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Background Treatment of acute lymphoblastic leukemia (ALL) in adolescent and young adult (AYA) patients using traditional adult chemotherapy protocols give low overall survival (OS) rates. Data are growing regarding the use of pediatric-inspired chemotherapy protocols in AYA patients with improvement in OS. Patients and Methods To assess efficacy and tolerability of using a pediatric-inspired protocol in AYA patients, we initiated our local prospective trial using a modified version of the Children’s Cancer Group 1900 protocol for newly diagnosed high-risk Philadelphia chromosome-negative ALL patients. Results A total of 40 patients were enrolled in the study (from 2015 to 2018). The median age was 18 years (range, 14-34 years). The complete remission rate after induction was 37 patients [93%] and after a median follow-up of 5 years, OS, disease-free survival (DFS), and event-free survival were 75%, 72%, and 60%, respectively. Use of this protocol was well tolerated with manageable toxicities. Pegylated asparaginase was given to all patients during the induction phase and was well tolerated. Conclusion The use of a pediatric-inspired protocol for high-risk AYA ALL patients was effective and well tolerated with improvement in OS and DFS compared with historical data using adult protocols in such populations.

Introduction Busulfan is often used in a myeloablative conditioning regimen at an IV dose of 12.8 mg/kg (BU4). A reduced intensity regimen using 6.4 mg/kg (BU2) is commonly used in older patients or those with comorbid diseases. Data on use of BU3 (9.6 mg/kg) based regimen are limited. At KFSHRC, the busulfan-based MAC regimen’s IV-BU dose is 12.8 mg/kg (BU4), but for those who do not tolerate the full MAC, BU can be reduced to 9.6 mg/kg (BU3). Objective To study the outcomes of hematological malignancy patients who received allo-HCT using BU3-based conditioning from matched related or unrelated donors. Methods A retrospective analysis of the KFSHRC-BMT Database for patients who received allo-HCT between October 2005 and December 2019. Results A total of 65 patients were identified: 47 AML (72.3%), 8 MDS (12.3%), 8 myelofibrosis (12.3%), and 2 CML (3.1%) patients. Median age was 52 years (16–66), and 35 (54%) were males. Pre-transplant status showed 57% were in CR1, 17% in CR2, and 3% not in CR. Fifty-seven (88%) patients received PBSC, 6 (9%) received BM source, and 2 (3%) received both PBSC and BM from HLA-matched related [N= 61 (93%)] or unrelated [N=4 (7%)] donors. Forty (61.5%) patients received Bu/Flu as a conditioning regimen, 14 (21.5%) received Bu/Cy, 7 (10.8%) received Bu/Flu/ATG, and 4 (6.2%) received Bu/Cy/ATG. GVHD prophylaxis consisted of cyclosporine and methotrexate for all patients. Fifty-two (80%) patients had comorbidities with comorbidity index between 1–2 in 29 (44.6%) patients and more than 2 in 23 (35.4%). Sixty-two (95%) patients engrafted; median ANC and platelet engraftment were 18 days. Acute GvHD grade II–IV and III–IV occurred in 29% and 14%, respectively. Chronic GvHD occurred in 55% and was extensive in 24% of patients. With median follow-up of 60.5 months, the 2 year- and 5 year-OS were 58.5% and 44.1% respectively. The 2 year- and 5 year-DFS were 52.9% and 44.5%, respectively. Cumulative incidence of relapse and NRM at 2 years were 29.5% and 17.4%, respectively. Day +100 TRM was 10.7%. Conclusions Allogeneic SCT using BU3-based regimen appears feasible to use in patients who are not suitable for a fully myeloablative (BU4) regimen. TRM, DFS, and OS rate were comparable to reports from studies using a BU4-based regimen, warranting prospective studies in these patients.

Azacitidine and decitabine are hypomethylating agents frequently used interchangeably to treat myeloid neoplasms in different settings. Azacitidine is metabolized intracellularly into decitabine. Hypomethylating agents work by inhibiting DNA methyltransferases, causing demethylation of aberrantly methylated promoter regions of genes involved in the pathogenesis of myeloid neoplasms. Azacitidine was the first agent approved by the US Food and Drug Administration for treatment of myelodysplastic syndrome in 2004, after which, the use of azacitidine in other myeloid neoplasms increased significantly. It is a well tolerated agent and can be safely administered in the outpatient setting, which makes it an attractive choice for patients as well as physicians. In this review we summarize the published literature about the use of azacitidine in myeloid neoplasms, and shed the light on some ongoing trials.