Early post-transplantation factors predict survival outcomes in patients undergoing allogeneic hematopoietic cell transplantation for myelofibrosis.

Factors predicting allogeneic hematopoietic cell transplantation (HCT) outcomes in myelofibrosis in the early post-HCT period have not been defined thus far. We attempt to study such factors that can help identify patients at a higher risk of relapse or death. This retrospective study included 79 patients who underwent first HCT for myelofibrosis at three centers between 2005 and 2016. Univariate analysis showed that red blood cell (RBC) transfusion dependence (HR 9.02, 95% CI 4.0-20.35), platelet transfusion dependence (HR 8.17, 95%CI 3.83-17.37), 100% donor chimerism in CD33 + cells (HR 0.21, 95%CI 0.07-0.62), unfavorable molecular status (HR 4.41, 95%CI 1.87-10.39), normal spleen size (HR 0.42, 95%CI 0.19-0.94), grade ≥ 2 bone marrow fibrosis (vs. grade ≤ 1; HR 2.7, 95%CI 1.1-6.93) and poor graft function (HR 2.6, 95%CI 1.22-5.53) at day +100 were statistically significantly associated with relapse-free survival (RFS). RBC transfusion dependence and unfavorable molecular status were also statistically significant in the multivariate analysis. Patients in whom both of these factors were present had a significantly worse RFS when compared to those with one or none. While limited by a small sample size, we demonstrate the significance of transfusion dependence and molecular status at day +100 in predicting outcomes.

Assessment of Quality of Life following Allogeneic Stem Cell Transplant for Myelofibrosis.

Patient-reported outcomes (PROs) for patients with myelofibrosis (MF) have been well characterized, but little is known about quality of life (QoL) following allogeneic stem cell transplantation (allo-SCT). Medical data and PRO measures were collected before transplant and at day 30, day 100, and 1 year after allo-SCT. PRO measures include Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), Brief Fatigue Inventory, Global Assessment of Change, and Functional Assessment of Cancer Therapy-Bone Marrow Transplant. Forty-four patients who had baseline QoL and at least 1 post-transplant assessment were included. The median age of the patients was 62.5 years (range, 35 to 74 years). At baseline, the mean MPN Total Symptom Score was 28.0, and at day 30, day 100, and 1 year, it was 25.4, 32.3, and 24.3, respectively. However, in myeloproliferative neoplasm-specific symptoms, such as itching, night sweats, bone pain, and fever, a statistically significant improvement was observed for at least 1 time point following transplant. At day 30, 10 (26.3%) patients reported a little/moderately/very much better overall QoL since their transplant, and 26 (68.45%) had a little/moderately/very much worse QoL. At day 100, 10 (30.3%) reported better QoL and 19 (57.6%) reported worsening since transplant. By 1 year, 16 (61.5%) reported feeling better. Our study shows that there is very little change in symptom burden at 1 year following transplant in general, but MF-specific symptoms showed improvement. By 1 year, 61% felt that their QoL was better than it was before transplant.

Comparison of reduced intensity conditioning regimens used in patients undergoing hematopoietic stem cell transplantation for myelofibrosis.

The aim of this study is to compare clinical outcomes of patients who underwent allogeneic stem cell transplantation (HCT) for myelofibrosis with reduced intensity conditioning (RIC) using either Busulfan Fludarabine (BuFlu), Fludarabine Bis-chlorethyl-nitroso-urea/ carmustine Melphalan (FBM) or Fludarabine Melphalan (FluMel) regimens. Sixty-one patients were identified who underwent HCT with one of these RIC regimens. Overall survival (OS) was not different in the 3 groups. However, 100% donor chimerism was seen in more frequently at day +30 and day +100 in patients who received FBM or FluMel than BuFlu, in both CD3 and CD33 fractions. For instance, 100% donor chimerism in CD33 fraction was present in 100% patients in FBM cohort, 90% in FluMel cohort while 44% in BuFlu cohort at day +100. Acute graft-versus host disease, grade 2-4 and grade 3-4, was not statistically different in the 3 groups (BuFlu 47 and 35%, FBM 68 and 27%, FluMel 68 and 46%; p = 0.31 and 0.45). Relapses and non-relapse mortality was also not statistically significantly different. Our study shows similar OS with these 3 RIC regimens in myelofibrosis; although donor chimerism at day +30 and day +100 was better in patients who received FBM and FluMel.

Myeloid neoplasm with eosinophilia associated with isolated extramedullary FIP1L1/PDGFRA rearrangement.

Myeloid neoplasms with eosinophilia associated with PDGFRA rearrangement are very responsive to tyrosine kinase inhibitors (TKIs). Herein, we report a case of a 53-year-old man with eosinophilia and a well-differentiated extramedullary myeloid tumor with evidence of FIP1L1/PDGFRA rearrangement by fluorescent in situ hybridization in the extramedullary tissue. His bone marrow evaluation revealed a hypercellular marrow with eosinophilia but without evidence of a FIP1L1/PDGFRA rearrangement. The patient was treated with imatinib at a dose of 100 mg daily and responded with normalization of his peripheral eosinophil count. The case raises the possibility that an extramedullary myeloid tumor may represent a primary site for PDGFRA rearrangement, and highlights the importance of performing cytogenetic testing on extramedullary tissue. Detection of the chromosomal rearrangement is critical for initiation of effective targeted therapy that can improve patient outcomes.

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis with Prior Exposure to Janus Kinase 1/2 Inhibitors.

The impact of Janus kinase (JAK) 1/2 inhibitor therapy before allogeneic hematopoietic cell transplantation (HCT) has not been studied in a large cohort in myelofibrosis (MF). In this retrospective multicenter study, we analyzed outcomes of patients who underwent HCT for MF with prior exposure to JAK1/2 inhibitors. One hundred consecutive patients from participating centers were analyzed, and based on clinical status and response to JAK1/2 inhibitors at the time of HCT, patients were stratified into 5 groups: (1) clinical improvement (n = 23), (2) stable disease (n = 31), (3) new cytopenia/increasing blasts/intolerance (n = 15), (4) progressive disease: splenomegaly (n = 18), and (5) progressive disease: leukemic transformation (LT) (n = 13). Overall survival (OS) at 2 years was 61% (95% confidence interval [CI], 49% to 71%). OS was 91% (95% CI, 69% to 98%) for those who experienced clinical improvement and 32% (95% CI, 8% to 59%) for those who developed LT on JAK1/2 inhibitors. In multivariable analysis, response to JAK1/2 inhibitors (P = .03), dynamic international prognostic scoring system score (P = .003), and donor type (P = .006) were independent predictors of survival. Among the 66 patients who remained on JAK1/2 inhibitors until stopped for HCT, 2 patients developed serious adverse events necessitating delay of HCT and another 8 patients had symptoms with lesser severity. Adverse events were more common in patients who started tapering or abruptly stopped their regular dose ≥6 days before conditioning therapy. We conclude that prior exposure to JAK1/2 inhibitors did not adversely affect post-transplantation outcomes. Our data suggest that JAK1/2 inhibitors should be continued near to the start of conditioning therapy. The favorable outcomes of patients who experienced clinical improvement with JAK1/2 inhibitor therapy before HCT were particularly encouraging, and need further prospective validation.

Impact of race and ethnicity on outcomes and health care utilization after allogeneic hematopoietic cell transplantation.

Disparities in outcomes after hematopoietic cell transplant (HCT) are reported mostly by registry studies. We examined the association of self-reported race and ethnicity with outcomes and health care utilization after allogeneic HCT in a single center study. Clinical and socioeconomic data of 296 adult patients who underwent allogeneic HCT from November 2003 to October 2012 were analyzed. Survival was compared between non-Hispanic Whites (NHW) and minority patients using Cox proportional hazards regression. Some 73% of patients were NHW and 27% were racial/ethnic minority patients. More minority patients were younger and had lower socioeconomic status. Both unadjusted and adjusted overall and progression-free survival were comparable between the two groups. High risk disease, poor performance score and Medicare/Tricare were significant predictors of mortality. Health care utilization was comparable between the two groups. Homogeneity of medical care for allogeneic HCT may help overcome racial/ethnic disparities, but not those due to patients' primary insurance.

Financial burden in recipients of allogeneic hematopoietic cell transplantation.

Although allogeneic hematopoietic cell transplantation (HCT) is an expensive treatment for hematological disorders, little is known about the financial consequences for the patients who undergo this procedure. We analyzed factors associated with its financial burden and its impact on health behaviors of allogeneic HCT recipients. A questionnaire was retrospectively mailed to 482 patients who underwent allogeneic HCT from January 2006 to June 2012 at the Mayo Clinic, to collect information regarding current financial concerns, household income, employment, insurance, out-of-pocket expenses, and health and functional status. A multivariable logistic regression analysis identified factors associated with financial burden and treatment nonadherence. Of the 268 respondents (56% response rate), 73% reported that their sickness had hurt them financially. All patients for whom the insurance information was available (missing, n = 13) were insured. Forty-seven percent of respondents experienced financial burden, such as household income decreased by >50%, selling/mortgaging home, or withdrawing money from retirement accounts. Three percent declared bankruptcy. Younger age and poor current mental and physical functioning increased the likelihood of financial burden. Thirty-five percent of patients reported deleterious health behaviors because of financial constraints. These patients were likely to be younger, have lower education, and with a longer time since HCT. Being employed decreased the likelihood of experiencing financial burden and treatment nonadherence due to concern about costs. A significant proportion of allogeneic HCT survivors experience financial hardship despite insurance coverage. Future research should investigate potential interventions to help at-risk patients and prevent adverse financial outcomes after this life-saving procedure.

Reduced toxicity conditioning and allogeneic stem cell transplantation in adults using fludarabine, carmustine, melphalan, and antithymocyte globulin: outcomes depend on disease risk index but not age, comorbidity score, donor type, or human leukocyte antigen mismatch.

Although reduced-intensity conditioning has become standard of care for patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation (HCT), the optimum regimen has yet to be defined, and may depend on pretransplantation patient- and/or disease-specific risk factors. We report here results in 100 adults, ages 18 to 69, with high-risk hematologic malignancy who received conditioning with fludarabine, carmustine, melphalan, and rabbit antithymocyte globulin (FBM-A). Outcomes were stratified using the disease risk index (DRI) as published by Armand et al. (Blood 2012;120:905-913). Median age was 56, and patients were ineligible for standard myeloablative conditioning because of age, organ dysfunction, or prior autologous HCT. Patients underwent transplantation for myeloid (acute myelogenous leukemia, n = 40; myelodysplastic syndrome, n = 24; myelofibrosis, n = 13; other myeloid, n = 2) or lymphoid (acute lymphoblastic leukemia, n = 8; non-Hodgkin lymphoma, n = 8; Hodgkin lymphoma, n = 4, chronic lymphocytic leukemia, n = 1) malignancy. Donors were related in 26 patients (22 matched, 4 mismatched at 1 antigen) and unrelated in 74 (mismatched at 1 or 2 HLA loci in 33); grafts were peripheral blood stem cells in 97 patients, bone marrow in 2, and double cord in 1. According to the DRI, 68 patients were classified as low (n = 1) or intermediate risk (n = 67), and 32 were classified as high (n = 28) or very high risk (n = 4). With a median follow-up of surviving patients of 18 months, the Kaplan-Meier estimate of overall survival at 2 years for patients in the low/intermediate risk group is 80%, compared with 66% in the high/very high group (P = .11). Two-year cumulative incidence of relapse and nonrelapse mortality in the low/intermediate group are 9.9% and 15%, versus 25% and 19% in the high/very high group (respective P values .07 and .81). The cumulative incidence of acute graft-versus-host (GVHD) grades III to IV at 100 days was 8.1%, and the incidence of National Institutes of Health-defined moderate to severe chronic GVHD was 22% at 2 years. No deaths were attributable to chronic GVHD. Survival was not influenced by age, hematopoietic comorbidity index score, donor type, donor gender, or presence of mismatch. We conclude that FBM-A is an effective and safe conditioning regimen for adults up to age 69 with hematologic malignancies who have low-, intermediate-, or high-risk scores according to the DRI.

Allogeneic stem cell transplantation for myeloproliferative neoplasm in blast phase.

The prognosis for patients with Philadelphia-negative myeloproliferative neoplasms (MPN) who evolve into acute myeloid leukemia (AML) or blast phase (MPN-BP) is extremely poor. Although allogeneic stem cell transplantation (allo-SCT) is considered potentially curative, very few patients have been reported who have undergone allo-SCT for MPN-BP; therefore the success rate remains unknown. In a retrospective review, we identified 13 patients with an MPN transformation to blast phase after a median 9 years (range 5 months to 30 years); 8 (median age 55) continued to allo-SCT within 6 months. Induction chemotherapy cleared blood/marrow blasts in 60% (6/10) (2 declined therapy, 1 had early death). At the time of allo-SCT, 5/8 patients were in complete remission (CR) of their leukemia or had returned to MPN chronic phase (CP), 2 had residual blood blasts and 1 was refractory with >5% marrow blasts. At follow-up (median 20.3 months), 6 patients are alive in CR of both their leukemia/MPN. All 5 patients in CR/CP at pre-allo-SCT remain alive in remission, while 2/3 with persistent blood/marrow blasts relapsed and expired. We conclude that MPN-BP can be cured by allo-SCT in a significant percentage of patients, but that adequate leukemic clearance prior to allo-SCT offers an optimal outcome.