Blast phase myeloproliferative neoplasm: Mayo-AGIMM study of 410 patients from two separate cohorts

Abstract

A total of 410 patients with blast phase myeloproliferative neoplasm (MPN-BP) were retrospectively reviewed: 248 from the Mayo Clinic and 162 from Italy. Median survival was 3.6 months, with no improvement over the last 15 years. Multivariable analysis performed on the Mayo cohort identified high risk karyotype, platelet count < 100 × 109/L, age > 65 years and transfusion need as independent risk factors for survival. Also in the Mayo cohort, intensive chemotherapy resulted in complete remission (CR) or CR with incomplete count recovery (CRi) rates of 35 and 24%, respectively; treatment-specified 3-year/5-year survival rates were 32/10% for patients receiving allogeneic stem cell transplant (AlloSCT) (n = 24), 19/13% for patients achieving CR/CRi but were not transplanted (n = 24), and 1/1% in the absence of both AlloSCT and CR/CRi (n = 200) (p < 0.01). The survival impact of AlloSCT (HR 0.2, 95% CI 0.1–0.3), CR/CRi without AlloSCT (HR 0.3, 95% CI 0.2–0.5), high risk karyotype (HR 1.6, 95% CI 1.1–2.2) and platelet count < 100 × 109/L (HR 1.6, 95% CI 1.1–2.2) were confirmed to be inter-independent. Similar observations were made in the Italian cohort. The current study identifies the setting for improved short-term survival in MPN-BP, but also highlights the limited value of current therapy, including AlloSCT, in securing long-term survival.

Allogeneic hematopoietic stem cell transplant overcomes the adverse survival effect of very high risk and unfavorable karyotype in myelofibrosis

“…The respective median (5‐year) survival rates in the latter study, in transplant‐age patients (age ≤70 years), were 1.3 years (6%), 3.2 years (30%), and 5.7 years (54%) . Furthermore, in another study of blast phase myeloproliferative neoplasm (MPN‐BP), the presence of VHR karyotype was shown to possibly undermine the value of HCT . The current study addresses the clinically important question of whether or not HCT can overcome the detrimental survival effect of VHR or unfavorable karyotype, in chronic phase MF.…”

Primary myelofibrosis: 2019 update on diagnosis, risk‐stratification and management

“…These mutations are mostly shared by patients with PV or ET . It is generally believed that driver mutations are essential for the MPN phenotype whereas the “other” mutations might contribute to disease progression and leukemic transformation …”

“…It is currently assumed that aberrant cytokine production by clonal cells and host immune reaction contribute to PMF‐associated bone marrow stromal changes, ineffective erythropoiesis, EMH, cachexia, and constitutional symptoms . Causes of death include leukemic progression that occurs in approximately 20% of patients but many patients also die of comorbid conditions including cardiovascular events and consequences of cytopenias including infection or bleeding …”

Successful Decitabine Treatment in Unfit, Elderly Patients with Acute Myeloid Leukemia following Chronic Myeloproliferative Neoplasm

“…The blastic phase of MPNs is a challenging therapeutic dilemma [2-5]. It is associated with poor treatment response and a median OS of 4 months, ranging from 3 to 10.2 months for patients receiving best supportive care or allogeneic SCT, respectively [3, 5]. Although some reports have suggested the useful role of hypomethylating agents to treat MPNs [7-11], no controlled clinical trials have been performed.…”

“…Approximately 5–10% of patients with a Ph-negative MPN progress into acute myeloid leukemia (AML) with a dismal outcome [2-4]. Treatment options for these patients are extremely limited [5-7], with only a minority suitable for intensive chemotherapy and/or allogeneic stem cell transplantation (SCT) [3]. Although a beneficial clinical role for hypomethylating compounds has been suggested [6-11], the effect of these agents in this difficult setting has not been clearly established.…”