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Among adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia, treatment with the bispecific anti-CD19 and anti-CD3 monoclonal antibody blinatumomab resulted in longer overall survival and higher remission rates than did chemotherapy. The prognosis for adults with newly diagnosed acute lymphoblastic leukemia (ALL) has improved over the past three decades. With the use of intensive chemotherapy regimens, complete remission rates are 85 to 90% and long-term survival rates are 30 to 50%. 1 – 4 Still, most adults with B-cell precursor ALL will have a relapse and will die from complications of resistant disease or associated treatment. Among adults with relapsed or refractory ALL, remission rates are 18 to 44% with the use of standard salvage chemotherapy, but the duration of remission is typically short. 5 – 10 A major goal in this population is to . . .

Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia characterized by leukemic blasts presenting myeloid and lymphoid markers. Here we report data from integrated genomic analysis on 31 MPAL samples and compare molecular profiling with that from acute myeloid leukemia (AML), B cell acute lymphoblastic leukemia (B-ALL), and T cell acute lymphoblastic leukemia (T-ALL). Consistent with the mixed immunophenotype, both AML-type and ALL-type mutations are detected in MPAL. Myeloid-B and myeloid-T MPAL show distinct mutation and methylation signatures that are associated with differences in lineage-commitment gene expressions. Genome-wide methylation comparison among MPAL, AML, B-ALL, and T-ALL sub-classifies MPAL into AML-type and ALL-type MPAL, which is associated with better clinical response when lineage-matched therapy is given. These results elucidate the genetic and epigenetic heterogeneity of MPAL and its genetic distinction from AML, B-ALL, and T-ALL and further provide proof of concept for a molecularly guided precision therapy approach in MPAL. Mixed phenotype acute leukemia (MPAL) is a rare leukemia that presents both myeloid and lymphoid markers on blasts. Here the authors perform genomic analysis to show MPAL involves genetic and epigenetic heterogeneity and is genetically distinct from AML, B-ALL, and T-ALL.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used to treat malignant hematological neoplasms and non-malignant hematological disorders. Approximately, 5000 allo-HSCT procedures are performed in China annually. Substantial progress has been made in haploidentical HSCT (HID-HSCT), pre-transplantation risk stratification, and donor selection in allo-HSCT, especially after the establishment of the “Beijing Protocol” HID-HSCT system. Transplant indications for selected subgroups in low-risk leukemia or severe aplastic anemia (SAA) differ from those in the Western world. These unique systems developed by Chinese doctors may inspire the refining of global clinical practice. We reviewed the efficacy of allo-HSCT practice from available Chinese studies on behalf of the HSCT workgroup of the Chinese Society of Hematology, Chinese Medical Association and compared these studies to the consensus or guideline outside China. We summarized the consensus on routine practices of all-HSCT in China and focused on the recommendations of indications, conditioning regimen, and donor selection.

This large trial of acute lymphoblastic leukemia in children aimed to determine whether intensive systemic and intrathecal chemotherapy could obviate the need for prophylactic central nervous system irradiation, which is associated with distressing late complications. The results show that, with meticulous monitoring of responses and toxic effects, it is possible not only to avoid cranial irradiation but also to improve the overall outcome. This large trial of acute lymphoblastic leukemia in children aimed to determine whether intensive systemic and intrathecal chemotherapy could obviate the need for prophylactic central nervous system irradiation. The results show that it is possible not only to avoid cranial irradiation but also to improve the overall outcome. Clinical trials have yielded 5-year event-free survival rates as high as 79 to 82% among children with acute lymphoblastic leukemia (ALL). 1 – 3 A major challenge is to reduce treatment-related late effects, which can occur in more than two thirds of long-term survivors. 4 In a growing proportion of patients, prophylactic cranial irradiation, once a standard treatment, is being replaced by intrathecal and systemic chemotherapy to reduce radiation-associated late complications such as second cancers, cognitive deficits, and endocrinopathy. 4 – 8 Two pediatric clinical trials tested whether prophylactic cranial irradiation could be completely omitted from treatment. 9 , 10 Although the cumulative risks of isolated central . . .

Identifying sociodemographic disparities in chemotherapy and hematopoietic cell transplantation (HCT) utilization for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) may improve survival for underserved populations. In this study, we incorporate neighborhood socioeconomic status (nSES), marital status, and distance from transplant center with previously studied factors to provide a comprehensive analysis of sociodemographic factors influencing treatments for ALL and AML. Using the California Cancer Registry, we performed a retrospective, population-based study of patients ≥15 years old with ALL (n = 3,221) or AML (n = 10,029) from 2003 through 2012. The effect of age, sex, race/ethnicity, marital status, nSES, and distance from nearest transplant center on receiving no treatment, chemotherapy alone, or chemotherapy then HCT was analyzed. No treatment, chemotherapy alone, or chemotherapy then HCT were received by 11%, 75%, and 14% of ALL patients and 36%, 53%, and 11% of AML patients, respectively. For ALL patients ≥60 years old, HCT utilization increased from 5% in 2005 to 9% in 2012 (p = 0.03). For AML patients ≥60 years old, chemotherapy utilization increased from 39% to 58% (p<0.001) and HCT utilization from 5% to 9% from 2005 to 2012 (p<0.001). Covariate-adjusted analysis revealed decreasing relative risk (RR) of chemotherapy with increasing age for both ALL and AML (trend p <0.001). Relative to non-Hispanic whites, lower HCT utilization occurred in Hispanic [ALL, RR = 0.80 (95% CI = 0.65-0.98); AML, RR = 0.86 (95% CI = 0.75-0.99)] and non-Hispanic black patients [ALL, RR = 0.40 (95% CI = 0.18-0.89); AML, RR = 0.60 (95% CI = 0.44-0.83)]. Compared to married patients, never married patients had a lower RR of receiving chemotherapy [ALL, RR = 0.96 (95% CI = 0.92-0.99); AML, RR = 0.94 (95% CI = 0.90-0.98)] or HCT [ALL, RR = 0.58 (95% CI = 0.47-0.71); AML, RR = 0.80 (95% CI = 0.70-0.90)]. Lower nSES quintiles predicted lower chemotherapy and HCT utilization for both ALL and AML (trend p <0.001). Older age, lower nSES, and being unmarried predicted lower utilization of chemotherapy and HCT among ALL and AML patients whereas having Hispanic or black race/ethnicity predicted lower rates of HCT. Addressing these disparities may increase utilization of curative therapies in underserved acute leukemia populations.

Minimal residual disease (MRD) after allogeneic stem cell transplantation (SCT) for Ph+ acute lymphoblastic leukemia (ALL) is predictive of relapse. Imatinib administration subsequent to SCT may prevent relapse, but the role of scheduling and its impact on outcome are not known. In a prospective, randomized multicenter trial, we compared the tolerability and efficacy of post-transplant imatinib administered either prophylactically (arm A; n =26) or following detection of MRD (arm B; n =29). Prophylactic imatinib significantly reduced the incidence of molecular recurrence after SCT compared with MRD-triggered imatinib (40% vs 69%; P =0.046). Median duration of PCR negativity was 26.5 and 6.8 months, respectively ( P =0.065). Five-year survival in both interventional groups was high (80 and 74.5%), despite premature discontinuation of imatinib in the majority of patients because of poor tolerability. Relapse probability was significantly higher in patients who became MRD positive ( P =0.017). In conclusion, post-transplant imatinib results in a low relapse rate, durable remissions and excellent long-term outcome in patients with BCR–ABL1 -positive ALL irrespective of whether it is given prophylactically or MRD-triggered. Reappearance of BCR–ABL1 transcripts early after SCT or at higher levels identifies a small subset of patients who do not benefit sufficiently from imatinib, and in whom alternative approaches should be explored.

Polyethylene glycol (PEG)-asparaginase (pegaspargase) is a key agent in chemotherapy for acute lymphoblastic leukemia (ALL), but recipients frequently experience allergic reactions. We hypothesized that by decreasing antibody-producing CD20-positive B cells, rituximab may reduce these reactions. Children and adolescents (aged 1–18 years) with newly diagnosed B-ALL treated on the St. Jude Total XVII study were randomized to induction therapy with or without rituximab on day 3 (cohort 1) or on days 6 and 24 (cohort 2). Patient clinical demographics, CD20 expression, minimal residual disease (MRD), rituximab reactions, pegaspargase allergy, anti-pegaspargase antibodies, and pancreatitis were evaluated. Thirty-five patients received rituximab and 37 did not. Among the 35 recipients, 16 (45.7%) experienced a grade 2 or higher reaction to rituximab. There were no differences between recipients and non-recipients in the incidence of pegaspargase reactions (P  >  0.999), anti-pegaspargase antibodies (P  =  0.327), or pancreatitis (P  =  0.480). CD20 expression on day 8 was significantly lower in rituximab recipients (P  <  0.001), but there were no differences in MRD levels on day 8, 15, or at the end of induction. Rituximab administration during induction in pediatric patients with B-ALL was associated with a high incidence of infusion reactions with no significant decrease in pegaspargase allergies, anti-pegaspargase antibodies, or MRD.

Patients with AML who were between 17 and 60 years of age were randomly assigned to receive induction therapy with the standard dose of daunorubicin or twice the standard dose; the two groups also received a standard dose of cytarabine. Rates of complete remission and overall survival were best in the high-dose group, especially among patients with a favorable or an intermediate cytogenetic risk profile. Patients with AML who were between 17 and 60 years of age were randomly assigned to receive induction therapy with the standard dose of daunorubicin or twice the standard dose. Rates of complete remission and overall survival were best in the high-dose group. The survival of patients with acute myeloid leukemia (AML) is affected by many variables, including therapy that induces complete remission and appropriate consolidation therapy. Currently, anthracycline plus cytarabine is the usual induction therapy for patients with AML. 1 The widely used intravenous combination of daunorubicin (at a dose of 45 mg per square meter of body-surface area), given daily for 3 days, and cytarabine (at a dose of 100 mg per square meter), given daily for 7 days, results in complete remission in 50 to 75% of patients. 1 , 2 Neither the addition of other drugs to daunorubicin and cytarabine 3 nor intensification . . .

In this study of unrelated-donor transplantation for hematologic cancers, survival was similar with bone marrow and peripheral-blood stem-cell grafts. However, graft failure was more common with the former, and chronic graft-versus-host disease with the latter. In the early days of allogeneic hematopoietic stem-cell transplantation, the only graft source available was bone marrow harvested from the pelvis of a donor under anesthesia. When studies showed that an increased dose of bone marrow cells correlated with more robust hematopoietic engraftment and lower mortality from infectious complications, transplantation centers began to use filgrastim-stimulated peripheral blood, which has a much higher content of blood progenitor cells than bone marrow, although there was concern that the higher T-cell content might increase the risk of graft-versus-host disease (GVHD). 1 – 5 Several large, randomized trials of transplantation between HLA-identical siblings showed that peripheral-blood . . .

Purpose of ReviewRecent treatment advances in both acute myeloid leukemia and acute lymphoblastic leukemia have drastically improved outcomes for these diseases, but central nervous system (CNS) relapses still occur. Treatment of CNS disease can be challenging due to the impermeability of the blood–brain barrier to many systemic therapies.Recent FindingsThe diagnosis of CNS leukemia relies on assessment of clinical symptoms, cerebrospinal fluid sampling for conventional cytology and/or flow cytometry, and neuroimaging. While treatment of CNS leukemia with systemic or intrathecal chemotherapy and/or radiation can be curative in some patients, these modalities can also lead to serious toxicities. In the modern era, prophylaxis with intrathecal chemotherapy is the most important strategy to prevent CNS relapses in high risk patients.SummaryAccurate risk stratification tools and the use of risk-adapted prophylactic therapy are imperative to improving the outcomes of patients with acute leukemias and preventing the development of CNS leukemia.