Results of allogeneic hematopoietic stem cell transplantation in a mixed cohort of patients with Ph-positive acute lympho-blastic leukemia

Abstract

SummaryAdditional chromosomal abnormalities (ACA) are rather common in Ph+ acute lymphoblastic leukemia (ALL). However, their prognostic significance in the era of protein tyrosine kinase inhibitors and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still poorly known. A recent study [1] has shown that ACA exert unfavorable effect upon HSCT results in adult patients with Ph+ALL. Patients and methodsWe have performed a retrospective analysis of treatment results for a mixed cohort of the patients with Ph+ ALL, including 19 children (aged 5 -18 y.o.) and 46 adults (aged 19 -57 y.o.) who received allo-HSCT at our Institute over 2008 to 2015. Among sixty-five subjects with Ph+ ALL, the results of standard cytogenetic studies were available for 53 patients. ResultsThirty-three patients of 53 (51%) exhibited an isolated t(9;22) translocation. ACA were revealed in 20/53 patients (31%), including 13/53 (20%) subjects with 3 and more chromosome abnormalities. Chromosomes 1, 5, 7, 8, 9, 22 were most commonly affected with additional anomalies. Structural abnormalities attributable to ACA were imbalanced in 16 patients (80%), whereas only 4 patients (20%) showed balanced translocations. In a univariate analysis, significance was shown for the donor type (matched related and unrelated vs haploidentical, p=0.02), clinical stage at HSCT (1 st remission vs other stages, p=0.01, for EFS only), additional chromosomal abnormalities (ACA-negative vs ACA-positive, p=0.04, for OS only), and, in particular, complex chromosomal aberrations (<3 anomalies vs ≥3 anomalies, p=0.01, for OS only). According to multivariate analysis, the number of additional chromosomal abnormalities per karyotype (HR 2.79, р=0.01, for OS only) and clinical stage at HSCT (HR 2.15, 95% CI 1.13-4.09; р=0.01, for EFS only) are independent prognostic factors for clinical outcomes. ConclusionThe study has shown that complex chromosomal anomalies and the stage of disease at the moment of HSCT are independent prognostic factors in a mixed cohort of Ph+ ALL patients treated with hematopoietic stem cell transplantation. KeywordsAcute lymphoblastic leukemia, Ph 1 -positive, allo-HSCT, additional chromosomal abnormalities.

Achievements and Challenges in Allogeneic Hematopoietic Stem Cell Transplantation in Cytogenetically Unfavorable Acute Leukemias (Literature Review)

“…У 33 (53 %) из них транслокация t(9;22) (q34;q11) не была осложнена другими изменениями кариотипа. В то же время у 20 (31 %) пациентов имели место ДХА, причем у 13 (20 %) больных их было три и более на метафазу [60]. Чаще других ДХА выявлялись в хромосомах 1, 5, 7, 8, 9 и 22.…”

“…Итак, несмотря на то что у больных с Ph 1 + ОЛЛ имеют место грозные цитогенетические и молекулярные повреждения, осложняющиеся еще и ДХА [60], выполняемая в ремиссии и поддерживаемая с помощью ИТК аллоТГСК позволяет достигать 5-летней ОВ у большинства из них [53]. Более того, эти данные стали поводом для вопроса о возможности замены у части успешно леченных с помощью ИТК пациентов аллоТГСК на более простую аутоТГСК [59].…”