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We evaluated 71 patients treated with allogeneic hematopoietic cell transplantation (allo-HCT) for multiple myeloma (MM). Forty-three patients (61%) received allo-HCT after the first line of therapy. Fifty-eight patients (82%) had chemosensitive disease at the time of allo-HCT. A HLA-matched related or unrelated donor was available for 68 patients (96%). Non-myeloablative or reduced-intensity conditioning regimen and peripheral blood hematopoietic cells as a graft source were used in most patients. The cumulative incidence of grade II–IV acute GVHD at day +100 and chronic GVHD at 5 years was 13% (95% CI 7–23%) and 35% (95% CI 24–46), respectively. Non-relapse mortality and relapse/progression incidence at 5 years were 12% (95% CI 5–23) and 65% (95% CI 49–76), respectively. With a median follow-up in survivors of 100 months (range 16–186), the 5-year PFS and OS were 39% (95% CI 27–52) and 60% (95% CI 55–77), respectively. On multivariate analysis: age >55 years was associated with both a reduced PFS (RR 2.11, 95% CI 1.15–3.87) and OS (RR 5.53, 95% CI 2.22–13.76); chemorefractory disease at allo-HCT was associated with both reduced PFS (RR 3.09, 95% CI 1.37–7.00) and OS (RR 3.19, 95% CI 1.23–8.22). At relapse, 24 patients (56%) received bortezomib, 28 (65%) lenalidomide, 11 (26%) pomalidomide, 16 (37%) donor lymphocytes infusion as part of salvage therapy after allo-HCT relapse. Median PFS from time of salvage treatment was 7 months (range 0–113 months) for bortezomib-based therapy, 14 months (range 0–79 months) for lenalidomide and 10 months (range 1–28) for pomalidomide. Allo-HCT is a feasible and effective strategy in selected patients with MM and could be an effective platform for subsequent therapies.

Immunomodulatory drugs (IMiDs) may favor autoimmune disease (AD) occurrence. We conducted a retrospective study to evaluate AD occurrence among IMiD-treated patients with myeloma. Patients were grouped into three classes depending on the type of IMiD engaged. The first group included patients treated with thalidomide (Thal) (n = 474), the second group with lenalidomide (Len) (n = 140) and patients in the third group were first treated with Thal followed by Len (Thal-Len) (n = 94). Absolute risk of AD was 0.4% for patients treated with Thal, 4.3% for Len and 1.1% for Thal-Len. ADs manifested prevalently as autoimmune cytopenias (55%), although we observed one vasculitis, one optic neuritis, one Graves' disease and one polymyositis. ADs occurred preferentially in the first months of IMiD treatment. A previous autologous transplant was shown to be a significant risk factor. All ADs were managed with IMiD discontinuation and steroids, resolving in a few weeks, except for Graves' disease and polymyositis.

von Willebrand disease (VWD) is the most common inherited bleeding disorder and is caused by quantitative or qualitative defects of von Willebrand factor (VWF). VWF, synthesized by endothelium and megakaryocytes (MK), circulates in plasma and is present in subendothelium and platelets. Circulating endothelial cells (CEC) and progenitor endothelial cells (EPC) have been recently proposed as markers of peripheral and bone marrow-derived angiogenesis. To evaluate the association of CEC/EPC with known inherited defects of cellular and circulating VWF, we have measured the number of CEC/EPC together with cytokines involved in angiogenesis in different VWD types. A group of 74 patients was composed by the following VWD types: VWD1 (n = 22), VWD2A (n = 9), VWD2B (n = 19), VWD2M (n = 17), and VWD3 (n = 7). Healthy individuals (n = 20) were used as controls. CEC (CD146+, CD31+, and CD45−) and EPC (CD34+, CD133+, and CD45−) were evaluated by flow cytometry. Circulating serum levels of VEGF, E-selectin, P-selectin, EPO, and TPO were determined by ELISA. CEC, VEGF, E-selectin, and EPO were higher and EPC lower in VWD patients than in controls (P < 0.01). Among the five groups of VWD patients and controls, a significant difference was found for CEC (one-way ANOVA: P = 0.005), EPC (P = 0.001), E-Selectin (P < 0.0001), EPO (P = 0.021), and TPO (P = 0.004): the latter was high in VWD3 patients. In VWD1, we found an inverse relationship between CEC and VWF:Ag levels (P = 0.048; R2 = 0.19). Based on these data, CEC are increased in VWD and are associated with the high levels of cytokines involved in angiogenesis (up-regulation). EPC are decreased, suggesting down-regulation of bone marrow-derived angiogenesis in VWD. Am. J. Hematol. 2011. © 2011 Wiley-Liss, Inc.

e282 survival (OS) and progression-free survival (PFS) were 69% (95% CI:6-55%) and 35% (95% CI:6-22%), respectively (Figure 1). On multivariate analysis, chemorefractory disease at alloHCT was associated with an inferior PFS (Hazard risk [HR] 5.75 [95% CI:2.32-14.23]), inferior OS (HR 5.19 [95% CI:2.05-13.14]), higher toxicity related mortality (TRM, HR 6.60 [95% CI: 1.1139.02]) and higher RI/POD (HR 4.04 [95% CI: 1.07-15.21]). Being younger than 55 years emerged as a protective factor for both PFS (HR0.29 [95%CI:0.14-0.60]) and OS (HR 0.29[0.01-0.10]). Chronic GVHD conveyed a higher TRM (HR 1.15 [95%CI:1.021.30]) but not a reduced RI/POD. Conclusion: Our retrospective data show that RIC alloHCT is a safe and effective therapeutic option in MM patients, allowing long survival outcomes even in heavily pretreated patients. Figure 1 OS (A) and PFS (B) of the whole study population 15th International Myeloma Workshop, September 23-26, 2015 PO-349 Durable Remission and Survival in Relapsed/Refractory Multiple Myeloma After Allogeneic Hematopoietic Stem Cell Transplantation A.M. Cornelison, R.M. Saliba, S. Ahmed, Y. Nieto, Q. Bashir, N. Shah, S. Parmar, K. Patel, C. Hosing, U. Popat, E. Shpall, R. Champlin, M.H. Qazilbash Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HCT) in the setting of refractory multiple myeloma (MM) is still controversial. Although potentially curative in a subset of pts, 10-15% treatment related mortality (TRM) and chronic graft vs. host disease (cGVHD) preclude its universal use. In this study, we evaluated the role of allo-HCT for pts with relapsed MM. Methods: We identified 110 consecutive pts with relapsed MM who underwent allo-HCT at our institution between 2000 and 2014. The primary objective was to assess progression-free (PFS) and overall survival (OS). Results: Median age at allo-HCT was 54 (range, 32-71) years and median time from diagnosis to alloHCT was 35.7 (range, 8.6 to 228.8) months. Fifty-two (47%) and 49 (45%) pts had standard-risk (SR) and high-risk (HR) cytogenetics (CG) at the time of allo-HCT, respectively. Pts received a median of 5 (range, 1-9) prior chemotherapy regimens and 99 pts (90%) had at least 1 (range, 0-3) prior auto-HCTs. One hundred one(92%) pts received either a proteasome inhibitor (PI) or an immunomodulatory drug (IMiD) prior to allo-HCT, with 65 (59%) receiving both. Sixty eight (62%) received allo-HCT from a matched related, 34 (31%) from a matched unrelated, 5 (4%) from a cord blood, and 3 (3%) from a mismatched donor. Preparative regimen was fludarabine/melphalan-based in 88 (80%) and fludarabine/busulfan-based in 16 (15%) patients. Median time to neutrophil and platelet engraftment was 12 (range, 8-30) and 13 (range, 0-81) days, respectively. Ten pts died of non-relapse causes within 100 days (100-day TRM: 9%) and 20 (18%) within 1 year. Grade 1-4 acute GVHD was seen in 50 (45%) and cGVHD in 35 (32%) pts, respectively. Eighteen (16%) achieved a CR, 26 (23%) a VGPR and 38 (34%) achieved a PR, with an overall response rate of 73%. With a median follow up of 11.4 months (range 0.3 to 164) in all pts, and 32.7 months (range 3.6 to 164.3) in surviving pts, 1and 2-year PFS were 24% and 16%, respectively. Similarly, 1and 2-year OS were 52% and 32%, respectively. HR CG at allo-HCT and a response

Patients with relapsed and refractory Hodgkin lymphoma (HL) may experience long-term survival after allogeneic stem cell transplantation (alloSCT), but disease recurrence represents the main cause of treatment failure. Positron-emission tomography (PET)–positive patients after alloSCT have a dismal outcome. Serum thymus and activation-regulated chemokine (TARC) is produced by Reed-Sternberg cells and may be a marker of disease. Our study aimed at assessing whether TARC levels after alloSCT correlated with disease status and whether TARC monitoring could increase the ability to predict relapse. Twenty-four patients were evaluated in a prospective observational study. TARC serum level and PET were assessed before and after alloSCT during the follow-up (median, 30 months; range, 2 to 54). Before alloSCT, the median TARC level was 721 pg/mL (range, 209 to 1332) in PET-negative patients and 2542 pg/mL (range, 94 to 13,870) in PET-positive patients. After alloSCT, TARC was 620 pg/mL (range, 12 to 4333) in persistently PET-negative patients compared with 22,397 pg/mL (range, 602 to 106,578) in PET-positive patients (P < .0001). In 7 patients who relapsed after alloSCT, TARC level increased progressively even before PET became positive, with a median fold increase of 3.19 (range, 1.66 to 7.11) at relapse. The cut-off value of 1726 pg/mL had a sensitivity of 100% and a specificity of 71% for PET positivity. Patients with at least 1 TARC value above 1726 pg/mL during the first year after alloSCT had a worse progression-free survival (P = .031). In conclusion, TARC was correlated with disease status and its monitoring may be able to predict PET positivity after alloSCT, thus potentially allowing an early immune manipulation.