Leyla Shune

Fatal GvHD induced by PD-1 inhibitor pembrolizumab in a patient with Hodgkin's lymphoma.

290. 10 Armand P, Nagler A, Weller EA, Devine SM, Avigan DE, Chen Y-B et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international Phase ii trial. J Clin Oncol 2013; 31: 4199–4206. 11 Villasboas JC, Ansell SM, Witzig TE. Targeting the PD-1 pathway in patients with relapsed classic Hodgkin lymphoma following allogeneic stem cell transplant is safe and effective. Oncotarget (e-pub ahead of print 3 February 2016; doi:10.18632/oncotarget.7177). 12 Mori S, Ahmed W, Patel RD, Dohrer AL. Steroid refractory acute liver GvHD in a Hodgkins patient after allogeneic stem transplant cell transplantation following treatment with anti PD-1 antibody, nivolumab, for relapsed disease. Biol Blood Marrow Transplant 22: S392–S393. ABVD (6 cycles) ICE x 2 Autologous transplant: BEAM Brentuximab Allogeneic transplant: Flu/TBI Brentuximab Pembrolizumab Death from GVHD Diagnosis 7 Months relapse 10 Months 27 Months progression 31 Months 43 Months relapse 58 Months relapse 60 Months death Figure 1. Clinical course of the patient. Letter to the Editor

Monosomal karyotype at the time of diagnosis or transplantation predicts outcomes of allogeneic hematopoietic cell transplantation in myelodysplastic syndrome.

Various cytogenetic risk scoring systems may determine prognosis for patients with myelodysplastic syndromes (MDS). We evaluated 4 different risk scoring systems in predicting outcome after allogeneic hematopoietic cell transplantation (alloHCT). We classified 124 patients with MDS using the International Prognostic Scoring System (IPSS), the revised International Prognostic Scoring System (R-IPSS), Armands transplantation-specific cytogenetic grouping, and monosomal karyotype (MK) both at the time of diagnosis and at alloHCT. After adjusting for other important factors, MK at diagnosis (compared with no MK) was associated with poor 3-year disease-free survival (DFS) (27% [95% confidence interval, 12% to 42%] versus 39% [95% confidence interval, 28% to 50%], P = .02) and overall survival (OS) (29% [95% confidence interval, 14% to 44%] versus 47% [95% confidence interval, 36% to 59%], P = .02). OS but not DFS was affected by MK at alloHCT. MK frequency was uncommon in low-score R-IPPS and IPSS. Although IPSS and R-IPSS discriminated good/very good groups from poor/very poor groups, patients with intermediate-risk scores had the worst outcomes and, therefore, these scores did not show a progressive linear discriminating trend. Cytogenetic risk score change between diagnosis and alloHCT was uncommon and did not influence OS. MK cytogenetics in MDS are associated with poor survival, suggesting the need for alternative or intensified approaches to their treatment.

Erythropoietin modulation is associated with improved homing and engraftment after umbilical cord blood transplantation

Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34+ cells. A significant population of UCB CD34+ HSPC expresses cell surface EPOR. Exposure of UCB CD34+ HSPC to EPO inhibits their migration and enhances erythroid differentiation. This migratory inhibitory effect was reversed by depleting EPOR expression on HSPC. Moreover, systemic reduction in EPO levels by hyperbaric oxygen (HBO) used in a preclinical mouse model and in a pilot clinical trial promoted homing of transplanted UCB CD34+ HSPC to BM. Such a systemic reduction of EPO in the host enhanced myeloid differentiation and improved BM homing of UCB CD34+ cells, an effect that was overcome with exogenous EPO administration. Of clinical relevance, HBO therapy before human UCB transplantation was well-tolerated and resulted in transient reduction in EPO with encouraging engraftment rates and kinetics. Our studies indicate that systemic reduction of EPO levels in the host or blocking EPO-EPOR signaling may be an effective strategy to improve BM homing and engraftment after allogeneic UCB transplantation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT02099266).

Novel disease burden assessment predicts allogeneic transplantation outcomes in myelodysplastic syndrome

Among patients with myelodysplastic syndrome (MDS) undergoing hematopoietic cell transplantation (HCT), the impact of residual pretransplant cytogenetically abnormal cells on outcomes remains uncertain. We analyzed HCT outcomes by time of transplant disease variables, including (1) blast percentage, (2) percentage of cytogenetically abnormal cells and (3) Revised International Prognostic Scoring System (R-IPSS) cytogenetic classification. We included 82 MDS patients (median age 51 years (range 18–71)) transplanted between 1995 and 2013 with abnormal diagnostic cytogenetics. Patients with higher percentages of cytogenetically abnormal cells experienced inferior 5-year survival (37–76% abnormal cells: relative risk (RR) 2.9; 95% confidence interval (CI) 1.2–7.2; P=0.02; and 77–100% abnormal cells: RR 5.6; 95% CI 1.9–19.6; P<0.01). Patients with >10% blasts also had inferior 5-year survival (RR 2.9; 95% CI 1.1–7.2; P=0.02) versus patients with ⩽2% blasts. Even among patients with ⩽2% blasts, patients with 77–100% cytogenetically abnormal cells had poor survival (RR 4.4; 95% CI 1.1–18.3; P=0.04). Increased non-relapse mortality (NRM) was observed with both increasing blast percentages (P<0.01) and cytogenetically abnormal cells at transplant (P=0.01) in multivariate analysis. We observed no impact of disease burden characteristics on relapse outcomes due to high 1-year NRM. In conclusion, both blast percentage and percentage of cytogenetically abnormal cells reflect MDS disease burden and predict post-HCT outcomes.

Outcomes of VDPACE with Immunomodulator Agent as a Salvage Therapy for Relapsed/Refractory Multiple Myeloma

27 mg/dL. Ibrutinib was held due to its common side effect, bleeding. The patient was referred to Urology to rule out bladder cancer with the concern of a prior history of cyclophosphamide treatment. Cystoscopy demonstrated mildly elevated bladder neck, otherwise normal for any acute pathology. Overall, it was thought that the benign bleeding could be from the prostatic urethra irritation and patient was started on tamsulosin. In the follow-up appointment patient had a bleeding for 20 minutes from the venipuncture site. The further evaluation for bleeding showed that patient had decreased vWF Ag (33%), vWF Activity (13%) and aVWFD was diagnosed. Meanwhile, patient’s IgM was 778 mg/dL. Ibrutinib was resumed considering that the IgM increased. In the next follow-up, patient’s bleeding symptoms were resolved and did not recur, his IgM decreased to 32 mg/dL and vWF Ag (229%), vWF Activity (204%) dramatically increased. Discussion: This case describes the challenge of diagnosing the etiology of bleeding in WM and highlights the importance of systematic approach. The incidence of hyperviscosity syndrome and related bleeding has decreased with early diagnosis of WM. Ibrutinib, a Bruton tyrosine kinase inhibitor used in WM has a main side effect of bleeding related to abnormalities in platelet aggregation. aVWFD can be associated with various mechanisms affecting vWF: autoantibodies, decreased synthesis, adsorption on cancer cells, damage. IgM autoantibodies against vWF in WM and associated aVWF disease is rarely observed. Although there are several mechanisms for bleeding in WM, the systematic approach to evaluate will be key to elucidate the underlying diverse mechanisms.

Utility of Routine Surveillance Imaging for Hodgkin Disease following Autologous Transplant: Experiences from a Single Institution

Background: Surveillance scans performed after autologous stem cell transplant (auto-HCT) for patients with Hodgkin disease (HD) have no proven survival benefit. Methods: We studied survival differences among patients with HD after auto-HCT whose recurrences were detected on clinical history and exam, versus those detected on routine surveillance scan. Results: Among the 98 patients with HD that underwent auto-HCT from 2000 to 2014 at our institution, 30 relapsed, of which 21 were detected radiologically and 9 clinically. There were no statistically significant differences in patient characteristics between the 2 groups. The median time to progression was 118 days for the clinical cohort and 284 days for the radiological cohort (p = 0.05). Median overall survival (OS) was 728 days for the clinical cohort, and was not reached for the radiological cohort (p = 0.02). Discussion: In our review, most patients with HD after auto-HCT were diagnosed radiologically. Patients whose relapse was diagnosed clinically were likely to be detected earlier and have a shorter OS. Patients with aggressive disease may be detected when clinically relevant, regardless of scanning. Routine scanning may not be necessary in the majority of patients with HD following auto-HCT.

Evaluation of cytomegalovirus reactivation and tolerability in seropositive umbilical cord transplant patients after implementation of an intensive prevention strategy

OBJECTIVE/BACKGROUNDnCytomegalovirus (CMV) causes significant morbidity and mortality in CMV seropositive patients undergoing umbilical cord blood transplants (UCBT). Our study aimed to describe the incidence of CMV reactivation and burden of disease, as well as the tolerability of an intensive prevention strategy as compared to historical prevention.nnnMETHODSnThis was a retrospective chart review of 33 CMV seropositive patients that underwent UCBT. The intensive prevention strategy in UCBT consisted of ganciclovir 5mg/kg/d intravenously or valganciclovir 900mg by mouth daily initiated at the beginning of the conditioning regimen until Day -2. Then from Day -1 to Day +100, patients received valacyclovir 2g by mouth three times daily, and from Day +101 to Day +365, acyclovir 800mg by mouth twice daily. Historical standard prevention was acyclovir 800mg by mouth twice daily initiated at the beginning of the conditioning regimen until Day +365.nnnRESULTSnThirty-three patients were included from 2008 to 2014. There were no differences in the adverse effects experienced between the two regimens (p=.4). CMV reactivation occurred significantly later with intensive prevention (p=.003). The median CMV viral titer at reactivation was lower in the intensive versus the historic prevention (1,800copies/mL and 2,700copies/mL, respectively), but was not significantly different. CMV disease occurred significantly less often in the intensive group (p=.039).nnnCONCLUSIONnThe results from this study indicate that the intensive prevention strategy was well tolerated, significantly delayed CMV reactivation, and patients had less CMV disease.