Long-Term Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Patients (pts) with Advanced Chronic Myeloid Leukemia (CML) Post Imatinib Failure.

Abstract

Allogeneic HSCT is a potentially curative treatment for pts with CML, and is effective after imatinib failure. We assessed the long-term results of HSCT in 92 consecutive pts with CML that had failed imatinib. Herein are the results of this review. Preparative regimens were reduced-intensity intravenous (IV) busulfan (Bu)-fludarabine (Flu) in 40 pts, IV Bu-cyclophosphamide in 39, Flu-melphalan in 6, and total body irradiation (TBI) based regimens in 7. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and mini-methotrexate 5 mg/m2. Donors were matched related in 49 (53%) and matched unrelated in 43 (47%). Prior to HSCT, 43 (47%) pts received imatinib therapy after interferon failure and 49 (53%) as frontline therapy. At the start of imatinib therapy, 48 (52%) pts were in chronic phase (CP), 23 (25%) in accelerated phase (AP), and 21 (23%) in blastic phase (BP). Median time on imatinib before HSCT was 15 months (range, 2–50). Best response to standard-dose imatinib was complete cytogenetic response (CCyR) in 32 (35%), partial (PCyR) in 10 (11%), minor (mCyR) in 10(11%), and complete hematologic response (CHR) in 25 (27%). Median age at HSCT was 43 years (range, 14–69). At HSCT, 30 pts were in CP (33%), 27 in AP (29%), 17 in BP (18%), and 18 in second CP (20%). Pts were followed for a median of 48 months (range 4–93) from HSCT. All but 2 pts engrafted within a median of 12 days (range, 5–20). Acute GVHD was observed in 42 (46%) pts (Grade I in 15, Grade II/III in 19, Grade IV in 8). Chronic GVHD was observed in 35 pts (extensive in 20). Chimerism studies at day 30 post HSCT were available in 81 pts and were 100% of donor type in 61 (75%) and mixed in 20 (25%). Seventy-nine pts (86%) responded (100% for pts in CP, 93% for pts in AP, 94% for pts in 2nd CP, 41% for pts in BP). Sixty-three pts achieved a major molecular response (MMR), complete (CMR) in 60; 16 achieved a CCyR only. Of the 30 pts in CP that responded, 2 (7%; both achieved a CMR) relapsed, 9 and 24 months post HSCT. Of the 25 pts in AP who responded, 8 (32%: 6 CMR, 2 CCyR) relapsed after a median of 13 months (range, 2–51) post HSCT. Of the 17 pts in 2nd CP who responded, 6 (35%; 2 CMR, 4 CCyR) relapsed. Of the 7 pts in BP who responded, 4 (57%; 4 CMR) relapsed after a median of 16 months (range, 3–45) post HSCT. At the last follow-up, 49 (53%) pts were alive and 43 (47%) died. Causes of death included progressive disease in 29, GVHD in 6, infections in 5, diffuse alveolar hemorrhage in 2, and unknown cause in 1. One and 2-year survival rates were 65% and 54%. The median survival for pts in BP, 2nd CP, and AP were, 4, 14, and 72 months, respectively. The median survival for pts in CP has not been reached. The estimated 1- and 4-year survival by disease stage is as follows : BP, 24% and 12%; 2nd CP, 67% and 49%; AP, 67% and 62%; CP 87% and 74%, respectively.In conclusion, HSCT remains an effective salvage strategy post imatinib failure, and disease stage at HSCT remains the stronger prognostic factor.Response to allogeneic HSCT (MMR, major molecular response; CMR, complete molecular response; CCyR, complete cytogenetic response)CPAP2nd CPBPN30271817MMR (%)83706741CMR (%)77676741CCyR (%)100939541Relapse rate (%)7323557Median survival (mos)NR721441- and 4-year survival (%)87 & 7467 & 6267 & 4924 & 12