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1749 Induction Therapy Followed by Allogeneic Stem Cell Transplant for MPN Blast Phase: Outcomes From Mayo Clinic in ArizonaClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Poster I
Saturday, December 10, 2011, 5:30 PM-7:30 PM
Hall GH (San Diego Convention Center)

Chad Cherington, MD1*, James L. Slack, MD1, Jose F. Leis, MD, PhD1*, Roberta H. Adams, MD1*, Craig B. Reeder, MD2, Joseph R. Mikhael, MD2, John Camoriano, MD1, Pierre Noel, MD1, Raoul Tibes, MD, PhD1*, Jeffrey A. Betcher, R.Ph1*, Mary E Peterson, C.N.P1*, Meagan S. Higgins, C.N.P1*, Ginger Gillette-Kent, C.N.P1*, Lisa D. Tremblay, N.P1*, Jane J Olsen, N.P1* and Ruben A. Mesa, MD3

1Division of Hematology and Medical Oncology, Mayo Clinic in Arizona, Scottsdale, AZ
2Division of Hematology and Medical Oncology, Mayo Clinic Arizona, Scottsdale, AZ
3Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, AZ

BACKGROUND: We have previously reported that transformation of a myeloproliferative neoplasm (MPN) to acute leukemia or blast phase (MPN-BP) is accompanied by a median survival of 2.6 months (range 0-24.2 months) (Mesa et. al. Blood 2005) despite treatment. Allogeneic stem cell transplantation (ASCT) offers a potential for cure.  We reviewed 13 patients with MPN – BP who were candidates for ASCT, and 8 of those patients received ASCT after induction chemotherapy.

METHODS: Retrospective analysis of individuals who had a clear antecedent myeloproliferative neoplasm (essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF) (either primary (PMF) or post ET/PV)), transformed to MPN-BP, and were candidates for ASCT. Clinical characteristics at each phase of illness, therapy at each phase of illness, and outcome of ASCT were assessed.

RESULTS:

Patients (MPN details): Thirteen patients (8 male, 5 female, median age at diagnosis of MPN 42 years in those who underwent ASCT and 64 years in those who did not receive ASCT (combined median 53 years, range 26-70)) were identified who met the inclusion criteria, of whom 2 had ET, 4 PV, 2 Post-ET MF, 1 Post-PV MF and 4 PMF. Jak2-V617F mutation was present in 7 of 8 patients tested. Treatments used during the MPN phase included hydroxyurea in 9 (+ busulfan in 1 and + anagrelide in 1), and thalidomide/prednisone in 2 (two patients received no treatment prior to MPN-BP).

Patients (MPN-BP details): Transformation of an MPN to blast phase (from diagnosis of MPN) occurred after a median of 11 years in those who underwent ASCT and 8 years in non-ASCT (range 3 months to 30 years). At the time of MPN-BP diagnosis, 9 patients had an abnormal karyotype, 3 with complex karyotypes, 3 with trisomy 8 (sole abnormality), 1 with del(7q), 1 with del(13q). Leukemic induction consisted of standard anthracycline/cytarabine combination therapy (+/- etoposide), except for one patient received a study medication voreloxin. One patient who did not receive ASCT had remission after induction, but later expired from relapse, two expired soon after leukemic transformation, and two were too ill to receive induction. In the ASCT group (N=8), 5 patients achieved complete remission (CR) of their leukemia/return to MPN chronic phase (one of the five patients required a second induction to achieve CR), while 3 patients were considered primary induction failures due to persistence of > 5% blasts in the blood (2) or marrow (1) at the time of pre-transplant response assessment. The median time from diagnosis of MPN-BP to ASCT was 128 days.

ASCT Details and Outcomes: Patients (median age of 55 years at time of ASCT; range 44-73) underwent ASCT (all HLA identical, 3 matched unrelated donors, 5 matched sibling donors) with either reduced intensity conditioning (n=6) or fully myeloablative conditioning (n=2). After a median follow-up of 488 days (range 127 – 1206), 6 of 8 patients are alive and free of disease. MPN-BP recurred in two patients at day 69 and 77 post-transplant; both patients eventually died of progressive leukemia, one after a second transplant. Acute GVHD occurred in 3 patients (1 grade III, 2 grade II), and chronic GVHD in 4 (2 mild, 2 moderate).  All five patients who achieved CR (marrow and PB blasts < 5%) after induction therapy remain in continuous CR, while 2 of the 3 patients with evidence of persistent leukemia relapsed and died of MPN-BP. No patient died of transplant-related causes and all patients engrafted promptly.

CONCLUSION: Rapid induction followed by ASCT can offer a curative path for individuals with MPN-BP. Although limited by small numbers, our data suggest that leukemic clearance (marrow blast percentage < 5%) prior to ASCT is associated with improved outcome.

Disclosures: Mesa: Incyte: Research Funding; Lilly: Research Funding; SBio: Research Funding; Astra Zeneca: Research Funding; NS Pharma: Research Funding; Celgene: Research Funding.

*signifies non-member of ASH