Allogeneic hematopoietic cell transplantation in patients with chronic phase chronic myeloid leukemia in the era of third generation tyrosine kinase inhibitors: A retrospective study by the chronic malignancies working party of the EBMT

Abstract

Following the introduction of tyrosine kinase inhibitors (TKI), the number of patients undergoing allogeneic hematopoietic cell transplantation (allo‐HCT) for chronic phase (CP) chronic myeloid leukemia (CML) has dramatically decreased. Imatinib was the first TKI introduced to the clinical arena, predominantly utilized in the first line setting. In cases of insufficient response, resistance, or intolerance, CML patients can subsequently be treated with either a second or third generation TKI. Between 2006 and 2016, we analyzed the impact of the use of 1, 2, or 3 TKI prior to allo‐HCT for CP CML in 904 patients. A total of 323‐, 371‐, and 210 patients had 1, 2, or 3 TKI prior to transplant, respectively; imatinib (n = 778), dasatinib (n = 508), nilotinib (n = 353), bosutinib (n = 12), and ponatinib (n = 44). The majority had imatinib as first TKI (n = 747, 96%). Transplants were performed in CP1, n = 549, CP2, n = 306, and CP3, n = 49. With a median follow‐up of 52 months, 5‐year OS for the entire population was 64.4% (95% CI 60.9–67.9%), PFS 50% (95% CI 46.3–53.7%), RI 28.7% (95% CI 25.4–32.0%), and NRM 21.3% (95% CI 18.3–24.2%). No difference in OS, PFS, RI, or NRM was evident related to the number of TKI prior to allo‐HCT or to the type of TKI (p = ns). Significant factors influencing OS and PFS were > CP1 versus CP1 and Karnofsky performance (KPS) score > 80 versus ≤80, highlighting CP1 patients undergoing allo‐HCT have improved survival compared to >CP1 and the importance of careful allo‐HCT candidate selection.

Graft-versus-Host Disease Prophylaxis with Post- Transplantation Cyclophosphamide in Chronic Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation from an Unrelated or Mismatched Related Donor: A Comparative Study from the Chronic Malignancies Working Party of the EBMT (CMWP-EBMT)

“…established[29], and as in that study, we also found that CP1 remains a major prognostic factor. Compared to AdP-CML, CP1-CML is associated less frequently with additional chromosomal abnormalities, kinase domain BCR::ABL1 point mutations, or somatic cancer gene mutations, which have been linked to worse outcomes [30À32].…”

Continuous and differential improvement in worldwide access to hematopoietic cell transplantation: activity has doubled in a decade with a notable increase in unrelated and non-identical related donors

“…(29) Higher risk of mortality after allogeneic HCT among recipients with CML is reported for recipients of HCT at >1CP with observed >20% decreased survival, and with BCR-ABL1 mutations. (30,31) Strategies to predict TKI treatment resistance and optimal timing consideration for allogeneic HCT for young patients with CML-CP who manifest resistance to multiple TKI therapies should be followed as proposed in the ELN recommendations. (32) Donor/stem cell sources that contributed to improved access to allogeneic HCT showed different trends in each WHO region, but all regions were marked by an increase in the percentage of HCT from other related donors, the majority of whom were haploidentical donors.…”

Allogeneic transplantation for chronic myeloid leukemia: I'm not dead yet!

“…2 Times have changed, and the spectacular success of tyrosine kinase inhibitors has predictably and rightly consigned allogeneic transplant to the back burners of CML therapy. In this issue of the American Journal of Hematology, Chalandon et al 3 provide a retrospective analysis of nearly 1000 CML undergoing allogeneic transplant across many centers belonging to the European CML consortium. There are always limitations that come with such studies (selection bias of patients actually analyzed, not accounting for center-to-center differences in outcomes, etc.…”