MIPSS70+ v2.0 predicts long-term survival in myelofibrosis after allogeneic HCT with the Flu/Mel conditioning regimen

Abstract

Although allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for myelofibrosis (MF), data are limited on how molecular markers predict transplantation outcomes. We retrospectively evaluated transplantation outcomes of 110 consecutive MF patients who underwent allo-HCT with a fludarabine/melphalan (Flu/Mel) conditioning regimen at our center and assessed the impact of molecular markers on outcomes based on a 72-gene next-generation sequencing panel and Mutation-Enhanced International Prognostic Scoring System 70+ v2.0 (MIPSS70+ v2.0). With a median follow-up of 63.7 months, the 5-year overall survival (OS) rate was 65% and the nonrelapse mortality (NRM) rate was 17%. In mutational analysis, JAK2 V617F and ASXL1 mutations were the most common. By univariable analysis, higher Dynamic International Prognostic Scoring System scores, unrelated donor type, and very-high-risk cytogenetics were significantly associated with lower OS. Only CBL mutations were significantly associated with lower OS (hazard ratio [HR], 2.64; P = .032) and increased NRM (HR, 3.68; P = .004) after allo-HCT, but CALR, ASXL1, and IDH mutations did not have an impact on transplantation outcomes. Patient classification per MIPSS70 showed worse OS for high-risk (HR, 0.49; P = .039) compared with intermediate-risk patients. Classification per MIPSS70+ v2.0 demonstrated better OS when intermediate-risk patients were compared with high-risk patients (HR, 0.291) and much lower OS when very-high-risk patients were compared with high-risk patients (HR, 5.05; P ≤ .001). In summary, we present one of the largest single-center experiences of Flu/Mel-based allo-HCT, demonstrating that revised cytogenetic changes and MIPSS70+ v2.0 score predict transplantation outcomes, and thus can better inform physicians and patients in making decisions about allo-HCT.

Primary myelofibrosis: 2021 update on diagnosis, risk‐stratification and management

“…Figure 2 outlines an operational treatment algorithm that is based on risk stratification according to MIPSS v2 . There is no evidence to support the value of specific drug therapy in asymptomatic patients with MIPSS v2 “low” or “very low” risk disease; similarly, previously published studies have suggested that such patients have more to lose, in terms of survival, from AHSCT, as opposed to conventional treatment that does not include transplant 46,47 . Therefore, observation alone is a reasonable treatment strategy in such patients, in the absence of treatment‐requiring symptoms, especially considering the current lack of disease‐modifying agents.…”

“…Therefore, observation alone is a reasonable treatment strategy in such patients, in the absence of treatment‐requiring symptoms, especially considering the current lack of disease‐modifying agents. AHSCT is the preferred treatment of choice for MIPSS v2 “high” or “very high” risk disease (Figure 2); 46,47 clinical trial participation is the most appropriate alternative in non‐transplant candidates. Symptom‐directed conventional therapy (discussed in more detail below) is reasonable to consider in treatment‐requiring MIPSS v2 intermediate‐risk disease and in higher risk patients who are not eligible for either AHSCT or investigational drug therapy (Figure 2).…”

Genetic factors rather than blast reduction determine outcomes of allogeneic HCT in BCR-ABL–negative MPN in blast phase

“…[15][16][17][18][19][20] Variant allele frequency (VAF) of mutations such as TP53 is much higher in MPN-BP than in chronic phase. 17,18,21 Cytogenetics and mutations in certain genes are predictive of HCT outcomes in myelofibrosis, [22][23][24] although their impact on outcomes of HCT in MPN-BP is unknown.…”

Reduced‐intensity conditioning allogeneic transplant with dual T‐cell depletion in myelofibrosis

“…Clinical prognostic scoring systems are necessary to predict post‐tranplant outcomes. The molecular and cytogenetic profile at diagnosis should be considered in order to better determine the optimal timing for transplant and post‐transplant outcome . MIPSS70+ v2.0 should be assessed prior to allo‐HSCT because it has been found to be predictive for long‐term survival in MF patients after allo‐HSCT …”

“…DIPSS and DIPSS‐Plus scores were calculated according to the blood work documented in the pretransplant assessment. MIPSS70 and MIPSS 70+ 2.0 scores were not calculated because mutational profiling studies for ASXL1, EZH2, SRSF2, U2AF1, and IDH were not routinely done in our center during the inclusion period of all the recipients in the study.…”