Induction Therapy Followed by Allogeneic Stem Cell Transplant for MPN Blast Phase: Outcomes From Mayo Clinic in Arizona

Abstract Abstract 1749 BACKGROUND: We have previously reported that transformation of a myeloproliferative neoplasm (MPN) to acute leukemia or blast phase (MPN-BP) is accompanied by a median survival of 2.6 months (range 0–24.2 months) (Mesa et. al. Blood 2005) despite treatment. Allogeneic stem cell transplantation (ASCT) offers a potential for cure. We reviewed 13 patients with MPN – BP who were candidates for ASCT, and 8 of those patients received ASCT after induction chemotherapy. METHODS: Retrospective analysis of individuals who had a clear antecedent myeloproliferative neoplasm (essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF) (either primary (PMF) or post ET/PV)), transformed to MPN-BP, and were candidates for ASCT. Clinical characteristics at each phase of illness, therapy at each phase of illness, and outcome of ASCT were assessed. RESULTS: Patients (MPN details): Thirteen patients (8 male, 5 female, median age at diagnosis of MPN 42 years in those who underwent ASCT and 64 years in those who did not receive ASCT (combined median 53 years, range 26–70)) were identified who met the inclusion criteria, of whom 2 had ET, 4 PV, 2 Post-ET MF, 1 Post-PV MF and 4 PMF. Jak2-V617F mutation was present in 7 of 8 patients tested. Treatments used during the MPN phase included hydroxyurea in 9 (+ busulfan in 1 and + anagrelide in 1), and thalidomide/prednisone in 2 (two patients received no treatment prior to MPN-BP). Patients (MPN-BP details): Transformation of an MPN to blast phase (from diagnosis of MPN) occurred after a median of 11 years in those who underwent ASCT and 8 years in non-ASCT (range 3 months to 30 years). At the time of MPN-BP diagnosis, 9 patients had an abnormal karyotype, 3 with complex karyotypes, 3 with trisomy 8 (sole abnormality), 1 with del(7q), 1 with del(13q). Leukemic induction consisted of standard anthracycline/cytarabine combination therapy (+/− etoposide), except for one patient received a study medication voreloxin. One patient who did not receive ASCT had remission after induction, but later expired from relapse, two expired soon after leukemic transformation, and two were too ill to receive induction. In the ASCT group (N=8), 5 patients achieved complete remission (CR) of their leukemia/return to MPN chronic phase (one of the five patients required a second induction to achieve CR), while 3 patients were considered primary induction failures due to persistence of > 5% blasts in the blood (2) or marrow (1) at the time of pre-transplant response assessment. The median time from diagnosis of MPN-BP to ASCT was 128 days. ASCT Details and Outcomes: Patients (median age of 55 years at time of ASCT; range 44–73) underwent ASCT (all HLA identical, 3 matched unrelated donors, 5 matched sibling donors) with either reduced intensity conditioning (n=6) or fully myeloablative conditioning (n=2). After a median follow-up of 488 days (range 127 – 1206), 6 of 8 patients are alive and free of disease. MPN-BP recurred in two patients at day 69 and 77 post-transplant; both patients eventually died of progressive leukemia, one after a second transplant. Acute GVHD occurred in 3 patients (1 grade III, 2 grade II), and chronic GVHD in 4 (2 mild, 2 moderate). All five patients who achieved CR (marrow and PB blasts < 5%) after induction therapy remain in continuous CR, while 2 of the 3 patients with evidence of persistent leukemia relapsed and died of MPN-BP. No patient died of transplant-related causes and all patients engrafted promptly. CONCLUSION: Rapid induction followed by ASCT can offer a curative path for individuals with MPN-BP. Although limited by small numbers, our data suggest that leukemic clearance (marrow blast percentage < 5%) prior to ASCT is associated with improved outcome. Disclosures: Mesa: Incyte: Research Funding; Lilly: Research Funding; SBio: Research Funding; Astra Zeneca: Research Funding; NS Pharma: Research Funding; Celgene: Research Funding.

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Allogeneic Stem Cell Transplantation for Accelerated/Blastic Phase Philadelphia-Chromosome Negative MPN

Blood ◽

10.1182/blood.v120.21.4532.4532 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4532-4532

Author(s):

Anjum Bashir Khan ◽

Donal McLornan ◽

Yogesh Jethava ◽

Kavita Raj ◽

Victoria T Potter ◽

...

Keyword(s):

Stem Cell ◽

Median Time ◽

Peripheral Blood ◽

Research Funding ◽

Myeloproliferative Neoplasm ◽

Chronic Phase ◽

Haematopoietic Stem Cell ◽

Cell Transplant ◽

Blastic Phase

Abstract Abstract 4532 Myeloproliferative Neoplasm (MPN)-Leukaemic Transformation (LT) uniformly carries a dismal prognosis. Effective therapy for such patients are currently lacking with no established evidence base to guide Allogeneic Haematopoietic Stem Cell Transplant (AHSCT) regimen. We report the outcome of a cohort of patients undergoing AHSCT at our 2 institutions over a 6-year period (2006–2012). 24 patients underwent AHSCT following diagnosis of MPN transformed to an accelerated phase (5–9% blasts on bone marrow (BM), n=9 & 10–19% BM blasts, n=2) or blastic phase (>20% blasts on peripheral blood or BM, n=13). Disease subtypes were: Polcythaemia Vera (PV, n=4), Essential Thrombocythaemia (ET, n=6), Primary Myelofibrosis (PMF, n=8), Myelodysplastic/Myeloproliferative neoplasm-Unclassified (MDS/MPN-U, n=6). Median age at diagnosis was 50 years (range 29–67) and median time to transformation was 50 months (range 0–271). Cytogenetics were abnormal at transformation in 11 patients (46%), with 6 (25%) demonstrating abnormalities of chromosomes 5, 7 or complex karyotype, and 5 displaying trisomy 8, whilst 1 had isolated chromosome 17p deletion. 13 patients harboured the JAK2V617F mutation. Patients received a median of 3 (range, 1–5) lines of therapy for chronic and acute phase prior to AHSCT, of which 20 patients received intensive AML-type induction therapy. Disease status at time of AHSCT was complete remission (CR) in 13 cases, partial response (PR) in 7, and 4 patients had persisting AML. Conditioning regimes were Reduced Intensity with T-depletion (Alemtuzumab or Anti-Thymocyte globulin) in 23/24 cases (Fludarabine/Busulfan-based n=12, FLAMSA (Fludarabine, Ara-C and Amsacrine, followed by TBI/Cyclophosphamide or Busulfan) n=9, Fludarabine Cyclophosphamide TBI haploidentical protocol n=1, Fludarabine/Melphalan n=1). Median CD34 dose was 6.48 × 10∧6 cells/kg (range 1.17 {BMH} −10.71). Stem cell source was Peripheral Blood in all but one case, from unrelated (n=17) or related (n=7) donors. Median time to both neutrophil and platelet engraftment was 13 days (range 9–25 and 7–68 respectively); 2 patients including the haploidentical transplant had Primary Graft Failure (8%). The incidence of severe (grade 3&4) acute GVHD was 3/24 (12.5%) and 10 patients developed NIH-defined chronic GVHD (8 moderate, 1 severe). Day 100 Non-relapse mortality was 12.5%. Patients underwent sequential chimerism monitoring. Median OS for the entire cohort was only 10 months with a median progression free survival (PFS) of only 6.5 months. 5 patients received therapeutic Donor Lymphocyte Infusion (tDLI) for relapse at a median dose of 1×10∧6 CD3+/kg. 2 patients received DLI alone for chronic phase relapse, of whom 1 achieved remission. 3 patients received chemotherapy + DLI and 1 achieved 2ndCR. At last follow-up, 11/24 patients were alive with median surviving patient follow-up of 25 months. The percentage of BM blasts at progression from chronic phase had a highly significant impact upon outcome post AHSCT, median OS 23 vs. 10 months for 5–9% BM blasts compared to 310% BM blasts (p=0.011) & PFS 11 vs 6 months respectively (p=0.033, Fig 1). This effect was replicated when considering disease response immediately prior to AHSCT, with a median OS of 28 months for those in CR, compared to 10 months for those with excess blasts (p=0.017) and median PFS 11 vs 6 months, p=0.019 (Fig 2). Disease duration, subtype, Jak2 status and age at allograft did not significantly affect survival. Of note for the 3 surviving patients with follow-up over 6 months, all received FLAMSA-RIC conditioning (n=9). 5 patients who received FLAMSA TBI; 2 died of treatment-related complications, and 2 with residual disease at time of AHSCT relapsed early. Of 4 patients who have received a hybrid FLAMSA-Busulfan regimen, 2 remain alive in CR and 2 achieved a relapse free period of 12 months. Interestingly, PFS for FLAMSA-Bu patients appears significantly improved compared to conventional RIC regimens (median PFS 12 vs. 6 months, p=0.035) on univariate analysis, although conclusions are limited by cohort size. Further work into optimising transplantation regimens for accelerated and blastic phase MPN is warranted. Early use of FLAMSA-Busulfan hybrid protocol, before transformation to overt blastic phase, in conjunction with early weaning of immunosuppressive therapy and prophylactic DLI may improve the proportion of long-term survivors. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures: Harrison: Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding; YM Bioscience: Consultancy, Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau.

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A Second Autologous Stem Cell Transplant (ASCT2) Induces Superior Durability Of Response (DuR) Following Bortezomib-Containing Re-Induction Therapy For Relapsed Multiple Myeloma (MM): Final Results From The BSBMT/Ukmf Myeloma X (Intensive) Trial

Blood ◽

10.1182/blood.v122.21.765.765 ◽

2013 ◽

Vol 122 (21) ◽

pp. 765-765 ◽

Cited By ~ 1

Author(s):

Gordon Cook ◽

Cathy D. Williams ◽

David A Cairns ◽

Marie Fletcher ◽

J. D. Cavenagh ◽

...

Keyword(s):

Quality Of Life ◽

Stem Cells ◽

Stem Cell ◽

Induction Therapy ◽

Salvage Therapy ◽

Research Funding ◽

Phase Iii ◽

Cell Transplant ◽

End Point

Abstract Introduction Although ASCT in MM is standard consolidative therapy in first line treatment definitive evidence for its use in salvage therapy is lacking. The principal aim of this multi-centre phase III randomised controlled trial was to evaluate the durability of response (DuR) of a second ASCT compared with a less intensive alkylating agent consolidation, after a bortezomib-containing re-induction strategy. Patients and Methods Eligible patients with MM relapsing after a prior ASCT were enrolled. All patients were re-induced with PAD therapy (Bortezomib 1.3mg/m2 iv D1, 4, 8 & 11; Doxorubicin 9mg/m2/day iv D1-4; Dexamethasone 40mg/day PO D1-4: additionally D8-11 & D15-18 on cycle 1 only) delivered in 4-6 21-day cycles before 1:1 randomization to either a second ASCT (Melphalan 200mg/m2 iv; ASCT2 supported by either stored stem cells or remobilized stem cells) or low dose consolidation with weekly cyclophosphamide 400mg/m2 PO for 12 weeks (C-weekly). Response assessment (by IMWG criteria) was analyzed after re-induction and 100 days post-randomization and time-to-disease progression (TTP) determined. Patients were stratified by β2microglobulin (β2M) at trial entry and response to re-induction and analyzed according to cytogenetic abnormalities by iFISH (unfavorable: t(4,14), t(14,16) and del17p). The primary endpoint was Time-to-progression (TTP) with secondary endpoints of OS, overall response rate (to PAD and randomized intervention), feasibility of stem cell mobilization in salvage therapy, safety & quality of life. Results The Data and Safety Monitoring Board (DSMB) recommended randomization closure and early result release owing to the primary end-point having been met. 297 patients were entered into the study and 174 randomized from April 2008 to November 2012: ASCT2 n = 89, C-weekly n = 85. Median age was 61 (range 38 -75) with 73.6% of patients relapsing more than 24 months from first ASCT. ORR to re-induction therapy was 79.4%% with 16.0% sCR/CR rate. Post-randomization, sCR/CR was significantly higher in ASCT2 (39.3%, 95% CI 29.1, 50.3) than C-weekly (22.4%, 95% CI 14.0, 32.7) cohorts with more patients upgrading response to sCR/CR in the ASCT2 (n = 22) than C-weekly (n = 7) cohorts. At the time of analysis, 125 of 174 patients have progressed, 57 in the ASCT2 (64%) and 68 in the C-weekly (80%) cohorts. Median TTP was 19 months (95% CI 16, 25) for ASCT2 compared with 11 months (95% CI 9, 12) for C-weekly (HR 0.36 95% CI 0.25, 0.53; Cox regression analysis p<0.0001). Response to re-induction therapy (HR 2.90, 95% CI 1.45, 5.63; p = 0.0017) and DuR from ASCT1 (HR 3.49, 95% CI 1.07, 11.45; p = 0.039) had a significant impact on TTP. The median β2M level at registration was 2.7mg/L (range 1.3- 11.6) with a trend to improved TTP in patients undergoing ASCT2 when a β2M was <3.5 vs ≥ 3.5mg/L (HR 0.48, 95%CI 0.21, 1.08; p = 0.077). The presence of unfavorable iFISH did not impact on TTP in the C-weekly cohort but had a significant impact on TTP in the ASCT2 cohort (interaction HR 0.08, 95% CI 0.02, 0.41; p = 0.0024). TTP in patients with unfavorable iFISH was similar in the ASCT2 and C-weekly cohorts. Overall, 15 (17%) in the ASCT2 and 17 (20%) in the C-weekly arms have died with PD accounting for 8 and 9 deaths, respectively. Currently, there is no impact of the post-randomization intervention on OS (HR 0.62, 95%CI 0.3, 1.3; p = 0.193), though interpretation is limited by the current short follow-up and patients in the C-weekly cohort who received a second ASCT after reaching the primary end-point. Conclusion The final analysis demonstrates a clear advantage in terms of durability of response when a second high dose Melphalan-conditioned ASCT consolidates re-induction therapy with a bortezomib-containing regimen in myeloma patients at first relapse. The impact on overall survival and quality of life remains to be clarified. Disclosures: Cook: Janssen: Honoraria, Research Funding, Speakers Bureau. Williams:Janssen: Honoraria, Speakers Bureau. Snowden:Janssen: Honoraria, Research Funding, Speakers Bureau. Cavet:Janssen: Research Funding.

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Myeloma Canada Research Network (MCRN)-001 Trial Utilizing Bortezomib (btz)-Based Induction, Enhanced Conditioning with IV Busulfan + Melphalan (BuMel) and Lenalidomide (len) Maintenance in Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplant (ASCT): A National Canadian Study Evaluating Achievement of Minimal Residual Disease (MRD) Negativity and Involved Serum HevyliteTMÂ chain (HLC) Normalization

Blood ◽

10.1182/blood.v126.23.1982.1982 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1982-1982

Author(s):

Donna Reece ◽

Giovanni Piza Rodriguez ◽

Mariela Pantoja ◽

Darrell White ◽

Christopher P. Venner ◽

...

Keyword(s):

Flow Cytometry ◽

Stem Cell ◽

Missing Data ◽

Maintenance Therapy ◽

Induction Therapy ◽

Research Funding ◽

Residual Disease ◽

Research Network ◽

Multiparameter Flow Cytometry ◽

Cell Transplant

Abstract As therapy for MM improves, methods more sensitive than conventional serum/urine electrophoresis/immunofixation are required to optimally evaluate response. Our phase 2 multi-center clinical trial, conducted in 10 Canadian centers, utilized serial bone marrow aspirate (BMA) samples for MRD analysis by 8-color multiparameter flow cytometry (MFC), along with serum Hevylite assay of the involved heavy light chains (HLC), to assess responses after ASCT and during maintenance therapy. After btz-based induction therapy (usually CyBorD), pts without progression received enhanced conditioning with BuMel (IV busulfan 3.2 mg/kg days -5 to -3 or days -6 to -4 + melphalan 140 mg/m2 day -2 or day -3) followed by ASCT on day 0. On day 100 post-ASCT, lenalidomide (len) 10 mg/day was commenced, escalated to 15 mg/day after 3 cycles if appropriate, and continued until progression. BMA and serum samples were shipped centrally for MRD and Hevylite analysis before induction therapy, before ASCT, on day 100 post-ASCT, every 3 mos for the 1st year and every 6 mos until progression. From 03/2013 - 07/2015, 122 newly diagnosed pts provided BMA samples for MRD analysis. To date, 70 pts (target 78), have completed induction therapy and undergone ASCT; 8 others provided pre-induction samples and are expected to be enrolled. 44 of the 122 (36%) who provided BMA samples did not proceed to BuMel due to: poor samples-4 pts (3.2%); MM not confirmed-3 pts (2.5%); prior therapy-1 pt (0.8%); death during induction-1 pt (0.8%); consent withdrawal/opted for standard conditioning-19 pts (15.6%); and no ASCT-16 pts (13.1%; 8 were unfit, 4 had comorbidities, 2 progressed, 1 failed mobilization and 1 received tandem ASCT for high-risk MM). Median follow-up is 17.4 mos (range: 6.3-25.6). Median age is 57 (34-69); 64% are male. Median serum β2-microglobulin level is 3.07 mg/L (1.5-20) and albumin 37 g/L (2.8-48.1); 31 pts have ISS stage I; 18 stage II; 15 stage III MM and 6 have missing data. Ig subtype includes IgGκ in 30 (43%), IgGλ in 14 (20%), IgAκ in 8 (12%), IgAλ in 9 (13%), κ in 5 (7%); λ in 1 (1%) and missing data in 3 pts (4%). Post-ASCT, 14 SAEs have occurred: Grade 3 atrial fibrillation (2), acute kidney injury (3), increased creatinine (1), upper respiratory infection (2), febrile neutropenia (2), bacteremia (1), hypoxia (1) and lung infection (1) and Grade 4 sepsis (1). There have been no ASCT-related deaths; 4 pts have progressed. The best conventional Ig response post-induction in the 66 pts with available data is CR in 5 (7.6%), VGPR in 25 (38%), PR in 31 (47%), MR in 4 (6%) and SD in 1 (1.5%). The Ig response at day 100 in the 60 evaluable pts includes CR in 10 (17%), VGPR in 30 (50%), PR in 18 (30%), MR in 1 (1.5%) and SD in 1 (1.5%). MRD negativity improved from 18/67 (27%) after induction to 22/60 (37%) at day 100 (Table 1). Among evaluable pts, 83.3% of those after induction and 68.2% of those at day 100 who were MRD-negative had normal involved HLC ratios, while 42.6% and 51.5% of those who were MRD-positive, respectively, had normal ratios. Table 1. Response Rates by Conventional Serum/Urine Parameters and Marrow Flow Cytometry for MRD MRD Negativity by Conventional Ig Response # Evaluable Normal Hevylite ratio (# normal /evaluable) (%) # MRD Negative (%) CR VGPR PR MR SD Missing Total MRD(-) Total MRD(-) Total MRD(-) Total MRD(-) Total MRD(-) Total MRD(-) After Induction 67 15/18 (83.3%) 18 (27%) 5 4 25 9 31 5 4 0 1 0 1 0 Day 100 Post-ASCT 60 15/22 (68.2%) 22 (37%) 10 4 30 16 18 2 1 0 1 0 0 0 Conclusions: 1) IV BuMel conditioning + ASCT was well-tolerated with few SAEs and no ASCT-related deaths; 2) at day 100 post-ASCT, 97% had achieved ≥ PR (≥ VGPR in 67% and CR in 17%); 3) MRD negativity rates improved from 27% to 37% after ASCT; 3) conventional Ig and MRD responses were often discordant as only 40% of CR pts were MRD-negative at day 100; 4) the majority of MRD-negative patients also had normalization of their involved HLC ratios; 5) further F/U is required to determine the rate of achievement of MRD negativity during maintenance therapy; relationships between conventional Ig response, MRD status and involved HLC ratio; and long-term outcomes with this approach. Disclosures Reece: Janssen: Consultancy, Honoraria, Research Funding; Osuka: Honoraria, Research Funding; Merck: Research Funding; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Millennium: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Off Label Use: Lenalidomide maintenance after autologous stem cell transplantation. White:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Venner:Amgen: Honoraria; Celgene: Honoraria, Research Funding; J&J: Honoraria, Research Funding. Sebag:Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria. Song:Celgene: Honoraria; Otsuka: Honoraria; Janssen: Honoraria. Tay:Celgene: Honoraria; Janssen: Honoraria. Kukreti:Janssen: Honoraria; Celgene: Honoraria. Trudel:Amgen: Honoraria, Speakers Bureau; Oncoethix: Research Funding; BMS: Honoraria; Novartis: Honoraria; Celgene: Equity Ownership, Honoraria, Speakers Bureau; Trillium Therapeutics Inc.: Research Funding. Anca:Janssen: Honoraria; Celgene: Honoraria. Tiedemann:Janssen: Honoraria; Celgene: Honoraria. Chen:Celgene: Honoraria, Research Funding; Millennium: Research Funding; Janssen: Honoraria.

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Haplo-Cord Transplantation Vs Unrelated Donor Stem Cell Transplantation in Patients with AML/MDS Older Than 50

Blood ◽

10.1182/blood.v124.21.1235.1235 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1235-1235 ◽

Cited By ~ 3

Author(s):

Joanna Rhodes ◽

Koen van Besien ◽

Hongtao Liu ◽

Usama Gergis ◽

Stephanie B. Tsai ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Research Funding ◽

Chronic Gvhd ◽

Unrelated Donor ◽

Cell Transplant ◽

Advisory Committees ◽

Post Transplant

Abstract Haplo-cord Transplantation Vs Unrelated Donor Stem Cell Transplantation In Patients with AML/MDS older than 50 Between 2007 and 2013, 109 patients with AML/MDS who were 50 years and older and had no HLA- matched related donor underwent allogeneic hematopoietic stem cell transplant. 64 had an HLA identical unrelated donor and received fludarabine/melphalan/alemtuzumab conditioning and post transplant tacrolimus for graft vs host disease (GVHD) prophylaxis. 45 underwent haplo-cord (HC) SCT with fludarabine/melphalan/ thymoglobulin; post-transplant tacrolimus and MMF. We compared patient characteristics and transplant outcomes between both groups. (Table 1) Age distribution and ASBMT risk category were similar. There were more patient's with AML in the HC group. (P=0.01) Time to neutrophil recovery, treatment related mortality (TRM), relapse rate, progression free survival (PFS) and overall survival (OS) were nearly identical between the two groups. Time to platelet recovery was on average 5 days longer after HC (p=0.05) The incidences of acute and chronic GVHD were very low in both groups, in part due to the use of in-vivo T cell depletion. HC transplant with reduced intensity conditioning is a curative treatment for older patients with AML/MDS who lack HLA identical unrelated donors. Despite inclusion of many patients with high risk features, nearly two thirds were estimated to be alive one year after transplant and very few had chronic GVHD. Haplo-cord grafts are more readily available, a potential advantage over MUD grafts in situations where transplant is needed urgently. TableMatched Unrelated DonorHaplo Cord PN6445Age (range)62 (50-73)62 (50-74)AML/MDS45/2041/5 0.01ASBMTLow/Int /High21/6/3015/10/200.7KPS 9090Time to ANC >50010110.1Time to Plt >2018230.05PFS@ 1 Y (95% CI)46 (34-58)41 (26-56)0.6OS@ 1 Y (95% CI)57 (44-70)64 (49-79)0.8Cum Inc TRM @100 d (95% CI)9 (2-16)9 (0-18)0.2Cum Inc TRM @ 1 Y(95% CI)25 (14-36)29 (15-44)0.2Cum Inc Relapse @ 1Y (95% CI)30 (18-42)26 (12-40)0.5Cum Inc AGVHD @ 100 D (95% CI)25 (14-36)29 (13-43)0.7Cum Inc CGVHD @ 1 Y (95% CI)6 (0-12)7 (0-15)0.9 Disclosures van Besien: Miltenyi: Research Funding. Mark:Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Artz:Miltenyi: Research Funding.

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Therapy Related MDS/AML In Multiple Myeloma Patients In The Era Of Novel Agents

Blood ◽

10.1182/blood.v122.21.3117.3117 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3117-3117

Author(s):

Morie A Gertz ◽

Suzanne R Hayman ◽

David Dingli ◽

Angela Dispenzieri ◽

Prashant Kapoor ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Research Funding ◽

Stem Cell Transplant ◽

The United States ◽

Lymphocytic Leukemia ◽

Novel Agents ◽

Cell Transplant ◽

Trisomy 8 ◽

To Receive

Introduction With the introduction of novel agents, survival in multiple myeloma has successively increased in the past decade. This improved survival increases the risk for late complications. Patients continue to receive melphalan therapy as a standard induction for those over the age of 65. Lenalidomide is considered a standard component of induction therapy in the United States for patients who are transplant candidates. Stem cell transplantation remains the standard of care for patients eligible to receive it. As a consequence of exposure to lenalidomide, stem cell transplant, and melphalan, the risk of late myelodysplasia and acute leukemia remains significant. We reviewed the Mayo Clinic experience with therapy-induced myelodysplasia beginning with the advent of novel agents. Patients and Methods All patients that carry the diagnosis of multiple myeloma between January 1, 2000, and September 1, 2011, were included. Patients with a synchronous diagnosis of a myeloproliferative or a myelodysplastic disorder or those who developed the myelodysplastic disorder within 15 months of first chemotherapy exposure were excluded. The date of diagnosis for the purpose of this abstract was based on first exposure to chemotherapy and not first detection of a monoclonal protein or smoldering multiple myeloma. All patients had to have morphologic verification in the bone marrow of dysplastic change consistent with therapy-related myelodysplasia. Results Of 3111 patients who had a myeloma diagnosis and first treatment after January 1, 2000, through September 1, 2011, 22 patients were identified to fulfill the criteria of myelodysplasia. There were 13 men and 9 women with a median age of 67 (46 to 82). At the time of this report, 17 have died. Prior to the development of myelodysplasia, exposure to an alkylating agent, lenalidomide, or an auto stem cell transplant was seen in 13, 15, and 10, respectively. Only one patient had been exposed to lenalidomide alone. Eighteen patients were classified as myelodysplasia. Four had acute non-lymphocytic leukemia. Metaphase cytogenetics was available in 19 and only one was normal. Twelve were hypodiploid. Trisomy 8 or abnormalities of chromosome 5 and 7 were present in 13. Seven patients received a hypomethylating agent with no clear evidence of response in any. Four patients had an allotransplant to manage the MDS/AML and only one survives 487 days after a matched-related donor allogeneic transplant. The median time from initial therapy of multiple myeloma to recognition of MDS or AML was 50.9 months (range: 15.2-146.5 months) fig 1. The median overall survival of the 22 patients is 6.5 months. Fig 2 Six of the 22 had active myeloma at the diagnosis of MDS/AML. Conclusion Myelodysplasia during the era of novel agents is a devastating complication of therapy with a very short survival and low response rate. As a time-dependent complication, the overall risk cannot be accurately estimated but has occurred in <1% of our patient population to date. Hypomethylating agents were ineffective in the seven that received it. One of four allotransplant patients remains alive. Ongoing surveillance for MDS/AML in this population is warranted and more effective therapies are needed. Disclosures: Kumar: Onyx: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

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Impact Of Vitamin D Level Pre and Post Allogeneic Hematopoietic Stem Cell Transplant

Blood ◽

10.1182/blood.v122.21.4616.4616 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4616-4616 ◽

Cited By ~ 1

Author(s):

Kristen Beebe ◽

Jane Olsen ◽

Yu-hui Chang ◽

Mary Burkhart ◽

Lori DeCook ◽

...

Keyword(s):

Vitamin D ◽

Stem Cell ◽

Bacterial Infection ◽

Hematopoietic Stem Cell ◽

Research Funding ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Chronic Gvhd ◽

Cell Transplant ◽

Hematopoietic Stem

Introduction Allogeneic hematopoietic stem cell transplant (HCT) patients are at risk for having a low Vitamin D (VD) level. VD level has been correlated with cancer incidence, pulmonary disease and infection. VD also has immunomodulatory properties and reports suggest that a low VD level increases the incidence of chronic GVHD and may impact mortality in HCT. HCT morbidity and mortality is attributed to infection, organ system toxicity, GVHD and recurrent disease. Identifying a correctable factor that would reduce the occurrence or severity of these complications would be beneficial. It is possible that VD may have significant effect on outcome after HCT due to its described properties. Normal VD level may infer better outcome for HCT patients by improving response in or preventing infection, protecting organ function, decreasing risk of relapse and/or decrease incidence or severity of GVHD. We hypothesize that there is a relationship between VD level and morbidity and mortality after HCT. We therefore studied VD levels pre- and post-HCT to determine if there was an impact of VD level on these outcomes. Patients and Methods Two hundred and fifty patients underwent myeloblative or non-myeloablative HCT between 3/12/2009 and 10/29/2012 at our institution. Baseline demographic data, disease characteristics, transplant variables and outcomes data were obtained from the transplant database. These data were supplemented by retrospective chart review for VD levels prior to transplant, at day 100 and 1 year post-HCT. Data were collected through day 100 for occurrence of infection and admissions to the ICU. Categories for VD level included normal (≥30 ng/ml) or abnormal (<30 ng/ml). Patient characteristics were compared using the Chi-square test or Wilcoxon rank sum test. The logrank test was used to compare the survival curves between groups, and the Cox proportional hazard model was used to measure the association between outcomes (mortality, relapse, acute or chronic GVHD) and VD level. Results Of the 250 patients undergoing HCT VD level was performed on 180 (72%) patients pre-HCT, 149 (60%) patients at day 100 post-HCT and 81 (32%) patients at 1 year post-HCT. The rate of acute or chronic GVHD was not significantly associated with VD level pre or post-HCT. Overall infection risk was not significant pre or post-HCT but when sorted by type of infection bacterial infection (p=0.01), radiologic evidence of pulmonary nodules/consolidation (p=0.03), and ICU admissions (p=0.0313) within the first 100 days post-transplant were significantly increased in patients who had a low VD level at day 100 post -HCT. Pre-HCT and 1 year post-HCT VD level did not impact mortality or relapse but there was a significant increase in one year mortality (p=0.02, HR = 5.99) and relapse (p = 0.03, HR=9.47) in patients who had a low VD level at day 100 post-HCT. Discussion This study shows that VD may play a significant role in bacterial infection, pulmonary infection, ICU admission, mortality and relapse after HCT. Those patients with a low VD level at day 100 post-HCT had significantly worse outcomes for relapse and mortality. Those patients with a low VD level at day 100 post-HCT had a higher incidence of lung infection, bacterial infection and admission to the ICU. In contrast to previous studies, we found no correlation between VD level and incidence of acute or chronic GVHD. This study is one of the largest reported and the first to our knowledge that reports decreased risk of certain types of infection (bacterial and lung), mortality and relapse in those with an adequate VD level receiving HCT. It is possible that supplementation of VD to keep levels ≥30 would reduce these complications of HCT. Future prospective study of VD is warranted. Finding a low cost and easy to administer therapy (such as VD replacement) that would reduce morbidity, mortality and relapse in the HCT population is needed. Disclosures: Reeder: Celgene: Research Funding; Novartis: Research Funding; Millenium: Research Funding.

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Treatment and Management of Chronic Myelogenous Leukemia in Patients Cared for in a Large HMO

Blood ◽

10.1182/blood.v124.21.1310.1310 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1310-1310

Author(s):

Reina Haque ◽

Jiaxiao Shi ◽

Joanie Chung ◽

Chantal C Avila ◽

Lei Chen ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Health Plan ◽

Research Funding ◽

Stem Cell Transplant ◽

Chronic Phase ◽

Cell Transplant ◽

First Line ◽

Median Length

Abstract Introduction CML management has rapidly changed in the last decade. Data are critically needed to characterize disease treatment, management, and drug use (particularly TKIs, tyrosine kinase inhibitors) to ultimately inform how to improve outcomes in patients with CML. Our objective was to describe practice trends in a large community based health plan serving over 3.2 million members in southern California, Kaiser Permanente (KPSC). Methods Patients were identified from the health plan’s NCI-SEER affiliated cancer registry. The cohort consisted of 257 CML adult patients (18+ years, chronic phase, no prior cancer history) all diagnosed between January 2001 and December 2012 and followed through December 31, 2013. We collected data from electronic health records and chart reviews including demographics, TKI use and adherence, healthcare utilization and clinical outcomes. Medication possession ratio (MPR) was used to measure adherence, calculated as the number of days supplied divided by the number of days between first and last dispense date of any TKI. We classified patients into MPR>90% (indicates good adherence) and MPR<90%. Discontinuation was ascertained from providers’ notes in the medical charts. Results Of the 257 patients with newly diagnosed chronic phase CML, 111 were female (43%). About 58% (n=148) were non-Hispanic Whites, and 23% (n=59) were Hispanic. About half (48%, n=124) had one or more existing comorbidities. Over 90% of the cohort initiated TKI therapy within 3 months of diagnosis, and mean MPR was 88% (s.d. 18%). About two-thirds of the patients (63%, N=157) had an MPR>90% for TKI use. Virtually all patients (96%) started on imatinib. Of the 59 cases diagnosed 2010-2012, only 14 used dasatinib or nilotinib as first line therapy. Half of the cohort (n=107) discontinued first line treatment (mainly imatinib). Reasons for discontinuation included general adverse effects (e.g., skin rash, muscle cramps), cardiovascular, lung or abdominal effects (n=41); incomplete cytogenetic or molecular response (n=38); drug non-response, provider recommended, not compliant (n=21); or BMT/stem cell transplant (n=7). The cohort was followed a maximum of 13 years (mean 5.1 years, s.d. 3.1 years). The total number of hospitalizations was 351 among patients diagnosed 2001-2006; 113 diagnosed 2007-2009; and 71 diagnosed 2010-2012. The median length of each hospitalization was 10 days (s.d. 30.6) during the follow-up years. Among imatinib users, the median number of overall outpatient visits per year varied from 20 visits/year for patients diagnosed 2001-2006 to 11 visits/year for patients diagnosed 2010-2012. Overall, 18 patients underwent bone marrow and/or stem cell transplant (all diagnosed 2001-2006). We examined progression and overall survival in patients diagnosed in 2001-2006 and exposed to imatinib. The rate of progression to accelerated phase or blast crisis was lower in patients with MPR>90% (10.0/1,000 person-years) than with MPR<90% (14.2/1,000 person-years). Similarly, patients with MPR>90% had a lower mortality rate (25.9/1,000 person-years) than patients with MPR<90% (39.2/1,000 person-years). Kaplan Meier curves for overall survival also demonstrate better survival, but not significantly (log rank P=0.35), among those with MPR>90%. Figure 1 Figure 1. Discussion Most patients initiated TKI therapy within 90 days of diagnosis in this health plan. Our results show median length of each hospitalization was 10 days across all follow-up time. Despite having full pharmacy coverage, the percent of subjects with MPR>90% was moderate (64%). Our results also suggest that subjects with MPR>90% for TKIs had lower progression rates and greater overall survival, but the results were not significant, and need to be confirmed in a larger study. Next steps include examining the frequency of cytogenetic and molecular testing and how this might impact outcomes, and factors associated with lower TKI medication possession ratios. Disclosures Haque: Novartis: Research Funding. Shi:Novartis: Research Funding. Chung:Novartis: Research Funding. Avila:Novartis: Research Funding. Chen:Novartis: stock options Other. Schottinger:Novartis: Research Funding.

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Survival Outcomes Following Allogeneic Stem Cell Transplantation for Inherited Bone Marrow Failure and Myeloid Germline Predisposition Syndromes

Blood ◽

10.1182/blood-2019-121742 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3300-3300

Author(s):

Kalyan Nadiminti ◽

Abhishek A Mangaonkar ◽

Kimberly J. Langer ◽

Shakila P Khan ◽

Vilmarie Rodriguez ◽

...

Keyword(s):

Stem Cell ◽

Fanconi Anemia ◽

Research Funding ◽

Bone Marrow Failure ◽

Chronic Gvhd ◽

Cell Cancer ◽

Survival Outcomes ◽

Unrelated Donor ◽

Cell Transplant ◽

Short Telomere

Introduction: Allogeneic stem cell transplant (HCT) is the only potential curative option for patients with inherited marrow failure (iBMF) and myeloid germline predisposition syndromes (GPD). HCT outcomes are influenced by inherent disease specific-nuances such as alkylating agent and radio-sensitivity, immune deregulation, and higher risks for graft failure and GVHD; factors contributing to transplant related mortality (TRM) and morbidity. We carried out this retrospective study to assess survival outcomes and long term complications (LTC) in patients with IBMF and GPD that underwent HCT. Patients and methods: We queried our institutional database and identified patients with iBMF and GPD as defined by the 2016 WHO classification. These included Fanconi anemia (FA), short telomere syndromes (STS), Diamond-Blackfan anemia (DBA), GATA2 and RUNX1 haploinsufficiency, congenital amegakaryocytic thrombocytopenia (CAMT), deficiency of adenosine deaminase 2 (DADA2), among others. Patients with acquired causes of BMF were excluded. Statistical analyses were performed using SAS (JMP v14.1). Results: Twenty eight patients, median age 10 years (1 month-63 years), 46% males, were included in the study (table 1). Fanconi anemia Seven (25%) patients with FA underwent HCT, 5 (71%) without myeloid transformation and 2 after transformation to MDS/AML. Five (71%) patients received a RIC, 4 (57%) prior to transformation. At a median follow up (FU) of 126 m, the median OS was 194 m (95% CI 34m; NR) and 10 year survival was 64%. Grade 1 aGVHD was seen in four (57%) and 3 (42%) developed mild cGVHD, while 1 developed a donor derived AML (sibling not tested for FA). LTC included second primary malignancy (SPM) - squamous cell cancer (SCC) of skin and muscle invasive bladder cancer (MIBC) in 1(14%) and SCC of head/neck and anogenital region in 3 patients (43%), psychosocial complications (PS) in 6(85%), premature ovarian failure (POF) in 3(43%), and avascular necrosis (AVN) in 4(57%) patients. Short Telomere Syndromes (STS) Seven patients with STS underwent HCT, 2 (28%) after transformation to MDS. Five (71%) received RIC, including both the transformed patients. At a median FU of 67m, median OS was NR (95% CI 2m; NR) and 5 year survival was 47%. One (14%) patient developed grade 2 aGVHD and mild cGVHD of skin. Three (43%) developed SPM - skin cancers in 2 and MIBC in 1. PS was noted in 1(15%), and AVN in 3(43%). Three (43%) patients had concomitant mild IPF/restrictive lung disease. GATA2 haploinsufficiency : Seven patients with GATA2 haploinsufficiency underwent HCT; 2(28.5%) after transformation to MDS and 3(43%) to AML, of which 2(40%) received MAC. At a median FU of 57m, median OS was NR (95% CI 7m; NR) and 5 year survival was 71%. Three (50%) developed grade 2 aGVHD of skin and GI tract and 2(33%) developed mild cGVHD. LTC include PTLD, AVN and POF in 1 patient each. Ribosomopathies : One patient (13y) with DBA underwent RIC HCT and developed grade 2 aGVHD, secondary iron overload, and died at 10 months due to severe fungal infection. Others : Identical twins with CAMT underwent HCT (at 4y and 5y) from the same unrelated donor and at last FU (74m and 87m, respectively) remain 100% donor without GVHD. Two children with primary immunodeficiency and marrow failure underwent HCT (at 2y and 7y), one after transformation to MDS. The non-transformed patient is currently alive (120m), while the patient with transformation died 1month after HCT from disseminated cytomegalovirus infection. One patient with germline RUNX1 deletion developed CMML and underwent a RIC HCT and is alive at a FU of 4 months, with no GVHD. One patient with DADA2 (n=1) underwent RIC HCT without LTC. Due to the smaller cohort size, we compared OS in transformed and non-transformed patients for the IBMF and GATA2 patients only (n=24, 9 with transformation) (figure1). At a median FU of 74m, the median OS of transformed vs non-transformed patients was 108m(95% CI 1;108m) and 163m(95% CI 67m; NR), respectively (p=0.033). Conclusions: Our study demonstrates that HCT remains an important intervention for IBMF and GPD, with the maximum impact being gained prior to transformation. While only mild chronic GVHD was noted (37%), inherent syndromic issues resulted in a high rate of SPM (FA/STS) and organ failure (STS- IPF). Notably, one FA patient who received an MRD HCT developed donor derived AML, underlining the importance of genetic screening in asymptomatic related individuals. Disclosures Kenderian: Lentigen: Research Funding; Kite/Gilead: Research Funding; Morphosys: Research Funding; Humanigen: Other: Scientific advisory board , Patents & Royalties, Research Funding; Novartis: Patents & Royalties, Research Funding; Tolero: Research Funding. Patnaik:Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees.

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Combination of the Hypercvad Regimen with Dasatinib Is Effective in Patients with Relapsed Philadelphia Chromosome (Ph) Positive Acute Lymphoblastic Leukemia (ALL) and Lymphoid Blast Phase Chronic Myeloid Leukemia (CML-LB).

Blood ◽

10.1182/blood.v114.22.2043.2043 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2043-2043 ◽

Cited By ~ 3

Author(s):

Farhad Ravandi ◽

Hagop M. Kantarjian ◽

Jorge Cortes ◽

Deborah A. Thomas ◽

Stefan Faderl ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Research Funding ◽

Stem Cell Transplant ◽

High Dose ◽

Cell Transplant ◽

Allogeneic Stem Cell Transplant ◽

Blast Phase ◽

Median Response ◽

Platelet Recovery

Abstract Abstract 2043 Poster Board II-20 Background: The dual Src and Abl inhibitor dasatinib is ∼325 times more potent than imatinib in vitro against the kinase activity of BCR-ABL and has significant clinical activity in patients with imatinib-resistant lymphoid blast phase CML (CML-LB) and Ph+ ALL. Prognosis of patients with relapsed Ph+ ALL and CML-LB is poor with few effective options other than allogeneic stem cell transplant. Aim: To investigate the feasibility of and response to a combination of chemotherapy and dasatinib to patients with relapsed Ph+ ALL or CML-LB. Methods: Patients with relapsed Ph+ ALL or CML-LB received dasatinib 50 mg po bid (or 100 mg daily) for the first 14 days of each of 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate. Patients in CR continued to receive maintenance with dasatinib 50 mg po bid (or 100 mg daily) and vincristine and prednisone monthly for 2 years followed by dasatinib indefinitely. Result: To date, 23 patients with relapsed Ph+ ALL (n=14) or CML-LB (n=9) have received a median of 3 cycles of this regimen (range 1-8 cycles). Median age was 49 years (range 21-69); 10 (43%) patients were older than 50 years. Median WBC at start of treatment was 9.6 × 109/L (range, 0.4 – 295.5 × 109/L). Median bone marrow blast percentage was 80% (range 0-98%). Six patients had CNS involvement. Pre-treatment ABL mutations included: 1 patient with F317L, 1 M351T, 1 T315I, 1 Y253F, 1 Y253H, and 1 with Y253H, F359V, and E459K). Median number of previous therapies was 1 (range, 1-4); these include hyperCVAD plus imatinib (n=8), other combination chemotherapy regimens (n=8), monotherapy with tyrosine kinase inhibitors other than dasatinib (n=7), investigational agents (n=2) and allogeneic stem cell transplantation (n=2). All patients were evaluable for response. 15 patients (65%) achieved CR, 6 patients (26%) achieved CR with incomplete platelets recovery (CRp), 1 patient (4%) did not have day 21 bone marrow to assess response, and 1 patient (4%) died during induction. Nineteen of 21 (90%) patients have achieved a major cytogenetic response after 1 cycle of therapy, complete in 17, 1 (5%) had insufficient metaphases, and 1 (5%) had no response (still had 95% Ph+ metaphases after 1 cycle). Overall, so far 15 (65%) patients had achieved a major molecular response, complete in 10. Median time to neutrophil and platelet recovery for the first cycle was 18 and 22 days, and for subsequent cycles, 18 and 26 days, respectively. Nine patients have relapsed after median response duration of 26 weeks (range, 8-49); six of them had acquired ABL kinase domain mutations (1 T315I and E450G; 3 T315I; 1 F317L, and 1 G303fs). Three patients proceeded to an allogeneic transplantation and one previously transplanted patient received a donor lymphocyte infusion. Grade 3 and 4 adverse events included bleeding (GI, GU, and subdural hematomas)(9), pleural effusions (5), pericardial effusions (2), as well as infections, diarrhea, hypophosphatemia, hypocalcemia, elevated transaminases, and hyperbilirubinemia. With a median follow up of 13 months (range, 5-52 months), 10 patients are alive; 8 are in CR/CRp. Seven patients died after disease relapse, 1 died post transplant, 4 died in CR/CRp from infections, and 1 died of unknown causes. The median survival was 39 weeks (range, 2 to 226 weeks) with 42% of patients alive at 1 year. Conclusion: The combination of the hyperCVAD regimen with dasatinib is feasible and effective in patients with relapsed Ph-positive ALL and CML-LB and can provide a bridge to an allogeneic stem cell transplant. Disclosures: Ravandi: Bristol Myers Squibb: Honoraria, Research Funding. Kantarjian:Bristol Myers Squibb: Research Funding. Cortes:Bristol Myers Squibb: Research Funding. O'Brien:Bristol Myers Squibb: Research Funding.

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Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplant (HSCT) for Myeloma (MM) - Chronic Graft Versus Host Disease (GVHD) is Associated with Lower Risk of Relapse and Superior Progression Free Survival (PFS) - A CIBMTR Analysis.

Blood ◽

10.1182/blood.v114.22.53.53 ◽

2009 ◽

Vol 114 (22) ◽

pp. 53-53

Author(s):

Parameswaran N Hari ◽

A. John Barrett ◽

Smriti Shrestha ◽

Gisela Tunes da Silva ◽

Mei-Jie Zhang ◽

...

Keyword(s):

Stem Cell ◽

Lower Risk ◽

Research Funding ◽

Chronic Gvhd ◽

Cell Transplant ◽

Allogeneic Hsct ◽

Matched Sibling ◽

The Impact ◽

Reduced Intensity ◽

Risk Of Relapse

Abstract Abstract 53 Prior studies have demonstrated a graft-versus-malignancy effect following allogeneic HSCT that is variably linked to acute or chronic GVHD. Although a graft vs. Myeloma (MM) effect has been shown after myeloablative allogeneic HSCT, a higher treatment related mortality (TRM) risk leads to inferior survival compared with autologous HSCT. Non-myeloablative (NMA) and reduced intensity conditioning (RIC) approaches are used to reduce the risk of TRM while preserving the graft vs. MM effect. The clinical benefit of lower intensity conditioning regimens is thus especially dependent on the impact of acute or chronic GVHD on graft vs. MM effect and TRM. We analyzed the outcomes of 177 matched sibling allogeneic HSCT recipients reported to the CIBMTR between 1997 and 2005 following NMA (n=120) or RIC (n=57) performed within 18 months of diagnosis. Median age was 50 (range 24-69) years and 62% were Durie-Salmon Stage III. Tandem autologous followed by allogeneic HSCT (autologous+ allogeneic) recipients (n=105) were more likely to receive NMA conditioning vs. recipients of an upfront allogeneic HSCT (n=72). Majority (98%) received peripheral blood stem cell grafts. Outcomes at a median follow-up of 36 (3 - 98) months are summarized in table 1. In order to assess the impact of GVHD on outcomes, Cox proportional hazards regression models were built with GVHD as the main effect treating it as a time dependent covariate (Table 2). Other covariates in the multivariate models included age, sex, performance status, IgG vs. non IgG myeloma, disease status and chemosensitivity, prior lines of chemotherapy, donor-recipient sex match, NMA vs. RIC and year of transplant. AGVHD was associated with an increased risk of TRM. Tandem autologous + allogeneic HSCT was associated with reduced relapse risk (RR= 0.49, p=0.008). AGVHD had no impact on relapse/progression of MM while cGVHD was associated with a reduced risk of relapse (Figure. 1). The protective effect of cGVHD on relapse was significant in the non IgG MM subgroup. AGVHD had no impact on PFS whereas cGVHD was associated with superior PFS and lower risk of treatment failure. Later year of HSCT was also associated with superior PFS. Overall survival was not affected by cGVHD while recipients of tandem autologous + allogeneic HSCT had a higher mortality in the presence of aGVHD (RR=3.60, p= 0.01). After matched sibling allogeneic HSCT for MM, aGVHD is associated with a higher risk of TRM whereas cGVHD decreases the risk of relapse and improves PFS. The effect of cGVHD may vary with the type of MM with greater impact in non IgG MM. Further study to identify subtypes of MM susceptible to an immune mediated graft vs. MM effect is suggested. Disclosures: Lonial: Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.

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