Induction-related mortality in adolescents and young adults with acute lymphoblastic leukemia in a resource-limited setting: do treatment-related complications create more impact than disease biology?

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a malignant clonal bone marrow disorder with a high mortality rate during the initial therapy. This retrospective study aimed to describe and analyze the risk factors and causes of induction-related mortality (IRM) in an adolescent and adult ALL population treated in a low- and middle-income country. METHODS: From 2009 to 2016, a total of 167 patients were included, of which 50.9% were male with a median age of 28 years. B-immunophenotype represented 97.6%, and high-risk cytogenetics were present in 23.3%. During induction therapy, 91% had at least 1 complication, most of which were infectious, with an IRM of 12%. RESULTS: Factors associated with increased mortality rate were central nervous system (CNS) status [CNS-3: hazard ratio (HR) 3.029; 95% confidence interval (CI), 0.79‒11.49; P =0.103 and CNS-2: HR, 9.98; 95% CI, 2.65‒37.65; P =0.001] and dialysis requirement (HR, 9.15; 95% CI, 2.44‒34.34; P =0.001). CONCLUSION: Our study confirms that ALL patients treated in resource-constrained settings have high rates of IRM, mainly attributed to advanced disease and high tumor burden at diagnosis.

Isolated Extramedullary Relapse in Acute Lymphoblastic Leukemia: What Can We Do Before and After Transplant?

• Isolated EMR is defined as the presence of clonal blasts in any tissue other than the medullary compartment with a bone marrow evaluation with less than 5% clonal blasts and a full donor chimerism. • Patients with iEMR have shown better survival outcomes when compared to BMR and EMR and in most cases it heralds a systemic relapse. • Risk factors for iEMR include: younger age, history of EMD, poor risk cytogenetics, advanced disease at HSCT, development of GVHD, and non-TBI based conditioning regimens. • Combination therapy, local and systemic, can achieve better remission rates in this subgroup of patients.

Outcomes and Challenges of Reproductive Health in Hematopoietic Stem Cell Transplantation Survivors.

Long-term therapy-related reproductive health side effects impact the quality of life of hematopoietic stem cell transplantation (HSCT) survivors. In this study, we evaluated the prevalence of gonadal dysfunction (GD) pre- and post-HSCT, analyzed factors associated with GD, and explored rates of fertility assessment (FA) and fertility preservation (FP) in a resource-limited setting. FA and outcomes of patients age ≤45 years undergoing HSCT between June 2000 and May 2018 were collected retrospectively. We included 213 patients with a median age of 26 years. Pre-HSCT FA was performed in 71.8%, with a GD rate of 17%. The rate of GD was not different between the sexes (females, 19.5% versus males, 16.1%; P = .616) and was only associated with increasing age. The rate of cryopreservation in the cohort was 3.3%. Almost one-half (47.7%) of post-HSCT patients completed FA and evidenced an increase in GD rate to 48.9%. Comparing pre-HSCT and post-HSCT GD rates, women had a significant increase (19.5% versus 81.4%; P < .001), whereas men did not (16.1% versus 20.4%; P = .76). These results were confirmed by a multiple imputation analysis accounting for missing data. Female sex, pre-HSCT cytotoxic therapy, myeloablative conditioning, and germ cell tumor (GCT) diagnosis were associated with post-HSCT GD. Reproductive health preservation can be positively impacted when FA and FP are prioritized at the initial diagnosis in HSCT candidates, particularly in women of older age and men with a diagnosis of GCT. The low FP success observed urges implementation of strategies that favor accessibility and improve quality of life of HSCT survivors in low- and middle-income countries.