Allogenic bone marrow Transplant in Acute leukemia

Approximately 23,000 HCTs are reported to the CIBMTR annually, and the number increases by about 5% per year.Outcome in patients with acute myeloid leukemia (AML) ranges from death within a few days of beginning treatment (treatment related mortality, TRM) to likely cure. The major reason patients are not cured is resistance to treatment, often manifested as relapse from remission, rather than, even in older patients, TRM, whose incidence is decreasing.A major decision in the treatment of AML is whether to recommend HSCT in a first complete remission (CR1). HSCT is effective but involves significant morbidity and mortality. At present, this decision is based largely on cytogenetic findings at diagnosis, which are currently the most important biologic prognostic factor in AML. Based on prospective and retrospective data, patients with high-risk cytogenetics have been considered candidates for HSCT, while chemotherapy is recommended for those with favorable cytogenetics. Knowledge of the pre-treatment mutation status of various genes has improved our ability to assign initial treatment and, of particular importance, knowledge of whether patients ostensibly in remission have measurable residual disease should influence subsequent management.Genetic abnormalities are powerful prognostic factors that have been used for 2017 ELN risk stratification in AML.Results from conventional cytogenetics, gene mutations including NPM1, RUNX1, FLT3, TP53, ASXL1, CEBPA and gene rearrangements screening including PML-RARA, CBFB-MYH11, RUNX1-RUNX1T1, BCR-ABL1 are currently being used in routine practice for risk stratification.Molecular techniques can be divided into real-time PCR and next generation sequencing (NGS) . PCR provides sensitivity of 10(−4) to 10(−6) but is limited to the 40%-50% of patients with the fusion transcripts RUNX1-RUNX1T1 (characteristic of t[8;21]), CBFB-MYH11 [inv 16] or t[16;16]) or with an NPM1 mutation. In contrast, NGS can, theoretically, be applied to all leukemia specific genetic aberrations.However, some genes are not suitable for MRD detection either because, although positive at diagnosis, may be negative at morphologic relapse (eg, FLT3) or because they are associated with age-related clonal hematopoiesis7 and, as such, may have arisen before development of AML.risk of relapse following HCT in people who have <5% morphologic blasts but are MFC positive pre-HCT is closer to that seen in people receiving HCT with > 5%blasts ( active AML ) than to people who are MFC negative pre HCT. Regarding PCR, Ivey at al. demonstrated the 15% of patients with intermediate-risk AML and pretreatment NPM mutations who were in presumed CR but remained NPM positive in blood after 2 cycles of induction therapy had an 86% cumulative incidence of relapse vs 34% for NPM without FLT3 mutations. Likewise, less than 3 log reduction in PCR transcripts for RUNX1-RUNX1T1 or CBFB-MYH11 after high-dose cytarabine consolidation was associated with a 3-year cumulative incidence of relapse of 54% vs 22% for patients with the presumably favorable CBF AML.Might accounting for MRD affect the recommendation for HCT in ELN adverse or intermediate but not favorable patients Specifically, it seems plausible the presence of MRD might be used to upstage, and the absence of MRD to downstage, the pretreatment ELN risk score, although it appears the influence of MRD status may be less in the ELN adverse risk group. More attention would be given the possibility of allogeneic HCT in upstaged patients and less in down-staged patients. For example, patients in the ELN 2017 favorable group pretreatment but who have MRD after 2 cycles of therapy, as assessed by MFC or PCR, have risk of morphologic relapse within 1-2 years of approximately 50%, not dramatically different than the 60% seen in patients initially in the ELN adverse group but who have no MRD after 2 cycles.Investigating the potential utility of using MRD to decide between transplant and nontransplant approaches, Zhu et al. assigned patients with t(8;21) who were PCR positive after two consolidation courses (high risk) to receive HCT while PCR negative patients (low risk) were to receive autologous HCT or further chemotherapy.High risk patients who received HCT had better outcomes than high risk patients who did not, while outcomes were similar in low risk patients regardless of whether they received HCT.Disease relapse after allogeneic HCT for AML is the most common cause of treatment failure and is associated with poor outcomes. Interventions aimed at preventing disease relapse may be more successful than treatment of overt disease relapse. Several interventions to prevent AML relapse after HCT have been explored, including use of hypomethylating agents, FLT3 receptor tyrosine kinase inhibitors (TKIs) , histone deacetylase inhibitors and donor cellular infusions . Hypomethylating agents are particularly interesting for its potential to enhance graft-versus leukemia effects and modulate graft-versus-host response. Small prospective studies have been performed to study the safety and efficacy of various FLT3 inhibitors and hypomethylating agents as a maintenance strategy; however many questions remain including identification of patients most likely to benefit, the ideal agent for use, duration, toxicities, and impact on immune reconstitution and graft-versus-host disease (GVHD).negative patients. Multivariate analysis indicated persistent NPM positivity in blood was the sole predictor of relapse and had similar effects in people with or