skills may be amenable to intervention. (Source: Journal of Pediatric Psychology)

An e13a3 BCR-ABL1 fusion transcript in variant t(9;22;17)(q34;q11;q21)-positive adult acute lymphoblastic leukemia.

Wed, 16 Mar 2016 00:00:00 +0100

Authors: Zhang X, Pan J PMID: 26991870 [PubMed - as supplied by publisher] (Source: International Journal of Laboratory Hematology)

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Clinical value to quantitate hematogones in Chinese childhood acute lymphoblastic leukemia by flow cytometry analysis.

Wed, 16 Mar 2016 00:00:00 +0100

CONCLUSION: The strong independently prognostic impact indicated that the better HGs regeneration is a marker of better response to therapy. PMID: 26991766 [PubMed - as supplied by publisher] (Source: International Journal of Laboratory Hematology)

Persistent Multiyear Control of Relapsed T‐Cell Acute Lymphoblastic Leukemia With Successive Donor Lymphocyte Infusions: A Case Report

Tue, 15 Mar 2016 16:08:01 +0100

We present the case of a now 9‐year‐old female in whom second haploidentical HSCT, followed by successive donor lymphocyte infusions in response to minimal residual disease reemergence, has led to 3+ years of ongoing disease control without graft versus host disease and excellent quality of life. (Source: Pediatric Blood and Cancer)

Developing "Care Assistant": A smartphone application to support caregivers of children with acute lymphoblastic leukaemia

Tue, 15 Mar 2016 00:00:00 +0100

Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. Caring for children with ALL is an uncommon experience for parents without medical training. They urgently need professional assistance when their children are recovering at home. This paper documents the process of developing an Android application (app) "Care Assistant" for family caregivers of children with ALL. Key informant interviews and focus group studies were used before programming the app. The key informants and focus group members included: caregivers of children with ALL, cancer care physicians and nurses, and software engineers. We found several major challenges faced by caregivers: limited access to evidence-based clinic information, lack of financial and social assistance, deficient communications ...

RNA-binding protein IGF2BP3 targeting of oncogenic transcripts promotes hematopoietic progenitor proliferation

Mon, 14 Mar 2016 21:19:02 +0100

Posttranscriptional control of gene expression is important for defining both normal and pathological cellular phenotypes. In vitro, RNA-binding proteins (RBPs) have recently been shown to play important roles in posttranscriptional regulation; however, the contribution of RBPs to cell specification is not well understood. Here, we determined that the RBP insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is specifically overexpressed in mixed lineage leukemia–rearranged (MLL-rearranged) B-acute lymphoblastic leukemia (B-ALL), which constitutes a subtype of this malignancy associated with poor prognosis and high risk of relapse. IGF2BP3 was required for the survival of B-ALL cell lines, as knockdown led to decreased proliferation and increased apoptosis. Enforced expression of...

LNK/SH2B3 regulates IL-7 receptor signaling in normal and malignant B-progenitors

Mon, 14 Mar 2016 21:19:02 +0100

Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk ALL commonly associated with alterations that affect the tyrosine kinase pathway, tumor suppressors, and lymphoid transcription factors. Loss-of-function mutations in the gene-encoding adaptor protein LNK (also known as SH2B3) are found in Ph-like ALLs; however, it is not clear how LNK regulates normal B cell development or promotes leukemogenesis. Here, we have shown that combined loss of Lnk and tumor suppressors Tp53 or Ink4a/Arf in mice triggers a highly aggressive and transplantable precursor B-ALL. Tp53–/–Lnk–/– B-ALLs displayed similar gene expression profiles to human Ph-like B-ALLs, supporting use of this model for preclinical and molecular studies. Preleukemic Tp53–/–Lnk–/– pr...

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Notch Activation in ALL Suppresses Hematopoiesis

Mon, 14 Mar 2016 00:00:00 +0100

More than half of T-cell acute lymphoblastic leukemia (T-ALL) patients harbor gain-of-function mutations in the intracellular domain of Notch1. Diffuse infiltration of the bone marrow commonly occurs in T-ALL and relapsed B-cell acute lymphoblastic leukemia patients, and is associated with worse prognosis. However, the mechanism of leukemia outgrowth in the marrow and the resulting biologic impact on hematopoiesis are poorly understood. Here, we investigated targetable cellular and molecular abnormalities in leukemia marrow stroma responsible for the suppression of normal hematopoiesis using a T-ALL mouse model and human T-ALL xenografts. We found that actively proliferating leukemia cells inhibited normal hematopoietic stem and progenitor cell (HSPC) proliferation and homing to the periva...

Molecular Analysis of Central Nervous System Disease Spectrum in Childhood Acute Lymphoblastic Leukemia

Mon, 14 Mar 2016 00:00:00 +0100

Treatment of the central nervous system (CNS) is an essential therapeutic component in childhood acute lymphoblastic leukemia (ALL). The goal of this study was to identify molecular signatures distinguishing patients with CNS disease from those without the disease in pediatric patients with ALL. We analyzed gene expression data from 207 pediatric patients with ALL. Patients without CNS were classified as CNS1, while those with mild and advanced CNS disease were classified as CNS2 and CNS3, respectively. We compared gene expression levels among the three disease classes. We identified gene signatures distinguishing the three disease classes. Pathway analysis revealed molecular networks and biological pathways dysregulated in response to CNS disease involvement. The identified pathways inclu...

Targeting leukemia stem cells: which pathways drive self-renewal activity in T-cell acute lymphoblastic leukemia?

Sun, 13 Mar 2016 18:01:02 +0100

Authors: Belmonte M, Hoofd C, Weng AP, Giambra V Abstract T-Cell acute lymphoblastic leukemia (t-all) is a malignancy of white blood cells, characterized by an uncontrolled accumulation of T-cell progenitors. During leukemic progression, immature T cells grow abnormally and crowd into the bone marrow, preventing it from making normal blood cells and spilling out into the bloodstream. Recent studies suggest that only discrete cell populations that possess the ability to recreate the entire tumour might be responsible for the initiation and propagation of t-all. Those unique cells are commonly called "cancer stem cells" or, in the case of hematopoietic malignancies, "leukemia stem cells" (lscs). Like normal hematopoietic stem cells, lscs are thought to be capable of self-renewal, dur...

Burden of Hospitalization in Relapsed Acute Lymphoblastic Leukemia.

Sat, 12 Mar 2016 07:38:02 +0100

CONCLUSIONS: Adults with Ph(-) relapsed B-cell precursor ALL had repeated and prolonged hospitalizations during chemotherapy treatment associated with extremely high costs. More effective, tolerable treatments are needed. LIMITATIONS: The key limitation was that the data source included only individuals from the health plans or the mid-large size employers in the MarketScan database. Patients who were not covered under these plans, or were only on Medicaid or only on Medicare, would not appear in our analysis. PMID: 26960412 [PubMed - as supplied by publisher] (Source: Current Medical Research and Opinion)

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Clinical Presentation of Inadvertent Intrathecal Vincristine Masquerading Guillain–Barre Syndrome

Sat, 12 Mar 2016 00:00:00 +0100

Abstract Vincristine, a potent chemotherapeutic agent, is highly neurotoxic. If given intrathecally by accident it is almost always fatal. We are reporting a 6 year old girl with acute lymphoblastic leukaemia in complete remission, who was given inadvertent intrathecal Vincristine instead of Methotrexate. She developed gradually progressive quadriplegia and respiratory paralysis requiring prolonged mechanical ventilation, initially mimicking Guillain–Barre Syndrome, both clinically and electro-physiologically. She also developed progressive encephalopathy. The clinical deterioration subsequently plateaued without any significant improvement and after more than 5 months, she finally expired. (Source: Indian Journal of Hematology and Blood Transfusion)

Immune checkpoint inhibitors enhance cytotoxicity of cytokine-induced killer cells against human myeloid leukaemic blasts

Thu, 10 Mar 2016 00:00:00 +0100

Abstract We studied whether blockade of inhibitory receptors on cytokine-induced killer (CIK) cells by immune checkpoint inhibitors could increase its anti-tumour potency against haematological malignancies. CIK cultures were generated from seven normal donors and nine patients with acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or multiple myeloma (MM). The inhibitory receptors B and T lymphocyte attenuator, CD200 receptor, lymphocyte activation gene-3 (LAG-3) and T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) were present at variable percentages in most CIK cultures, while cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed death-1 (PD-1) and killer cell immunoglobulin-like receptors (KIR2DL1/2/3) were expressed at low level in most ...

Dermatological lesions in acute lymphoblastic leukemia

Thu, 10 Mar 2016 00:00:00 +0100

BG SumathiIndian Journal of Cancer 2015 52(4):615-616 (Source: Indian Journal of Cancer)

Association of Macroeconomic Factors With Nonrelapse Mortality After Allogeneic Hematopoietic Cell Transplantation for Adults With Acute Lymphoblastic Leukemia: An Analysis From the Acute Leukemia Working Party of the EBMT

Thu, 10 Mar 2016 00:00:00 +0100

Conclusion. Both macroeconomic factors and the socioeconomic status of a country strongly influence NRM after alloHCT for adults with ALL. Our findings should be considered when clinical studies in the field of alloHCT are interpreted. Implications for Practice: Results of allogeneic hematopoietic cell transplantation (alloHCT) and other advanced oncological procedures may vary among countries and be related to various economic factors. This study, which included a homogenous population of patients with acute lymphoblastic leukemia, demonstrated significant associations of health care expenditure and the Human Development Index with nonrelapse mortality and overall survival after transplantation. The findings should be taken into account when clinical studies in the field of alloHCT are i...

Murine allogeneic CD19 CAR T cells harbor potent antileukemic activity but have the potential to mediate lethal GVHD

Thu, 10 Mar 2016 00:00:00 +0100

Acute lymphoblastic leukemia (ALL) persisting or relapsing following bone marrow transplantation (BMT) has a dismal prognosis. Success with chimeric antigen receptor (CAR) T cells offers an opportunity to treat these patients with leukemia-redirected donor-derived T cells, which may be more functional than T cells derived from patients with leukemia but have the potential to mediate graft-versus-host disease (GVHD). We, together with others, have previously demonstrated tumor-specific T-cell dysfunction in the allogeneic environment. Here, we studied CAR T-cell function following BMT using an immunocompetent murine model of minor mismatched allogeneic transplantation followed by donor-derived CD19-CAR T cells. Allogeneic donor-derived CD19-CAR T cells eliminated residual ALL with equal pot...

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Association of SHMT1 gene polymorphisms with the risk of childhood acute lymphoblastic leukemia in a sample of Iranian population.

Wed, 09 Mar 2016 18:00:02 +0100

In conclusion, our results suggest that the polymorphisms of SHMT1 gene are associated with childhood ALL risk in a sample of Iranian population. Further studies with larger sample sizes and different ethnicities are necessary to verify our findings. PMID: 26950450 [PubMed - in process] (Source: Cellular and Molecular Biology)

Corrigendum: Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia

Wed, 09 Mar 2016 00:00:00 +0100

Nature advance online publication 09 March 2016. doi:10.1038/nature16997 Authors: Zhengshan Chen, Seyedmehdi Shojaee, Maike Buchner, Huimin Geng, Jae Woong Lee, Lars Klemm, Björn Titz, Thomas G. Graeber, Eugene Park, Ying Xim Tan, Anne Satterthwaite, Elisabeth Paietta, Stephen P. Hunger, Cheryl L. Willman, Ari Melnick, Mignon L. Loh, Jae U. Jung, John E. Coligan, Silvia Bolland, Tak W. Mak, Andre Limnander, Hassan Jumaa, Michael Reth, Arthur Weiss, Clifford A. Lowell & Markus Müschen (Source: Nature AOP)

Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy [Pediatric Oncology]

Wed, 09 Mar 2016 00:00:00 +0100

Conclusion CRT does not have an impact on the risk of relapse in children with ALL treated on contemporary protocols. (Source: Journal of Clinical Oncology)

[Isolated unilateral cranial nerve palsy during childhood acute lymphoblastic leukemia treatment: What does it mean?]

Tue, 08 Mar 2016 00:00:00 +0100

Authors: Saumet L, Haouy S, Daien V, Hillaire-Buys D, Roessler J, Sirvent N PMID: 26968305 [PubMed - as supplied by publisher] (Source: Archives de Pediatrie)

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Obesity and Metabolic Syndrome Among Adult Survivors of Childhood Leukemia

Mon, 07 Mar 2016 00:00:00 +0100

Opinion statement Treatment-related obesity and the metabolic syndrome in adult survivors of childhood acute lymphoblastic leukemia (ALL) are risk factors for cardiovascular disease. Both conditions often begin during therapy. Preventive measures, including dietary counseling and tailored exercise, should be initiated early in the course of survivorship, with referral to specialists to optimize success. However, among adults who develop obesity or the metabolic syndrome and who do not respond to lifestyle therapy, medical intervention may be indicated to manage underlying pathology, such as growth hormone deficiency, or to mitigate risk factors of cardiovascular disease. Because no specific clinical trials have been done in this population to treat metabolic syndrome or its compo...

Nucleolar protein 4-like has a complex expression pattern in zebrafish embryos.

Sun, 06 Mar 2016 02:41:03 +0100

Authors: Borah S, Barrodia P, Swain RK Abstract The nucleolar protein 4-like (NOL4L) gene is present on chromosome 20 (20q11.21) in humans. Parts of this gene have been shown to fuse with RUNX1 and PAX5 in acute myeloid leukemia and acute lymphoblastic leukemia, respectively. The normal function of NOL4L in humans and other organisms is not well understood. The expression patterns and functions of NOL4L homologs during vertebrate development have not been reported. We sought to address these questions by studying the expression pattern of zebrafish nol4l during embryogenesis. Our data show that Znol4l mRNA is expressed in multiple organs in zebrafish embryos. The sites of expression include parts of the brain, spinal cord, pronephros, hematopoietic cells and gut. PMID: 26934290...

Endobronchial Aspergilloma: A Case Report

Sat, 05 Mar 2016 00:00:00 +0100

Publication date: Available online 4 March 2016 Source:Respiratory Medicine Case Reports Author(s): Aysel Sunnetcioglu, Selami Ekin, Remzi Erten, Mehmet Parlak, Ramazan Esen A 28-year-old male with B-cell acute lymphoblastic leukemia presented to our pulmonary clinic with progressive dyspnea, cough, hemoptysis, and fever. Diagnostic bronchoscopy revealed white masses at the entrance of the right middle lobe bronchus and distal to the right main bronchus. Histopathological examination of the biopsy specimen showed those masses to be hyphae of Aspergillus. (Source: Respiratory Medicine Case Reports)

Corrigendum: The Associations Between Maternal Factors During Pregnancy and the Risk of Childhood Acute Lymphoblastic Leukemia: A Meta‐Analysis

Fri, 04 Mar 2016 21:19:49 +0100

Because of the erroneous application of multiple publications, the conclusions of our recent paper (Pediatr Blood Cancer 2015;62:1162‐70) were not reliable. The corrected results show that coffee drinking during pregnancy was risk factor for childhood acute lymphoblastic leukemia (OR = 1.44, 95% confidence interval = 1.07–1.92). (Source: Pediatric Blood and Cancer)

Comment on: The Associations Between Maternal Factors During Pregnancy and the Risk of Childhood Acute Lymphoblastic Leukemia: A Meta‐Analysis

Fri, 04 Mar 2016 00:00:00 +0100

(Source: Pediatric Blood and Cancer)

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Pre-BCR signaling in precursor B-cell acute lymphoblastic leukemia regulates PI3K/AKT, FOXO1 and MYC, and can be targeted by SYK inhibition

Fri, 04 Mar 2016 00:00:00 +0100

Pre-BCR signaling in precursor B-cell acute lymphoblastic leukemia regulates PI3K/AKT, FOXO1 and MYC, and can be targeted by SYK inhibition Leukemia advance online publication, March 4 2016. doi:10.1038/leu.2016.9 Authors: S Köhrer, O Havranek, F Seyfried, C Hurtz, G P Coffey, E Kim, E ten Hacken, U Jäger, K Vanura, S O'Brien, D A Thomas, H Kantarjian, D Ghosh, Z Wang, M Zhang, W Ma, H Jumaa, K-M Debatin, M Müschen, L H Meyer, R E Davis & J A Burger (Source: Leukemia)

Fludarabine, idarubicin, and cytarabine regimen together with TKI followed by haploidentical hematopoietic stem cell transplantation, a success for relapsed Ph+ acute lymphoblastic leukemia

Fri, 04 Mar 2016 00:00:00 +0100

In this report, a case of relapsed Ph+ ALL was remedied by reinduction, and consolidation regimen of TKI and Flu+ Ara‐C+ IDA (FLAI) combination, followed by haploidentical SCT. Results suggest that FLAI together with TKI and subsequently with haploidentical SCT could be applied for relapsed Ph+ ALL. In this report, a case of relapsed Ph+ ALL was remedied by reinduction, and consolidation regimen of TKI and Flu+ Ara‐C+ IDA (FLAI) combination, followed by haploidentical SCT. Results suggest that FLAI together with TKI and subsequently with haploidentical SCT could be applied for relapsed Ph+ ALL. (Source: Clinical Case Reports)

UTX inhibition as selective epigenetic therapy against TAL1-driven T-cell acute lymphoblastic leukemia [Research Papers]

Fri, 04 Mar 2016 00:00:00 +0100

T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities, gene expression signatures, and prognoses. However, it remains unclear whether T-ALL subtypes differ at the functional level, and, as such, T-ALL treatments are uniformly applied across subtypes, leading to variable responses between patients. Here we reveal the existence of a subtype-specific epigenetic vulnerability in T-ALL by which a particular subgroup of T-ALL characterized by expression of the oncogenic transcription factor TAL1 is uniquely sensitive to variations in the dosage and activity of the histone 3 Lys27 (H3K27) demethylase UTX/KDM6A. Specifically, we identify UTX as a coactivator of TAL1 and show that it acts a...

An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a group for research in adult acute lymphoblastic leukemia study.

Fri, 04 Mar 2016 00:00:00 +0100

Authors: Bond J, Marchand T, Touzart A, Cieslak A, Trinquand A, Sutton L, Radford-Weiss I, Lhermitte L, Spicuglia S, Dombret H, Macintyre E, Ifrah N, Hamel JF, Asnafi V Abstract Gene expression studies have consistently identified a HOXA-overexpressing cluster of T-cell acute lymphoblastic leukemia, but it is unclear if this constitutes a homogeneous clinical entity, and the biological consequences of HOXA overexpression have not been systematically examined. We characterized the biology and outcome of 55 HOXA positive cases among 209 adult T-cell acute lymphoblastic leukemia patients uniformly treated during the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003 and -2005 studies. HOXA positive patients had markedly higher rates of an early thymic precursor-lik...

Laparoscopic Surgery for Acute Appendicitis in Children With Cancer.

Thu, 03 Mar 2016 17:20:02 +0100

DISCUSSION: Appendicitis is an important diagnosis in children with cancer, and laparoscopic appendectomy is safe and the procedure of choice. PMID: 26390529 [PubMed - indexed for MEDLINE] (Source: JSLS : Journal of the Society of Laparoendoscopic Surgeons)

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Re: Role of Electromagnetic Field Exposure in Childhood Acute Lymphoblastic Leukemia and No Impact of Urinary Alpha- Amylase - a Case Control Study in Tehran, Iran.

Thu, 03 Mar 2016 10:52:05 +0100

Authors: Dechent D, Driessen S PMID: 26925696 [PubMed - in process] (Source: Asian Pacific Journal of Cancer Prevention)

Multiplex RT-PCR Assay for Detection of Common Fusion Transcripts in Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia Cases.

Thu, 03 Mar 2016 10:52:05 +0100

CONCLUSIONS: Multiplex RT-PCR provides a rapid, simple and highly sensitive method to detect fusion transcripts for prognostic and risk stratification of ALL and CML patients. PMID: 26925663 [PubMed - in process] (Source: Asian Pacific Journal of Cancer Prevention)

Survival From Childhood Hematological Malignancies in Denmark: Is Survival Related to Family Characteristics?

Thu, 03 Mar 2016 00:00:00 +0100

ConclusionsFurther research is warranted to gain further knowledge on the impact of family factors on childhood cancer survival in other populations and to elaborate potential underlying mechanisms and pathways of those survival inequalities. (Source: Pediatric Blood and Cancer)

The Approach to Acute Lymphoblastic Leukemia in Older Patients: Conventional Treatments and Emerging Therapies

Thu, 03 Mar 2016 00:00:00 +0100

Abstract Acute lymphoblastic leukemia (ALL) among older adult patients presents significant clinical challenges. As opposed to pediatric populations, in whom long-term outcomes are markedly superior, those for adults remain grim. Nevertheless, younger adults with ALL have experienced a steady improvement in long-term survival in the last few decades. This is significantly different for older ALL patients, for whom long-term outcomes remain poor. Conventional chemotherapies are associated with sub-optimal outcomes and increased toxicity in this population. However, several emerging therapies, including antibody–drug conjugates, bi-specific engagers, and chimeric antigen receptor (CAR) T cells, have demonstrated much promise and are either incorporated into the existing therapeuti...

Cardioprotection and Safety of Dexrazoxane in Patients Treated for Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Advanced-Stage Lymphoblastic Non-Hodgkin Lymphoma: A Report of the Childrens Oncology Group Randomized Trial Pediatric Oncology Group 9404 [Pediatric Oncology]

Wed, 02 Mar 2016 00:00:00 +0100

Conclusion Dexrazoxane was cardioprotective and did not compromise antitumor efficacy, did not increase the frequencies of toxicities, and was not associated with a significant increase in second malignancies with this doxorubicin-containing chemotherapy regimen. We recommend dexrazoxane as a cardioprotectant for children and adolescents who have malignancies treated with anthracyclines. (Source: Journal of Clinical Oncology)

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Thiopurine biotransformation and pharmacological effects: contribution of oxidative stress.

Wed, 02 Mar 2016 00:00:00 +0100

Authors: Pelin M, De Iudicibus S, Londero M, Spizzo R, Dei Rossi S, Martelossi S, Ventura A, Decorti G, Stocco G Abstract Thiopurine antimetabolites are important agents for the treatment of severe diseases, such as acute lymphoblastic leukemia and inflammatory bowel disease. Their pharmacological actions depend on biotransformation into active thioguanine-nucleotides; intracellular metabolism is mediated by enzymes of the salvage pathway of nucleotide synthesis and relies on polymorphic enzymes involved in thiopurine catabolism such as thiopurine-S-methyl transferase. Moreover, thiopurines are catabolized in the liver also by xanthine oxidase, with potential production of reactive oxidative species and azathioprine is converted into mercaptopurine by a reaction with reduced glutat...

Amgen Submits Supplemental Biologics License Application For BLINCYTO® (Blinatumomab)

Tue, 01 Mar 2016 21:00:52 +0100

Filing Based on Phase 2 Study Showing BLINCYTO Provides Meaningful Therapeutic Benefits in Difficult-to-Treat Type of Pediatric Acute Lymphoblastic Leukemia THOUSAND OAKS, Calif., March 1, 2016 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for BLINCYTO® (blinatumomab) to include new data supporting the treatment of pediatric and adolescent patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). BLINCYTO, the first-and-only FDA-approved bispecific CD19-directed CD3 T cell engager (BiTE®) immunot... (Source: Amgen News Release)

Viridans Group Streptococcal Infections in Children After Chemotherapy or Stem Cell Transplantation: A 10-year Review From a Tertiary Pediatric Hospital

Tue, 01 Mar 2016 06:00:00 +0100

Abstract: Viridans Group Streptococci (VGS) are associated with high mortality rates in febrile neutropenia; yet there are no recent European pediatric studies to inform antimicrobial therapy. The aim of this study was to describe the characteristics, outcome, and resistance patterns of children with VGS bacteremia (VGSB) undergoing treatment of malignancy or hematopoietic stem cell transplant. Patients aged 0 to 18 years, admitted to a tertiary pediatric hemato-oncology center with VGSB, from 2003 to 2013, were included in the study. All data were collected retrospectively from medical records. A total of 54 bacteremic episodes occurred in 46 patients. The most common underlying diagnosis was relapsed acute lymphoblastic leukemia. Streptococcus mitis was the most frequent organism. A t...

Burkitt-Type Acute Lymphoblastic Leukemia With Precursor B-Cell Immunophenotype and Partial Tetrasomy of 1q: A Case Report

Tue, 01 Mar 2016 06:00:00 +0100

We report B-ALL with precursor B-cell immunophenotype and interesting partial tetrasomy of 1q. (Source: Medicine)

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Interleukin-15 deficiency promotes the development of T-cell acute lymphoblastic leukemia in non-obese diabetes mice with severe combined immunodeficiency

Tue, 01 Mar 2016 00:00:00 +0100

Authors: D Bobbala, R Kandhi, X Chen, M Mayhue, E Bouchard, J Yan, H Knecht, F Barabé, S Ramanathan & S Ilangumaran (Source: Leukemia)

Association of body mass index and survival in pediatric leukemia: a meta-analysis [Cancer]

Tue, 01 Mar 2016 00:00:00 +0100

Conclusion: Higher BMI at diagnosis is associated with poorer survival in children with pediatric ALL or AML. (Source: American Journal of Clinical Nutrition)

Porphyria cutanea tarda in a child with acute lymphoblastic leukemia

Tue, 01 Mar 2016 00:00:00 +0100

(Source: QJM)

Differentiation resistance through altered retinoblastoma protein function in acute lymphoblastic leukemia: in silico modeling of the deregulations in the G1/S restriction point pathway

Tue, 01 Mar 2016 00:00:00 +0100

As in many cancer types, the G1/S restriction point (RP) is deregulated in Acute Lymphoblastic Leukemia (ALL). Hyper-phosphorylated retinoblastoma protein (hyper-pRb) is found in high levels in ALL cells. Neve... (Source: BMC Systems Biology)

Cotreatment with Smac mimetics and demethylating agents induces both apoptotic and necroptotic cell death pathways in acute lymphoblastic leukemia cells

Tue, 01 Mar 2016 00:00:00 +0100

While the overall cure rate for children with ALL, the most common pediatric malignancy, nowadays is relatively high, patients with very high-risk or relapsed disease still have a poor prognosis [1,2]. Treatment failure is frequently due to defects of cancer cells in cell death pathways, which are critically required to mediate the antileukemic activity of cytotoxic therapies [3,4]. This emphasizes the need to develop novel treatment concepts that re-activate programmed cell death. (Source: Cancer Letters)

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Treatment and prognosis of childhood acute lymphoblastic leukemia on protocols ALL-BFM 90, 95 and ALL IC-BFM 2002: a retrospective single-center study from Olomouc, Czech Republic.

Tue, 01 Mar 2016 00:00:00 +0100

In conclusion, our center has demonstrated survival rates comparable to leading international study groups for childhood ALL over a substantial period of time. This has been achieved namely due to advances in diagnostics, excellent collaboration on regional, national and international level, quality assurance and high overall standard of care. The acquired experience has been crucial for current participation in the best performing Berlin-Frankfurt-Münster (BFM)-based international trials for childhood ALL. PMID: 26925793 [PubMed - as supplied by publisher] (Source: Neoplasma)

Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation.

Tue, 01 Mar 2016 00:00:00 +0100

Authors: van der Sluis IM, Vrooman LM, Pieters R, Baruchel A, Escherich G, Goulden N, Mondelaers V, de Toledo JS, Rizzari C, Silverman LB, Whitlock JA Abstract L-asparaginase is an integral component of therapy for acute lymphoblastic leukemia. However, asparaginase-related complications, including the development of hypersensitivity reactions, can limit its use in individual patients. Of considerable concern in the setting of clinical allergy is the development of neutralizing antibodies and associated asparaginase inactivity. Also problematic in the use of asparaginase is the potential for the development of silent inactivation, with the formation of neutralizing antibodies and reduced asparaginase activity in the absence of a clinically evident allergic reaction. Here we present...

Role of CXCR4-mediated bone marrow colonization in CNS infiltration by T-cell acute lymphoblastic leukemia.

Tue, 01 Mar 2016 00:00:00 +0100

Authors: Jost TR, Borga C, Radaelli E, Romagnani A, Perruzza L, Omodho L, Cazzaniga G, Biondi A, Indraccolo S, Thelen M, Te Kronnie G, Grassi F Abstract Infiltration of the central nervous system is a severe trait of T-cell acute lymphoblastic leukemia. Inhibition of CXC chemokine receptor 4 significantly ameliorates T-cell acute lymphoblastic leukemia in murine models of the disease; however, signaling by CXC chemokine receptor 4 is important in limiting the divagation of peripheral blood mononuclear cells out of the perivascular space into the central nervous system parenchyma. Therefore, Inhibition of CXC chemokine receptor 4 potentially may untangle T-cell acute lymphoblastic leukemia cells from retention outside the brain. Here, we show that leukemic lymphoblasts massively inf...

Altered expression of autophagy‐related genes might contribute to glucocorticoid resistance in precursor B‐cell type acute lymphoblastic leukemia

Tue, 01 Mar 2016 00:00:00 +0100

ConclusionsOur data imply that GC sensitivity might depend on the expression of several genes involved in regulation and execution of autophagy in a way that key autophagy inducers are downregulated while inhibitors of autophagy are upregulated in GC‐resistant cells.This article is protected by copyright. All rights reserved. (Source: European Journal of Haematology)

Haploidentical hematopoietic stem cell transplantation for paediatric high‐risk T‐cell acute lymphoblastic leukaemia

Tue, 01 Mar 2016 00:00:00 +0100

Abstract Paediatric HR T‐cell ALL demonstrates dismal prognosis with chemotherapy, and poor outcomes could be improved with allo‐SCT. HID‐SCT is an almost immediately available choice; however, few studies have focused on the outcomes of HID‐SCT for paediatric HR T‐ALL. Forty‐eight consecutive HR T‐ALL children who underwent HID‐SCT were included. Survival outcomes and factors predictive of outcomes were retrospectively analysed. Of the 48 patients, 35 were in CR1, 10 in CR2, and three in relapse. The cumulative incidence of grade 3/4 aGVHD was 10.4% and that of extensive cGVHD was 28.4%. The CIR at three yr was 30.8% and that of NRM at three yr was 14.7%. At a median follow‐up of 20.0 (range 2.5–124.2) months, the three‐yr LFS was 54.4%. Children who received transpl...

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Hospital discharge records as data source to monitor epidemiologic indicators of hematologic malignancies in Abruzzo.

Mon, 29 Feb 2016 10:49:02 +0100

CONCLUSIONS: Applying the cancer registries national rate, expected new diagnoses of HM in Abruzzo are about 620/year (46.4/100,000), compared to HDR estimates of 461 and 791/year (primary/all diagnoses fields: 58%). Since this percentage varies between 35% and 82%, our findings on the 2 methods seem useful for a validation process in the starting Cancer Registry. PMID: 26917409 [PubMed - as supplied by publisher] (Source: Tumori)

DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T‐Cell Acute Lymphoblastic Leukemia

Mon, 29 Feb 2016 00:00:00 +0100

ConclusionsCIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making. (Source: Pediatric Blood and Cancer)

Haploidentical versus Matched-Sibling Transplant in Adults With Philadelphia-negative high-risk Acute Lymphoblastic Leukemia: A biologically phase 3 randomized study.

Mon, 29 Feb 2016 00:00:00 +0100

CONCLUSIONS: Haploidentical HSCT achieves outcomes similar to those of MSD-HSCT for Philadelphia-negative high-risk ALL patients in CR1. Such transplantation could be a valid alternative as post-remission treatment for high-risk ALL patients in CR1 lacking an identical donor. PMID: 26927664 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Increased regulatory T cells in acute lymphoblastic leukaemia patients.

Sun, 28 Feb 2016 12:16:02 +0100

Discussion Tregs in cancer are particularly significant in immunotherapy. The manipulation of the immune system to treat cancer has for a long time ignored regulatory mechanisms inducible or in place. In lymphoma studies, tumour-specific mechanisms that are unlike conventional methods in the induction of Tregs have been hypothesized. In addition, tumour-infiltrating Tregs may present different profiles from peripheral blood pictures. Tregs will continue to be dissected to reveal its mysteries and their impact on clinical significance. PMID: 26907959 [PubMed - as supplied by publisher] (Source: Hematology)

Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution

Sun, 28 Feb 2016 00:00:00 +0100

Publication date: Available online 25 February 2016 Source:Cell Author(s): Boyang Zhao, Joseph C. Sedlak, Raja Srinivas, Pau Creixell, Justin R. Pritchard, Bruce Tidor, Douglas A. Lauffenburger, Michael T. Hemann The prevailing approach to addressing secondary drug resistance in cancer focuses on treating the resistance mechanisms at relapse. However, the dynamic nature of clonal evolution, along with potential fitness costs and cost compensations, may present exploitable vulnerabilities—a notion that we term “temporal collateral sensitivity.” Using a combined pharmacological screen and drug resistance selection approach in a murine model of Ph+ acute lymphoblastic leukemia, we indeed find that temporal and/or persistent collateral sensitivity to non-classical BCR-ABL1 ...

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Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC)

Sun, 28 Feb 2016 00:00:00 +0100

Publication date: Available online 27 February 2016 Source:The Lancet Haematology Author(s): Erin L Marcotte, Thomas P Thomopoulos, Claire Infante-Rivard, Jacqueline Clavel, Eleni Th Petridou, Joachim Schüz, Sameera Ezzat, John D Dockerty, Catherine Metayer, Corrado Magnani, Michael E Scheurer, Beth A Mueller, Ana M Mora, Catharina Wesseling, Alkistis Skalkidou, Wafaa M Rashed, Stephen S Francis, Roula Ajrouche, Friederike Erdmann, Laurent Orsi, Logan G Spector Background Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be establish...

Successful use of palifermin following severe anaphylaxis to pegaspargase in a pediatric patient with acute lymphoblastic leukemia

Sat, 27 Feb 2016 00:00:00 +0100

We report a case in which a child with very high-risk ALL having experienced severe anaphylaxis with pegaspargase was later successfully treated with palifermin during stem cell transplant conditioning. (Source: Journal of Oncology Pharmacy Practice)

Secondary thrombotic microangiopathy in two patients with Philadelphia-positive hematological malignancies treated with imatinib mesylate

Sat, 27 Feb 2016 00:00:00 +0100

In this study, we describe two patients with Philadelphia chromosome-positive hematological malignancies who presented with secondary thrombotic microangiopathy that was most likely linked to the use of imatinib. Other potential causes of thrombotic microangiopathy were discarded, and the predisposing role of some comorbidities and potential short or long-term drug–drug interactions was assessed. The clinical and biological data were more indicative of atypical secondary hemolytic uremic syndrome in one of the cases and of secondary thrombotic microangiopathy with renal and cardiac impairment in the other, which is also categorized as secondary hemolytic uremic syndrome. The outcome was favorable after imatinib discontinuation and the treatment of severe cardiac and renal failures. (...

Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in pregnancy

Sat, 27 Feb 2016 00:00:00 +0100

We report a woman treated with chemotherapy and imatinib mesylate who delivered a healthy baby at 30 weeks, and we discuss available data. (Source: Journal of Oncology Pharmacy Practice)

Potential association between pre-labor cesarean delivery and childhood leukemia IDed

Fri, 26 Feb 2016 05:00:00 +0100

(University of Minnesota Academic Health Center) A potential correlation between pre-labor cesarean delivery (PLCD) and acute lymphoblastic leukemia (ALL) could offer new targets for cancer prevention research, according to new research from the Masonic Cancer Center, University of Minnesota. (Source: EurekAlert! - Cancer)

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