Acute Lymphoblastic Leukemia with t(4; 11)(q21; q23)/KMT2A-AFF1 Translocation: The Results of Allogeneic Hematopoietic Stem Cells Transplantation in Children and Adults

Abstract

Aim. The aim was to evaluate the results of the allogeneic hematopoietic stem cells transplantation (allo-HSCT) in children and adults with the most prognostically unfavorable acute lymphoblastic leukemia (ALL) with t(4; 11)(q21; q23)/KMT2A-AFF1 translocation. Methods. We examined 21 patients (12 females, 9 males) aged from 3 months to 48 years (median 18.9 years). The analysis of prognostic factors of overall (OS) and eventfree survival (EFS) after allo-HSCT in patients of different age groups with various clinical, transplantation and cytogenetic characteristics was performed. Allo-HSCT from HLA-compatible related and unrelated donors, as well as haploidentical allo-HSCT were performed in 4, 9 and 8 patients of age groups < 1 year, 1-18 years, and >18 years, respectively. In 10 (48 %) patients, allo-HSCT was performed in the first remission, in 2 (10 %) patients in the second remission, and in 9 (43 %) patients during the disease relapse. Results. In 8 (38 %) patients, the only chromosomal disorder was the translocation t(4; 11)(q21; q23). Additional changes in chromosomes were found in 11 (52 %) patients. In 8 (38 %) of them, 3 or more chromosomal abnormalities in the karyotype were found. According to the results of a univariant analysis, the OS and EFS were significantly different in patients with allo-HSCT performed in the first remission and at other stages of ALL (in the second remission and in relapse: p < 0.001 in both cases), as well as in patients with or without 3 or more cytogenetic disorders in the karyotype (p = 0.04 in both cases). The multivariant analysis showed that the only independent prognostic factor affecting the OS and EFS in ALL patients with t(4; 11) was the allo-HSCT, including the haploidentical procedure, during the first complete hematological and molecular remission (p = 0.002 and p = 0.0004, respectively). Conclusion. ALL with t(4; 11)/KMT2A-AFF1 was as an absolute indication for allo-HSCT in first remission, including children of < 1 year age group. Satisfactory results can be obtained with the use of haploidentical transplantation from the parents. This approach eliminates the search in the registers completely HLA-compatible donor and facilitates the treatment procedure.

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

“…В дополнение к этому в одной из наших последних работ [24] эффект аллоТГСК был оценен в смешанной возрастной группе, состоявшей из 21 больного в возрасте от 3 мес. до 48 лет (медиана 18,9 года).…”

“…В то же время результаты аллоТГСК у больных с прогностически неблагоприятными вариантами ОЛ до недавнего времени оценивались в объединенных когортах пациентов [14 -16]. Что касается многообещающих многоцентровых исследований по отдельным, в т. ч. редким, хромосомным вариантам ОЛ, они стали проводиться недавно [13, [17][18][19][20][21][22][23][24][25][26][27].…”

Efficacy of Chemotherapy in Acute Leukemia Patients Resistant to Previous Standard Treatment According to the Series Measurement of WT1 Gene Expression

“…Так, у ребенка в возрасте 12 мес. (№ 24) с диа-гнозом врожденного пре-В ОЛЛ с прогностически не-благоприятной транслокацией t(4;11), клинические и цитогенетические данные которого были недавно опубликованы [40], исходный уровень экспрессии гена WT1 равнялся 502 копиям/10 4 копий ABL. При этом содержание бластных клеток в костном мозге достигало 89 % (см.…”