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AbstractBackgroundRespiratory syncytial virus (RSV) infection causes significant morbidity and mortality in allogeneic stem cell transplant (allo‐SCT) recipients. Although ribavirin and immunoglobulins are common components of therapy, the role of adjunct corticosteroids is not established.ObjectivesWe sought to evaluate corticosteroid utilization in the setting of post‐allo‐SCT RSV infection in our center and assess post‐transplant outcomes including pulmonary function decline.MethodsPatients with a history of RSV infection from 2008 to 2014 seen at our institution were identified. Treatment and outcome data were retrospectively collected. Forced expiratory volume at 1 s (FEV1) and carbon monoxide diffusion capacity (DLCO) were collected pre‐ and post‐RSV infection.ResultsDuring the observation period, RSV was isolated in 53 of 552 patients undergoing allo‐SCT (10%) and 45 had evaluable therapy data. RSV‐related mortality in this cohort was 4/45 (9%). Twenty‐one (47%) were on corticosteroids prior to RSV diagnosis, of whom 11 (24%) had a dose increase post symptom onset. Eight (18%) patients were started on corticosteroids at the time of RSV infection. Corticosteroid therapy at symptom onset was associated with a higher rate of upper respiratory infection (URTI) to lower respiratory infection (LRTI) progression risk ratio (RR) 2.49 (1.21–5.13; P = 0.016), hospital admission RR 2.05 (1.24–3.37; P = 0.005), or intensive care unit admission RR 2.91 (1.89–5.01; P = 0.002). No significant difference was seen with FEV1 and DLCO decline (P = 0.3 and 0.24, respectively) or mortality (P = 0.26).ConclusionAdjunct corticosteroid use in the setting of RSV infection did not improve RSV‐related outcomes including long‐term pulmonary function. Our results do not support the routine use of corticosteroids; however, this finding does need to be verified in a larger cohort of patients.

Objectives: Pulmonary complications are common following hematopoietic stem cell transplantation. Numerous idiopathic post-transplantation pulmonary syndromes have been described. Patients at the severe end of this spectrum may present with hypoxemic respiratory failure and pulmonary infiltrates, meeting criteria for acute respiratory distress syndrome. The incidence and outcomes of acute respiratory distress syndrome in this setting are poorly characterized. Design: Retrospective cohort study. Setting: Mayo Clinic, Rochester, MN. Patients: Patients undergoing autologous and allogeneic hematopoietic stem cell transplantation between January 1, 2005, and December 31, 2012. Interventions: None. Measurements and Main Results: Patients were screened for acute respiratory distress syndrome development within 1 year of hematopoietic stem cell transplantation. Acute respiratory distress syndrome adjudication was performed in accordance with the 2012 Berlin criteria. In total, 133 cases of acute respiratory distress syndrome developed in 2,635 patients undergoing hematopoietic stem cell transplantation (5.0%). Acute respiratory distress syndrome developed in 75 patients (15.6%) undergoing allogeneic hematopoietic stem cell transplantation and 58 patients (2.7%) undergoing autologous hematopoietic stem cell transplantation. Median time to acute respiratory distress syndrome development was 55.4 days (interquartile range, 15.1–139 d) in allogeneic hematopoietic stem cell transplantation and 14.2 days (interquartile range, 10.5–124 d) in autologous hematopoietic stem cell transplantation. Twenty-eight-day mortality was 46.6%. At 12 months following hematopoietic stem cell transplantation, 89 patients (66.9%) who developed acute respiratory distress syndrome had died. Only 7 of 133 acute respiratory distress syndrome cases met criteria for engraftment syndrome and 15 for diffuse alveolar hemorrhage. Conclusions: Acute respiratory distress syndrome is a frequent complication following hematopoietic stem cell transplantation, dramatically influencing patient-important outcomes. Most cases of acute respiratory distress syndrome following hematopoietic stem cell transplantation do not meet criteria for a more specific post-transplantation pulmonary syndrome. These findings highlight the need to better understand the risk factors underlying acute respiratory distress syndrome in this population, thereby facilitating the development of effective prevention strategies.

BACKGROUNDABO incompatibility is not a contraindication to hematopoietic cell transplantation (HCT), but it has been associated with additional risks including delayed engraftment, pure red cell aplasia (PRCA), and higher transfusion needs. Data on these events and on patient survival after reduced‐intensity conditioning (RIC) HCT are limited.STUDY DESIGN AND METHODSA total of 127 consecutive patients, 86 with acute myeloid leukemia and 41 with myelodysplastic syndromes, who underwent HLA‐matched peripheral blood RIC allogenic HCT between 2005 and 2014 were retrospectively analyzed.RESULTSEighty ABO‐compatible, 26 major/bidirectional, and 21 minor‐ABO‐mismatch HCT were identified. Compared to the ABO‐compatible group, major/bidirectional mismatches had increased red blood cell (RBC) transfusion requirement during the first 100 days (p = 0.009), delayed RBC and PLT engraftment (p = 0.0011 and p = 0.005, respectively), and higher incidence of grade II to IV acute graft‐versus‐host disease (aGVHD; p = 0.037). In multivariable analysis, major/bidirectional mismatches had significantly higher non‐relapse mortality (NRM) and inferior disease‐free survival (DFS) and overall survival (OS) compared with ABO‐compatible patients (p = 0.01, p = 0.04, and p = 0.035, respectively). Minor ABO mismatch had no impact on survival (p = 0.99). Four (15%) of 26 major/bidirectional mismatches developed PRCA. There was a significant association between fludarabine plus busulfan conditioning and PRCA (p = 0.0046).CONCLUSIONMajor/bidirectional ABO mismatch is associated with higher NRM and shortened DFS and OS in the setting of RIC HCT. Increased transfusion need, delayed RBC and platelet engraftment, PRCA, and increased severity of aGVHD are additional complications contributing to the morbidity.

AbstractBackgroundVoriconazole is a commonly used antifungal medication in allogeneic hematopoietic stem cell transplantation (allo‐HSCT) patients. In solid organ transplantation, voriconazole use has been associated with the development of cutaneous squamous cell carcinoma (SCC). We sought to determine if voriconazole use was associated with SCC in patients undergoing allo‐HSCT.MethodsWe retrospectively reviewed consecutive adult patients who underwent allo‐HSCT at Mayo Clinic from January 2007 through July 2012. Multivariable Cox models were created to assess the relationship of SCC with two time‐dependent voriconazole exposure variables: (i) history of voriconazole exposure (yes/no), and (ii) cumulative days of voriconazole use.ResultsIn our cohort of 381 allo‐HSCT patients, SCC developed in 26 of 312 patients exposed to voriconazole (25 post‐voriconazole) and in 1 of 69 patients who received alternative antifungal agent(s). Cumulative incidence of SCC was estimated to be 19% at 5 years post allo‐transplant. Cumulative days of voriconazole use was found to be a risk factor for SCC, and this relationship persisted in a multivariable model using previously identified risk factors as covariates (hazard ratio 1.859 for each 180 days of use, P < 0.001).ConclusionThis is the first study, to our knowledge, to identify cumulative days of voriconazole use as a risk factor for SCC development following allo‐HSCT, and may help guide appropriate antifungal use in this patient population.

SummaryMomelotinib (a JAK1 and JAK2 inhibitor) induces both anaemia and spleen responses in myelofibrosis (MF). Momelotinib treatment‐emergent peripheral neuropathy (TE‐PN) was documented in 44 (44%) of 100 MF patients treated at our institution; median time of TE‐PN onset was 32 weeks and duration 11 months. Improvement after drug dose reduction or discontinuation was documented in only two patients. TE‐PN was significantly associated with treatment response (P = 0·02) and longer survival (P = 0·048) but significance was lost during multivariate analysis that included treatment duration. TE‐PN did not correlate with initial or maximum momelotinib dose or previous treatment with JAK inhibitor or thalidomide.

Transplant‐associated thrombotic microangiopathy (TA‐TMA) is a rare clinical syndrome associated with significant mortality. Although the use of plasma exchange (PE) in TA‐TMA continues to be explored, evidence for its efficacy is debated. We performed a single institution, retrospective study to evaluate the efficacy of PE in treating TA‐TMA patients. Special attention was given to efficacy in relation to the timing of presentation with TA‐TMA since transplant. Thirty‐three patients diagnosed with TA‐TMA and treated with PE between January 1999 and December 2010 were included in the study. Clinical improvement was seen in eight patients (24%); four patients achieved complete resolution while the remaining four achieved partial resolution. All‐cause day‐30 and day‐100 mortality was 33 and 55%, respectively. There was a trend toward a better outcome (complete/partial) for those presenting ≥ 100 days after transplantation (42%) vs. < 100 days after transplantation (14%; P‐value = 0.15). Similarly, those presenting at ≥ 100 days had better, but not significantly, 30‐day and 100‐day all‐cause mortality rates (17 and 33%, respectively) than those presenting at < 100 days (43 and 67%, respectively) (P‐value = 0.25 and 0.08, for 30‐ and 100‐day all‐cause mortality, respectively). This is the first study looking at the efficacy of PE while considering the time of presentation since transplantation and is one of the largest single institution series of TA‐TMA. The overall efficacy of PE is poor; however, patients who present with TA‐TMA ≥100 days after transplant may have better outcome and lower mortality. J. Clin. Apheresis 30:147–153, 2015. © 2014 Wiley Periodicals, Inc.

PurposeAdvanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown.Patients and MethodsIn a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non–mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC).ResultsResponses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response.ConclusionAlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial.

AbstractBackgroundAutologous stem cell transplant (ASCT) is the current standard of care for most patients with multiple myeloma (MM) who are transplant eligible, yet the timing ofASCTis disputed due to a similar overall (OS) and progression‐free survival with an earlyASCT(eASCT) or a delayedASCT(dASCT) approach.ObjectiveWe developed a decision analytic model to perform cost‐effectiveness analysis of the two commonly used treatment strategies forMM.MethodsData on disease progression and treatment effectiveness came from 2001 to 2008 cohort treated at the Mayo Clinic and from published studies. Cost analysis was performed from a third‐party payer perspective.ResultsThe Consumer Price Index adjusted 2012 costs ofeASCTanddASCTwere $249 236 and $262 610, respectively.eASCTcohort had a benefit of 1.96 quality‐adjusted life years (QALYs), 0.23 QALYs more thandASCT, implying thateASCTis preferred (dominant) overdASCT. The most critical variables in one‐way sensitivity analysis were treatment‐related mortality and OS associated witheASCTstrategy.ConclusionsWe conclude thateASCTcould potentially be a relatively cost‐effective treatment option for appropriate patients with MM, and these results would help patients, providers, and payers in decision making for timing of ASCT.