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

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 interindependent. 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

How to manage the transplant question in myelofibrosis

Allogeneic stem cell transplantation remains the only curative therapy for myelofibrosis. Despite advances in transplant, the morbidity and the mortality of the procedure necessitate careful patient selection. In this manuscript, we describe the new prognostic scoring system to help select appropriate patients for transplant and less aggressive therapies. We explore the advances in non-transplant therapy, such as with investigational agents. We review the blossoming literature on results of myeloablative, reduced intensity and alternative donor transplantation. Finally, we make recommendations for which patients are most likely to benefit from transplantation

Impact Of Conditioning Regimen, Donor Source, and DIPSS Score On Outcome Of Allogeneic Hematopoietic Stem Cell Transplantation For Myelofibrosis

Abstract To investigate impact of conditioning regimen, donor source, and Dynamic International Prognostic Scoring System (DIPSS) on outcome of allogeneic hematopoietic stem cell transplantation for myelofibrosis, we analyzed results in 388 patients transplanted between 1990 and 2011 in three major transplant centers (Essen, Germany: n = 63; Hamburg, Germany; n = 156; Seattle, USA: n = 169), including 216 male and 171 female patients, 18 – 79 (median 54) years old, with either primary (n = 283) or post ET/PV (n = 150) myelofibrosis who received myeloablative (n = 190), reduced intensity (n = 182), or non-myeloablative (n = 16) conditioning and were given stem cells from related (n = 156, including 152 HLA-identical siblings, 1 haplo-identical relative, and 3 identical twins ) or unrelated donors (n = 232; 175 were HLA-matched and 57 were HLA-mismatched). Stem cell source was bone marrow (n = 51) or peripheral blood (n = 337). According to DIPSS at time of transplantation patients were classified as low (n = 35), intermediate-1 (n = 106), intermediate-2 (n = 161), or high (n = 84) risk. The conditioning regimen consisted of busulfan 16 mg/kg and cyclophosphamide (n = 136), busulfan 10 mg//kg and fludarabine (n = 154), treosulfan-based (n = 26), TBI 12 Gy-based (n = 52), or low dose TB 2 Gy and fludarabine (n = 16), and melphalan 140 mg/m2 and fludarabine (n = 4). After a follow-up of 3.5 – 7.7 (median 5) years the 1-year non-relapse mortality (NRM) of the entire study cohort was 24% (95% CI: 20 – 28). In multivariate analysis significant factors for NRM were age as continuous variable (HR: 1.029; 95% CI: 1.011 – 1.048, p = 0.002), HLA mismatch (HR: 2.026; 95% CI: 1.318 – 3.113, p = 0.001), and TBI containing conditioning (HR 1.872; 95% CI: 1.198 – 2.926, p = 0.006). The cumulative incidence of relapse was 17% (95% CI: 13 – 21) at 5 years, negatively impacted by age as continuous variable (HR: 1.030; 95% CI: 1.003 – 1.057, p = 0.028), unrelated donors (HR: 0.560; 95% CI: 0.339 – 0.926, p = 0.024), and the use of ATG (HR: 2.425; 95% CI: 1.342 – 4.381, p = 0.003) or campath (HR: 3.257; 95% CI: 2.129 – 6.985, p &lt; 0.0001 The estimated 3 and 5 year overall survival for the study group was 62% (95% CI: 56 – 68%) and 59% (95% CI: 53 – 65%), respectively. Significant factors for 5-year survival in the univariate analysis were HLA-matched vs. mismatched donor (61% vs. 47%, p = 0.05), related vs. unrelated donors (65% vs. 54%, p = 0.03), high dose conditioning vs. RIC vs. NMA (58% vs. 61% vs. 32%, p = 0.04), non TBI vs. TBI containing conditioning regimens (62% vs. 42%; p = 0.001), and DIPSS score at transplantation (low 83% vs. intermediate-1 64% vs. intermediate-2 58% vs. high risk 45%; p &lt; 0.001). In the multivariate analysis for survival significant factors were age as continuous variable (HR: 1.027; 95% CI: 1.009 – 1.045; p = 0.004), DIPSS score: intermediate-1 (HR: 1.662, p = 0.3), intermediate-2 (HR: 2.069, p = 0.09), high (HR: 2.924, p = 0.02), and TBI-containing conditioning regimen (HR: 1.973; p &lt; 0.001). Conclusion This analysis of results in a large cohort of patients confirms a high success rate of allogeneic hematopoietic stem cell transplantation for myelofibrosis significantly impacted by DIPSS classification at the time of transplantation. In addition the analysis confirms the risk factors of patient age and donor HLA-mismatch. Furthermore, the data show similar results between RIC and MAC, but less favorable outcome with TBI containing conditioning, regardless of the dose of TBI. Novel approaches need to be developed, particularly for patients with more advanced disease. Contribution The authors NK and MD contributed equally. Disclosures: No relevant conflicts of interest to declare. </jats:sec