The natural history and treatment outcome of blast phase BCR-ABL- myeloproliferative neoplasms

Abstract

We analyzed the outcomes of 74 patients diagnosed with BCR-ABL(-) myeloproliferative neoplasms in blast phase receiving induction chemotherapy (55%), low-intensity therapy (16%), stem cell transplantation (SCT; 3%), or supportive care (26%). Median survival from the date of blastic transformation was 5 months. Patients receiving supportive therapy had a median survival of 6 weeks. Complete remission with or without blood recovery was achieved in 46% of patients receiving induction chemotherapy, but remissions were not durable with a median progression-free survival of only 5 months. Eight patients received SCT either as first therapy or after responding to antileukemia therapy. These patients had a markedly superior survival, with 73% alive at a median follow-up of 31 months. JAK2V617F kinetics were assessed in 16 patients: 0 of 4 negative patients became positive at transformation, and among 12 positive patients, 1 had an increase in JAK2V617F% at transformation, 7 had a substantial decrease, and 4 had stable levels. Myeloproliferative neoplasm blast phase is associated with a dismal prognosis. Responses to chemotherapy can be achieved but are not durable. Long-term survivors had all received SCT either as first therapy or in first remission.

Figure 1

Survival for 74 patients from the date of blast phase diagnosis. Median survival was 5 months and actuarial 1-year survival was 27%. Median follow-up was 14 months.

Figure 2

The effect of treatment strategy on survival. (A) Patients who received stem cell transplantation (SCT) as first therapy (n = 2) or in first response (n = 6) had the most favorable outcome, with actuarial survival of 73% at a median survivor follow-up of 31 months (range, 6-131 months). Survival was similar between patients receiving AML induction (median, 6 months) and low-intensity therapy (median, 7 months). Patients receiving supportive care only had a median survival of 6 weeks. (B) Survival analysis comparing SCT as first therapy or in first response (n = 8) with patients achieving complete response (CR) plus or minus blood recovery (CRi) who did not proceed to early SCT (n = 13), and patients who received antileukemia therapy but who did not achieve a CR/CRi (n = 32). Median survival was not reached, 13 months and 4 months, respectively.

Figure 3

Kinetics of the JAK2V617F mutation during progression to blast phase in a patient with primary myelofibrosis. Serial analysis of marrow blast percentage and JAK2V617F mutation load showed extinction of the JAK2V617F-bearing clone during blast phase progression. In this patient, the JAK2V617F and the blast phase clones were clearly independent disease processes.