Allogeneic Stem Cell Transplantation for CML in Second Chronic Phase After Blast Crisis in the Tyrosine Kinase Inhibitor Era

Myeloid blast crisis (BC) is twice as common as the lymphoid type. In the pre-tyrosine kinase inhibitor (TKI) era there were suggestions that outcomes of lymphoid BC were better than myeloid with conventional chemotherapy. Achievement of second chronic phase (CP2) with low toxicity is more commonly seen with TKIs, but it is unknown if there is a difference in response or overall survival in terms of histology after allogeneic transplant (allo-HCT). We hypothesized patients (pts) with lymphoid BC would have superior outcomes versus myeloid BC after allo-HCT in CP2, and performed this analysis to test this hypothesis.

We retrospectively reviewed all pts that received an allo-HCT at MD Anderson from 1/2000 to 6/2011 for CML in CP2 after having had lymphoid (n=32) or myeloid (n=31) BC. 2 pts with biphenotypic BC were grouped with the myeloid cohort. Year 2000 was chosen to reflect the incorporation of TKI in clinical practice. Demographic and disease-related data were collected, as well as transplant-related covariates. Outcome of interest was survival, which was estimated using the Kaplan-Meier estimate, while survival comparisons between groups used the log rank test.

Median age at transplant was 40 and 38 years for lymphoid versus myeloid/biphenotypic, respectively. 87.5% (28/32) of lymphoid BC were diagnosed in CP while 12.5% (4/32) were diagnosed in BC initially. 60% (18/31) of myeloid/mixed pts were diagnosed in CP, while 20% (6/31) were diagnosed in accelerated phase and 20% (6/31) were diagnosed in BC. Transplant characteristics are summarized in Table 1. With a median follow-up of 24 months (range, 0.5–98 mo), 33 pts are alive (54%). Three-year survival was 55% versus 39% for lymphoid versus myeloid BC pts, respectively. (P=0.3; figure 1). Twenty-eight pts have died. Causes of death for pts with lymphoid BC post transplant were – acute GVHD 3/32(9%), and infection 2/32(6%). Causes of death in myeloid/biphenotypic BC allo-HCT pts were – acute GVHD 4/31(13%), chronic GVHD 3/31(10%), infection 1/31(4%), hemorrhage 1/31(4%) and graft rejection 1/31(4%). Death from persistent/relapsed disease was 22% and 22.5% in lymphoid and myeloid groups respectively, 7 pts in each cohort. Transplant related mortality in the first 100 days was 16% (5/32) for lymphoid group due to acute GVHD (3) and infection (2); 13% for myeloid group (4/31) due to acute GVHD (3) and hemorrhage (1). Disease characteristics, donor type, stem cell source or cytogenetic response prior to SCT (major or complete versus others) did not influence survival.

Figure 1

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Figure 1

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We did not confirm the hypothesis that lymphoid BC is associated with improved survival after alloHCT although there was a trend towards significance, perhaps due to a small sample size. Interestingly, we transplanted a higher number of lymphoid BC patients than would be expected by prevalence of this subtype of disease in the CML population at large. Approximately 45% of CP2 patients achieved long-term remission.

No relevant conflicts of interest to declare.