Kazakhstan is the largest country in Central Asia. Hematological malignancies is a large socio-demographical problem for healthcare of Kazakhstan. There is a paucity of epidemiological data of ALL in Kazakhstan and Central Asia. Since 2010, patients with ALL are admitted to National Research Oncology Center (NROC) in the capital of Kazakhstan. At the same time, we have initiated first attempts of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with ALL in Kazakhstan and Central Asia. The first HSCT was performed in June 7, 2011. In this study, we analyzed incidence, death, and other epidemiological of ALL, based on electronic database of NROC.
Although, ALL in 80% cases occur in children and in 90% this disease is curable. Incidence of ALL in adults is more aggressive and less responsible to the treatment13.It is reported that ALL occurs mostly at age under 20 years old14. In our study, out of 210 patients only 2 patients were under 18 years old. ALL incidence was also shown to be related to the gender. Male patients develop ALL more frequently15. In our study, male patients also comprised the majority. In terms of age, female patients were, on average, 5 years older than males. Moreover, death rate in females was significantly higher. The latter finding can be for two reasons. First, our analysis showed that complete remission was reached significantly less in female than in male patients; second –female patients were elder to males, elder patients have higher death rate16.
According to the WHO, B cell ALL accounts for 75% of ALL cases. B cell ALL has worse survival rate in comparison to T cell ALL17. Similarly, our analysis showed that B cell ALL occurrence was significantly higher, however the mortality rate was identical in both types of ALL.
Established treatment approaches for ALL in adults has been adapted from pediatric protocols. According to the National Cancer Institute, patients aged from 15 to 39 years are defined as adolescents and young adults (AYA). Pediatric-inspired regimens of chemotherapy are recommended for AYA patients18. We have followed this recommendation in our hospital. However, we confess that, our patients were more likely be defined as young adults (< 60 years old), therefore eligible for BFM regimen.
The induction protocol type, either BFM or ALL KZ, showed a significant association with overall survival in patients, who underwent allo-HSCT, 68% and 32.4% respectively. BFM protocol is the most used therapy in pediatric patients. It widely known, that BFM leads to complete remission in 85–95% of cases in pediatric patients19.Our data proved that pediatric-inspired high-intensified chemotherapy correlates with better outcome after allo-HSCT. We found, that complete remission was significantly associated with better overall survival with and without stem cell transplantation.
Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the best treatment method for patients with ALL. It is widely accepted that patients with first complete remission are indicated for allo-HSCT20. In our center, patients with first or second remission in high-risk group were indicated for allo-HSCT, either HLA-identical or haploidentical. Our study revealed that survival probability in the group of patients, who underwent allo-HSCT was significantly better in comparison with those, who received chemotherapy only. The latter result is consistent with research outcomes worldwide. In a LALA-87 and LALA-94 study, overall survival of patients, who received HSCT and conventional- dose chemotherapy, was analyzed.
Significant superiority of HSCT was found in high risk group21 .In our study, we did not find any correlation between risk group and survival after HSCT. Previously, it was established that allo-HSCT can be performed only for eligible patients with available matched sibling donor (MSD)19. Recently, allo-HSCT is also performed from mismatched related donors (MMRD), mostly haploidentical22. Giebel et al. reported, that in their study 5% of all allo-HSCT were from mismatched related donor- haploidentical22.We have compared overall survival of patients after HSCT from matched and mismatched (haploidentical) donor. We did not find statistically significant difference in overall survival. Our data is consistent with previous reports from EBMT study. Recent modification and novel immunosuppressive agents23 can explain the phenomenon of successful haploidentical HSCT. EBMT showed that the probability of leukemia free survival (LFS) at 3 years after unmanipulated HSCT was 47%.In our study, five-year survival in MSD and haploidentical group was 47.7% and 30.8% respectively. The amount of transplanted cells and engraftment period had no impact on survival after allo-HSCT. Our analysis also revealed that survival probability in male patients is higher in comparison with females after HSCT. Among complications after HSCT, sepsis is the most common. Although, the mortality rate also depend on complication occurrence after allo-HSCT, we did not find a significant impact of sepsis on overall survival after HSCT, while aspergillosis development significantly worsened the outcome after HSCT.