We compared the efficacy and safety of eltrombopag (ELTR) combined with immunosuppressive therapy (IST) and IST alone in treatment-naïve children with severe (SAA) and very severe (vSAA) aplastic anemia. Ninety-eight pediatric patients were randomized to receive horse antithymocyte globulin and cyclosporin A with (n=49) or without (n=49) ELTR. The primary endpoint was the overall response rate (ORR) at 4 months. After 4 months, nonresponders were crossed over to the alternative group. In all patients, the ORR in ELTR+IST and IST groups was similar (65% vs. 53%, p=0.218); however, the complete response (CR) rate was significantly higher in ELTR+IST group (31% vs. 12%, p=0.027). In severity subgroups, the ORR was 89% vs. 57% (p=0.028) in favor of IST+ELTR in SAA, but it did not differ in patients with vSAA (52% vs. 50%, p=0.902). At 6 months after the crossover, 61% of initial ELTR(-) patients achieved a response compared to 17% of initial ELTR(+) patients (p=0.016). No significant difference in ELTR+IST and IST groups was observed in the 3-year OS (89% vs. 91%, p=0.673) or the 3-year EFS (53% vs. 41%, p=0.326). There was no unexpected toxicity related to ELTR. Adding ELTR to standard IST was well tolerated and increased the CR rate. The greatest benefit from ELTR combined with IST was observed in patients with SAA, but not in those with vSAA. The second course of IST resulted in a high ORR in initial ELTR(-) patients who added ELTR and had limited efficacy among patients who received ELTR upfront. Clinicaltrials.gov #NCT03413306.
Infants of the first year of life represent a unique group of patients with acute myeloid leukemia (AML). Materials and methods of the research: the characteristics of 492 patients with newly diagnosed AML aged 10 DoL-18 y/o who received intensive chemotherapy according to the AML-MM-2006 and AML-MRD-2018 guidelines in Apr. 2007-Apr. 2021 were analyzed. The analysis was carried out separately for infants (<1 y/o, 58/12%), young children (1-3 y/o, 99/20%) and children aged 3-18 y/o (335/68%). Results: the infant group was characterized by a higher incidence of hyperleukocytosis, extramedullary lesions, the predominance of monoblast/monocytic (63%) and megakaryoblast (24%) subvariants and chromosomal aberrations involving the 11q23 locus (KMT2A gene) (53%). “CBF leukemias” were virtually non-existent in infants (0% for t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 and 2% for inv(16)(p13.1q22)/CBF::MYH11) and the rates increased with age. Activating mutations in the FLT3 gene were extremely rare (2% vs. 13.5% in patients >/=3 y/o). Patients of the 1-3 y/o group were similar in morphological and cytogenetic characteristics to the infants’ group but had a smaller tumor mass and higher survival rates. The 5-year overall survival of infants was statistically significantly lower than in older patients, 52% vs. 67% (p<0.001), primarily due to high mortality prior to remission, which in its turn was caused by complications associated with hyperleukocytosis. Conclusions: given the vulnerability of this category of patients, it is reasonable to transfer them to larger medical facilities with extensive experience in the field in order to conduct the remission induction stage (especially cytoreduction) within the intensive care unit.
Introduction. Relapse of acute myeloid leukemia (AML) develops in children who received intensive chemotherapy and achieved the first complete remission (CR1). Only intensive anti-relapse chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HSCT) may lead to cure.Aim — to present the results of treatment of children with AML who relapsed after completion of treatment or while on therapy according to the AML-MM-2006 protocol.Materials and methods. The study included children with AML who relapsed after completion of treatment of the first-line therapy according to the AML-MM-2006 protocol. During the follow-up period (median — 4.6 years), 68 relapses were registered among 187 patients who reached CR1 (early — 36, late — 26; with a change of phenotype to ALL-6). The cumulative probability of relapse was 40 %. Four (6 %) patients with relapsed AML initially belonged to the group of standard, 33 (54 %) — of intermediate risk of relapse of AML and 25 (40 %) — to the group of high risk. Eleven (18 %) were patients with “CBF-leukemia”, 19 (31 %) — with rearrangements of the 11q23 (KMT2A gene). Fludarabine, high doses of cytarabine and idarubicin in 33 (80 %) or mitoxantrone in 8 (20 %) patients were used to induce the second complete remission (CR2) in 41 patients (66 %).Results. Out of 53 patients who received chemotherapy as a second induction therapy, CR2 was achieved in 30 patients (57 %) (in 9 — with early, in 21 — with late relapse) after chemotherapy courses; 2 patients died within 30 days of the start of CT; 21 patients were refractory to chemotherapy. HSCT after relapse was performed in 51 patients, mainly from a haploidentical donor. Twenty-five patients underwent HSCT in CR2, 26 — in the status of “active disease”. Among patients transplanted into CR2, the probability of relapse was 20 %, and the overall survival rate was 80 %. Among patients transplanted outside of CR2, the probability of achieving CR2 was 77 %, the probability of relapse was 50 % and overall survival (OS) 58 %. The probability of OS in the group as a whole reached 52 %. The most significant prognostic factors of an unfavorable outcome were early relapse, refractory course of relapse, M7 variant of AML, complex karyotype and rearrangements of the ETV6 gene, combined (“bone marrow + CNS damage + non-hematopoietic tissue”) relapse and relapse after HSCT performed in CR1.Conclusion. About 50 % of patients with relapses of AML can be cured with the help of high-dose chemotherapy and allo-HSCT.
Infants of the first year of life represent a unique group of patients with acute myeloid leukemia (AML). Materials and methods of the research: the characteristics of 492 patients with newly diagnosed AML aged 10 DoL-18 y/o who received intensive chemotherapy according to the AML-MM-2006 and AML-MRD-2018 guidelines in Apr. 2007-Apr. 2021 were analyzed. The analysis was carried out separately for infants (<1 y/o, 58/12%), young children (1-3 y/o, 99/20%) and children aged 3-18 y/o (335/68%). Results: the infant group was characterized by a higher incidence of hyperleukocytosis, extramedullary lesions, the predominance of monoblast/monocytic (63%) and megakaryoblast (24%) subvariants and chromosomal aberrations involving the 11q23 locus (KMT2A gene) (53%). “CBF leukemias” were virtually non-existent in infants (0% for t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 and 2% for inv(16)(p13.1q22)/CBF::MYH11) and the rates increased with age. Activating mutations in the FLT3 gene were extremely rare (2% vs. 13.5% in patients >/=3 y/o). Patients of the 1-3 y/o group were similar in morphological and cytogenetic characteristics to the infants’ group but had a smaller tumor mass and higher survival rates. The 5-year overall survival of infants was statistically significantly lower than in older patients, 52% vs. 67% (p<0.001), primarily due to high mortality prior to remission, which in its turn was caused by complications associated with hyperleukocytosis. Conclusions: given the vulnerability of this category of patients, it is reasonable to transfer them to larger medical facilities with extensive experience in the field in order to conduct the remission induction stage (especially cytoreduction) within the intensive care unit.
Первичные иммунодефицитные состояния (ПИДС)-редкие, генетически детерминированные нарушения иммунной системы. Чаще всего ПИДС проявляются инфекционными и аутоиммунными заболеваниями, но по мере увеличения продолжительности жизни больных с ПИД на фоне успешной терапии более значимым стал повышенный риск развития злокачественных новообразований (ЗН), прежде всего лимфом. Так, частота развития ЗН у пациентов с ПИДС составляет от 4 до 60%. В патогенезе развития лимфом при ПИДС важна роль онковирусов, однако имеют место и неинфекционные причины. Лимфомы при тяжелой комбинированной иммунной недостаточности (ТКИН) встречаются крайне редко и, как правило, представлены посттрансплантационными лимфопролиферативнми заболеваниями. Развитие истинных лимфом при ТКИН-крайне редкое событие. Мы приводим описание двух клинических случаев лимфом у детей с ТКИН с успешно проведенной непротокольной терапией лимфомы и последующей трансплантацией гематопоэтических клеток. Родители дали согласие на использование информации о ребенке в статье. ключевые слова: дети, тяжелая комбинированная иммунная недостаточность, лимфома, трансплантация гематопоэтических стволовых клеток
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