Background

Despite the great clinical benefit from the advent of tyrosine-kinase inhibitors (TKIs) treatment for adult patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), allogeneic hematopoietic stem cells transplantation (allo-HSCT) does not appear to be dispensable, if the optimal long-term outcome is to be achieved. However, there are only few data reported on long-term survivors with Ph+ ALL, particularly for those not receiving pre-transplant TKIs in the conventional induction therapy.

In this retrospective analysis, we report on the long term outcomes of myeloablative allo-HSCT during the past 2 decades as single center experience. Data on the use of post-transplant TKIs and molecular monitoring for minimal residual disease are being collected to investigate their predictive role.

Patients and methods

Between 1989 and 2013, we collected 56 patients who underwent myeloablative allo-HSCT from HLA-identical siblings (n: 24), unrelated donors (n: 17), alternative donors (n: 15). Median age was 41 years (16-64). Disease phase at transplant was CR1 in 30 pts (53%), >CR1 in 26 pts. Pre-transplant TKI as part of induction therapy was given in 25 pts (44%). Conditioning regimen was TBI-based in 47 pts (83%) and chemotherapy-based in 9 pts. GVHD prophylaxis was given according to Center standard practice.

Results

Median follow-up was 67 months (1- 244). There were no cases of primary graft failure. Incidence of grade II-IV acute GVHD occurred in 31 pts (55%) and extensive chronic GVHD in 18 pts (32%). Transplant-related mortality was 35% at 2 years and 7 more patients died of non-relapse causes up to 12 years after transplant. The 10-year OS was 25% and significantly better for patients in CR1 vs. >CR1 (36% VS 14% - p=0,006). The 10-year DFS was 27% with no statistical difference for pts in CR1 vs. >CR1. Age at transplant and pre-transplant TKI did not affect the outcomes.

Conclusions

In this retrospective analysis over a 20-year time period, we show that approximately one-third of adult Ph+ ALL are cured if they undergo allo-HSCT in CR1. Therefore, we confirm that disease status at transplant has a major prognostic impact on clinical outcomes. The apparent lack of benefit of pre-transplant TKI exposure may be due to the retrospective nature of the analysis.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.

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