Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the clonal expansion of hematopoietic lymphoid progenitors. With new target therapies, the survival of adults with ALL has improved in the past few decades. Unfortunately, there are no large ALL patient series in many Latin American countries. Data from the Acute Leukemia Workgroup that includes five Mexico City referral centers were used. Survival was estimated for adult patients with ALL during 2009–2015. In total, 559 adults with ALL were included. The median age was 28 years; 67% were classified into the adolescent and young adult group. Cytogenetic information was available in 54.5% of cases. Of the 305 analyzed cases, most had a normal caryotype (70.5%) and Philadelphia‐positive was present in 16.7%. The most commonly used treatment regimen was hyper‐CVAD. In approximately 20% of cases, there was considerable delay in the administration of chemotherapy. Primarily refractory cases accounted for 13.1% of patients. At the time of analysis, 26.7% of cases had survived. The 3‐year overall survival was 22.1%. The main cause of death was disease progression in 228 (55.6%). Clinical and public health strategies are needed to improve diagnosis, treatment and survivorship care for adult with ALL. This multicentric report represents the largest series in Mexico of adult ALL patients in which a survival analysis and risk identification were obtained.

Alonso HC, et al. Blood Res. 2017 Mar;52(1):44-49. https://doi.org/10.5045/br.2017.52.1.44

Different criteria have been used to diagnose mixed-phenotype acute leukemia (MPAL), which has impacted the number of individuals diagnosed with this pathology. Better outcomes have been reported when using acute lymphoblastic leukemia (ALL)-type chemotherapy in the treatment of MPAL. We compared the outcome of 4 groups of patients with MPAL. Group 1 included patients diagnosed using the 2008/2016 World Health Organization (WHO) classification; group 2 included patients diagnosed using the European Group for the Immunological Characterization of Leukemias (EGIL) criteria; group 3 included patients diagnosed using either the EGIL or the 2008/2016 WHO criteria; and group 4 was comprised of patients diagnosed with MPAL using the EGIL classification only. We found a significantly worse disease-free survival (groups 1-4) and overall survival (OS) (groups 2 and 3) when comparing MPAL patients to other acute leukemia (AL) patients. A significantly better OS was obtained in patients (groups 2-4) treated with ALL-type chemotherapy compared to acute myeloid leukemia (AML)-type regimens. In light of these results, and because a trend (P=0.06) was found with regard to a better OS in group 4 when compared to other AL patients, an argument can be made that the 2008/2016 WHO classification is underpowered to diagnose all MPAL cases, potentially resulting in the suboptimal treatment of some individuals with AL.

Patients with acute leukemia can express aberrant markers, defined as antigens that are normally restricted to a different lineage. The reported significance and frequency of these markers is inconclusive. We assessed the frequency and impact of aberrant markers in patients with acute leukemia in a referral institution in Mexico City. We included 433 patients, diagnosed and treated between 2005 and 2015 in our institution. Aberrant markers were expressed in 128 patients (29.6%); CD13 and CD33 were the most frequent aberrant markers in patients with acute lymphoblastic leukemia, while CD7 and CD19 were the most frequent in patients with acute myeloid leukemia. In the univariate analysis, the group with aberrant markers had a lower disease-free survival when compared with the aberrant-free group (8 vs. 13 months) (p = 0.03). Aberrant expression of CD10, CD20, and CD33 correlated with a worse outcome in a statistically significant manner. In the multivariate analysis, male gender, lymphoid lineage, secondary leukemia, high risk at diagnosis, and the presence of aberrant markers had a significantly negative impact on disease-free survival. The use of more aggressive treatment strategies could be considered in patients with acute leukemia and an aberrant expression of CD10, CD20, and CD33.

Primary graft failure (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). The optimal conditioning strategies for salvage HSCT in PGF remain undefined. We retrospectively analysed the outcomes of 19 patients with PGF who underwent a second HSCT between 2017 and 2024. Eleven patients (58%) received a novel one-day conditioning regimen comprising fludarabine, cyclophosphamide, alemtuzumab, and low-dose total body irradiation (Group I), while eight received a multi-day reduced intensity conditioning regimen (fludarabine-busulfan-2Gy total body irradiation) (Group II). All patients in Group I engrafted neutrophils compared to 50% in Group II. The cumulative incidence of neutrophil engraftment at day +28 was 82% in Group I and 50% in Group II (p=0.22). Platelet engraftment by day +28 was observed in 70% of patients in Group I and 54% in Group II (p=0.61). The median follow-up of survivors after second HSCT was 16.5 months (95% CI: 5.9-39). The 12-month overall survival (OS) was 53.3% in Group I and 37.5% in Group II (p=0.29). The day +100 non-relapse mortality (NRM) was 30.3% in Group I and 62.5% in Group II (p=0.12). No patients developed grade III-IV acute graft-versus-host disease (GvHD) or chronic GvHD. A one-day alemtuzumab-based conditioning regimen for salvage HSCT appears to be well tolerated and may be associated with improved engraftment, NRM, and OS when compared to the fludarabine-busulfan-2Gy total body irradiation regimen.

Female-to-male (F→M) sex-mismatched allogeneic hematopoietic stem cell transplantation (HSCT) is known to increase the risk of graft-versus-host disease (GvHD). We evaluated the impact of donor-recipient sex mismatch on GvHD incidence and assessed the efficacy of combined low-dose antithymocyte globulin (ATG) (2.5 mg/kg) and post-transplant cyclophosphamide (PTCy) as GvHD prophylaxis compared to calcineurin inhibitor-methotrexate/mycophenolate mofetil (CNI-MTX/MMF). We retrospectively analyzed 861 HSCT recipients, with AML as the predominant indication (82%). Among the cohort, 39% of transplants were sex-mismatched (M→F: 26%, F→M: 13%), while 61% were sex-matched (M→M: 42%, F→F: 19%). The primary outcomes were cumulative incidences of acute and chronic GvHD, relapse, and non-relapse mortality (NRM). F→M HSCT were associated with higher rates of grade II-IV acute GvHD at day +100 (42.2% vs. 27.0%, HR: 1.54; p<0.01) and chronic GvHD at 2 years (54.2% vs. 43.4%, HR: 1.33; p=0.05). In the overall cohort, ATG-PTCy was associated with a reduced risk of grade III-IV acute GvHD (HR: 0.42; p<0.01) and chronic GvHD (HR: 0.22; p<0.001) compared to CNI-MTX/MMF, without an increased risk of relapse (HR: 0.86, p=0.39) or NRM (HR: 0.59, p=0.35). A subgroup multivariable analysis of F→M recipients (n=114) confirmed a reduced risk of grade II-IV (HR: 0.48, p=0.05), grade III-IV acute GvHD (HR: 0.25; p=0.04), and chronic GvHD (HR: 0.33; p<0.01) with ATG-PTCy. F→M sex mismatch is associated with increased GvHD risk after HSCT. The combination of low-dose ATG and PTCy may help reduce GvHD in this high-risk group without an increase in disease relapse or NRM.