Impact of Allogeneic Stem Cell Transplantation as Salvage Therapy After T315I Mutation Detection in Chronic Myeloid Leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (ALL) Patients.

Abstract Abstract 645 Background: The development of a BCR-ABL T315I mutation is associated with a poor prognosis and limited therapeutic options. The impact of the mutation on the outcome of stem cell transplantation (SCT) is unknown. Aim: To describe the overall survival (OS) of CML patients in any phase and Ph+ ALL patients who received an allogeneic SCT after developing a T315I mutation after exposure to tyrosine kinase inhibitors (TKI). Methods: We conducted a retrospective, multi-center observational study of 222 CML and de novo Ph+ ALL patients who developed a T315I mutation between 1999 and 2008. Data from the medical records of 33 patients (15% of all patients in the registry) from 9 countries (USA, France, Italy, Germany, Denmark, Singapore, and the UK) who received an allogeneic SCT after T315I mutation detection were included in this study. Results: At the time of diagnosis, the median age was 39 years (range, 16-67); 70% were male; 26 patients were in CML CP, 1 in CML AP, 2 in CML BC, and 4 had Ph+ ALL. The median time between diagnosis and TKI treatment start was 3 months (range, 0-125), between diagnosis and T315I mutation detection was 28 months (range, 3-131), and between TKI treatment start and T315I mutation detection was 19 months (range, 2-64). Five (15%) patients had TKIs as frontline therapy. At the time of T315I detection, 10 patients were in CML CP, 7 in CML AP, 12 in CML BC, and 4 had Ph+ ALL. Hydroxyurea (alone or combined with other treatments) was the most common 1st line treatment (55%) after T315I mutation detection. The median time from T315I mutation detection to SCT was 3 months (range, 0.3-28). At the time of transplant, the median age was 42 years (range, 22-68); 8 patients were in CML CP, 7 in CML AP, 14 in CML BC and 4 had Ph+ ALL; 32 patients received 1 SCT and 1 received 2 SCTs after T315I mutation detection. The source of stem cells was peripheral blood (53%), bone marrow (35%), cord blood (6%), and unknown (6%). 82% were matched donor and 18% were unmatched. The median follow-up time from SCT was 7 months and 15 (55%) patients had died by their last follow-up. The OS of CML CP and CML AP patients was much better than CML BP and Ph+ ALL patients (Fig. 1; logrank, p=.050). The 1-yr OS rates (95% CI) from SCT were 69% (21-91%) for CML CP, 71% (26-92%) for CML AP, 16% (3-39%) for CML BC, and 33% (1-77%) for Ph+ ALL; and the 3-yr OS rates (range) was 69% (21-91%) for CML CP, 71% (26-92%) for CML AP, 0 for CML BC, and 0 for Ph+ ALL. Conclusion: These results suggest that the survival of patients harboring a T315I mutation and treated with allogeneic SCT is dependent on the disease phase at the time of SCT. SCT is the treatment of choice for these CML patients, particularly those in CP and AP.Fig. 1.Overall survival from Allogeneic SCTFig. 1. Overall survival from Allogeneic SCT Disclosures: No relevant conflicts of interest to declare.

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Outcome of Autologous Stem Cell Transplantation in Waldenström's Macroglobulinemia

Blood ◽

10.1182/blood-2018-99-116496 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2149-2149

Author(s):

Romil Patel ◽

Neeraj Y Saini ◽

Ankur Varma ◽

Omar Hasan ◽

Qaiser Bashir ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Research Funding ◽

Advisory Committees ◽

First Remission ◽

Relapsed Disease

Abstract Introduction: The role of autologous hematopoietic stem cell transplantation (auto-HCT) in the management of patients with Waldenström Macroglobulinemia (WM), a rare, indolent lymphoma, has not been established. We had previously published our experience with auto-HCT in a small cohort of WM patients1. Here, we present an updated analysis of auto-HCT with a larger cohort of WM patients. Methods and study population: The study cohort was comprised of 29 patients who underwent high-dose chemotherapy and auto-HCT at MD Anderson Cancer Center (MDACC). The Kaplan-Meier method was used to create survival curves. Overall survival (OS) was defined as the duration from date of transplant to death or last date of follow-up in living patients. Progression-free survival (PFS) was defined as the duration from date of transplant to either progressive disease or death, whichever occurred first. Results: Median age at auto-HCT was 60 (range, 43-75 years). Eight patients (28%) had concurrent light chain amyloidosis (AL). Of the five patients who had MYD88 testing completed, 3 were positive for the MYD88 mutation. Additionally, of these 3 patients, 2 were also positive for CXCR4 mutation. Patients received a median of 2 lines (range 1-6) of therapy prior to auto-HCT; 3(10%) patients had primary refractory disease, 8(28%) were in first remission, and 18 (62%) had relapsed disease. Median time from transplant to last follow-up for the surviving patients was 5.3 years. Preparative regimens received by the patients were: Melphalan (n=20), BEAM-R (n=2), Busulfan/Melphalan (n=1), Cyclophosphomaide/Etoposide/total body irradiation (n=1), Thiotepa/Busulfan/Cyclophosphamide (n=1), and Carmustine/Thiotepa (n=1). Three patients further went on to receive allogeneic transplant either after relapse from auto-HCT or due to disease transformation to aggressive lymphoma. Twenty-eight patients achieved engraftment with a median time to neutrophil engraftment of 11 days (range, 10-15 days). One patient suffered primary graft failure due to progression of disease and died 84 days after transplant. Non-relapse mortality was 3.4% at 1 year. All patients were eligible for response evaluation. The median OS from diagnosis was 12.2 years. Overall response rate was 96%: complete response (n=8, 27.6%), very good partial response (n=5, 17.3%), partial response (n=15, 51.7%), and progressive disease (n=1, 3.4%). PFS and OS at 5 years were 43.3% and 62.9%, respectively. Median PFS and OS from auto-HCT were 4.1 and 7.3 years (Fig. 1A). The median OS from auto-HCT in first remission + primary refractory and relapsed disease was 8.2 years and 4.1 years, respectively.16 patients were alive at the time of censoring while 13 patients had died. Causes of death include relapsed disease (n=6), secondary malignancy (n=2), infection (n=1), chronic graft-versus-host disease (n=1), and unknown (n=3). 8 patients (28%) were positive for concurrent AL amyloidosis. The sites of amyloid involvement were kidneys (n=2), lungs (n=1), bone marrow (n=1), heart(n=1), lymph nodes(n=1), gastrointestinal tract (n=1) and subcutaneous fat aspirate(n=5). The median overall survival for patients with amyloid involvement (n=8) was 12 years. On univariate analyses, the number of chemotherapy regimens prior to transplant (≤ 2 vs >2 lines) was the strongest predictor of overall survival (p=0.03, HR 0.3, CI: 0.09-0.9, log-rank) and PFS (p=0.001, HR 0.24, CI: 0.07-0.85, log-rank). The median PFS in patients with ≤ 2 lines and > 2 lines of therapy was 71 months versus 19 months, respectively (Fig. 1B). Conclusion: Auto-HCT is safe and feasible in selected patients with WM, with a high response rate and durable remission even in patients with relapsed or refractory disease. References: Krina Patel et.al. Autologous Stem Cell Transplantation in Waldenstrom's Macroglobulinemia. Blood 2012 120:4533; Disclosures Thomas: Celgene: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Array Pharma: Research Funding; Amgen Inc: Research Funding. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Orlowski:Takeda: Consultancy; Celgene: Consultancy; Spectrum Pharma: Research Funding; Janssen: Consultancy; Kite Pharma: Consultancy; Sanofi-Aventis: Consultancy; BioTheryX: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. Patel:Poseida Therapeutics, Inc.: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Celgene: Research Funding.

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Survival in Patients Who Underwent HLA-Haploidentical Stem Cell Transplantation in Two Centers in Colombia

Blood ◽

10.1182/blood-2020-141846 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 32-32

Author(s):

Lisbeth Ramirez ◽

Juan Manuel Herrera ◽

Angela María Peña ◽

Maria Luna-Gonzalez ◽

Claudia Marcela Chalela ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Retrospective Study ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Median Time ◽

Clinical Characteristics ◽

High Dose ◽

Post Transplantation ◽

Hematopoietic Stem

Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for several malignant and non-malignant hematological diseases. However, sometimes it is challenging to find human leukocyte antigen (HLA)-matched related or unrelated donors, especially in minority populations such as Hispanics. Transplantation of T cell replete HLA haploidentical graft (HaploHCT) followed by a high dose post-transplantation cyclophosphamide (PTCy) to eradicate alloreactive T cells is an option for populations with low donor availability. HaploHCT has emerged as an effective and safe strategy in this population (Luznik L et al. BBMT 2008), but data in Hispanics is scarce. Objective: The aim of our study was to describe the clinical characteristics and assess overall survival at 100 days, 1- and 3-years of patients who underwent haploHCT in two Colombian reference centers. Methods: An observational retrospective study was conducted at two tertiary referral centers in Colombia. Patients who underwent haploHCT at Clinica FOSCAL and Centro Medico Imbanaco between January 2013 and January 2020 were selected. Demographic and clinical characteristics where analyzed using descriptive statistics. The Kaplan-Meier method was used to assess overall survival (OS) rates and the log-rank test was used to compare survival rates between groups. All data were analyzed using R statistical software®. Results: Seventy-six patients were included. Mean age at transplantation was 34 years (range 18-60). Forty-two (57.89%) patients were female. Average body mass index was 19.86kg/m2. The majority of patients (57%) had a pre-transplantation ECOG performance status of 2. The most common indication for haploHCT was acute lymphoblastic leukemia (55.26%), followed by acute myeloid leukemia (23.64%). A sibling was the donor in 69.74% of the cases. Forty-seven (61.84%) patients were ABO-matched group. Peripheral blood stem cells were the graft source in 96% of the patients. The average number of infused CD34+ cells was 11.15 x 106/kg. Fludarabine-melphalan was the most commonly used conditioning regimen (57%), followed by fludarabine-busulfan-thiotepa (39%). Graft-versus-host disease (GVHD) prophylaxis consisted of PTCy (50 mg/kg/day) on days 3 and 4 after HCT and a calcineurin inhibitor plus mycophenolate mofetil from day 5 to day 35 post-HCT. Median time to neutrophil engraftment (neutrophils > 0,5x109/L) was 15 days (range 10-33), while platelet engraftment, defined as as the second day of unsupported platelet count of ≥20 × 109, occurred at a median time of 13 days (range 5-38) post-transplantation. On day 28 post-HSCT, 93.4% of the patients had achieved 100% chimerism. OS was 91% (95%CI 84-97.5) at 100 days, 81% (95%CI 72-90) at 1-year, and 77% (95%CI 68-88) at 3-years after HaploHCT. C onclusion: The results of our haploHCT retrospective study in a Hispanic population are comparable to several other cohorts that have reported similar outcomes of haploHCT compared to HLA-matched HCT. The OS rates reported in our study suggest that haploHCT is a viable option in patients without an HLA-matched related or unrelated donor available, especially in populations with lower rates of suitable donors. Acknowledgements: We deeply thank Gonzalo Gutiérrez García, M.D. for his leadership and guidance implementing the haploHCT program in Clinica FOSCAL. Disclosures Peña: Roche: Honoraria. Salazar:Janssen: Honoraria; Novartis: Honoraria. Sandoval-Sus:MorphoSys US: Consultancy; Janssen: Consultancy; Massive Bio: Consultancy; Celgene: Speakers Bureau. Sossa:Novo: Honoraria; Takeda: Honoraria; Astellas: Honoraria; Roche: Honoraria.

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Pre-transplant depression decreased overall survival of patients receiving allogeneic hematopoietic stem cell transplantation: a nationwide cohort study

Scientific Reports ◽

10.1038/s41598-020-71208-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Sheng-Min Wang ◽

Sung-Soo Park ◽

Si-Hyun Park ◽

Nak-Young Kim ◽

Dong Woo Kang ◽

...

Keyword(s):

Overall Survival ◽

Cohort Study ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem ◽

Depression Group

Abstract Studies investigating association of depression with overall survival (OS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) yielded conflicting results. A nationwide cohort study, which included all adult patients [n = 7,170; depression group, 13.3% (N = 956); non-depression group, 86.7% (N = 6,214)] who received allo-HSCT from 2002 to 2018 in South Korea, analyzed risk of pre-transplant depression in OS of allo-HSCT. Subjects were followed from the day they received allo-HSCT, to occurrence of death, or last follow-up day (December 31, 2018). Median age at allo-HSCT for depression and non-depression groups were 50 and 45 (p < 0.0001), respectively. Two groups also differed in rate of females (depression group, 55.8%; non-depression group, 43.8%; p < 0.0001) and leukemia (depression group, 61.4%; non-depression group, 49.7%; p < 0.0001). After a median follow-up of 29.1 months, 5-year OS rate was 63.1%. Cox proportional-hazard regression evaluated an adjusted risk of post-transplant mortality related to depression: OS decreased sequentially from no depression (adjusted hazard ratio [aHR] = 1) to pre-transplant depression only (aHR = 1.167, CI: 1.007–1.352, p = 0.04), and to having both depression and anxiety disorder (aHR = 1.202, CI: 1.038–1.393, p = 0.014) groups. Pre-transplant anxiety (anxiety only) did not have significant influence in OS. Additional medical and psychiatric care might be necessary in patients who experienced depression, especially with anxiety, before allo-HSCT.

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Immunotherapy with Rituximab after Peripheral Blood Stem Cell Transplantation for Multiple Myeloma.

Blood ◽

10.1182/blood.v104.11.5232.5232 ◽

2004 ◽

Vol 104 (11) ◽

pp. 5232-5232

Author(s):

Celso Mitsushi Massumoto ◽

Edilson Pinheiro Junior ◽

Otávio C.G. Baiocchi ◽

Ronald Pinheiro ◽

Adelson Alves

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Median Time ◽

Autologous Stem Cell Transplantation ◽

Clinical Characteristics ◽

Residual Disease ◽

High Dose

Abstract Introduction: autologous stem cell transplantation is a potentially curative or may augment the time to progression in Multiple Myeloma (MM) patients. The immunotherapy with rituximab may help control the minimal residual disease after high dose chemotherapy. Twenty percent (20%) of Multiple Myeloma patients express the CD20+ protein and can be target for immunotherapy. Objective: The aim of this study was to evaluate the use of rituximab after autologous stem cell transplantation for Multiple Myeloma. Patients and Methods: eight patients (4 male) with a median age of 53 (range 43–59) years diagnosed with MM. All of them had received at least one previous regimen were enrolled in the protocol study. All patients signed the consent form. Patients in relapse received a salvage regimen with C-VAD n=2 (cyclofosfamide 4 g/m2 e vincristine 0.4 mg/d (d 1–4), doxorrubicin 0.9 mg/m2 (d1-4) e dexametasone 40 mg (d1-4; 9-12; 17–22) or cyclofosfamide (1OO mg/kg, n=7) followed by stem cell harvesting. The preparative regimen was Busulfan 12 mg/kg and cyclofosfamide 120 mg/kg or Melphalan 200mg/m2. Rituximab at a dose of 375mg/m2 weekly x 4 was given every 6 months for 2 years after SCT. The clinical characteristics of the patients are shown on Table 1. Results: the median time to ANC and platelets engraftment was 11 (range 8–12) and 26 (range 17–35) days. Patients have been in CR at a median time of 11 months follow-up. Minor Rituximab-associated toxicities were seen:rigor, fever and short of breath that were controlled with acetaminophen and diphenidramine. Conclusion: the Rituximab given after autologous stem cell transplantation is safe in Multiple Myeloma patients and may prolong time to disease progression. A randomized study is required to evaluate the role of rituximab after ASCT. Table 1 - Clinical Characteristics of Patients Patients Age/gender Status Pre- BMT Status Post- BMT Salvage Tx Prep. regimen ANC/Platelets X1000 MM3/ml Follow-up (months) FRC 57/M PR PR C-VAD BU+MEL 12/28 EXPIRED MB 52/F CR1 CR1 C-VAD BU+MEL 12/60 EXPIRED AM 52/F PR PR C-VAD BU+MEL 9/26 EXPIRED IM 54/M PR CR Cyx2 BU+MEL 12/21 ALIVE GAD 50/F PR CR Cyx2 BU+MEL 12/35 ALIVE SCM 59/M CR CR Cyx2 BU+MEL 10/17 ALIVE MAD 63/F CR CR C-VAD MELPHALAN 12/25 ALIVE JFC 51/M CR CR C-VAD BU+MEL 12/18 ALIVE

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Allogeneic Stem Cell Transplantation in Angioimmunoblastic T-Cell Lymphoma (AITL): A Retrospective Survey from the Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT).

Blood ◽

10.1182/blood.v110.11.3042.3042 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3042-3042

Author(s):

Charalampia Kyriakou ◽

C. Canals ◽

G. Taghipour ◽

J. Finke ◽

H. Kolb ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

T Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Relapse Rate ◽

Allogeneic Stem Cell Transplantation ◽

Cell Lymphoma ◽

T Cell Lymphoma

Abstract AITL is a rare peripheral T-cell lymphoma characterised by an aggressive behaviour, which primarily affects the elderly. Chemotherapy regimens fail to alter the high relapse rate and overall survival hardly exceeds 25% at 5 years. To date, there is no information on the potential role of allogeneic stem cell transplantation (allo-SCT) in the management of AITL. We report the outcome of 39 patients with a median age of 47 years (24–68), who underwent an allo-SCT between 1995 and 2004 for AITL, and were reported to the EBMT registry. The median time from diagnosis to transplant was 10 months (4–72). Thirty-four patients (87%) had previously received two or more treatment lines, and 16 patients (41%) a previous autologous SCT. Fifteen patients (38%) had a primary refractory disease, 13 (33%) were transplanted in partial remission and the remaining patients were in complete remission (CR) (mostly in 2nd and 3rd CR). Twenty-four patients were transplanted from an HLA-identical sibling and 15 from a matched unrelated donor. A myeloablative conditioning regimen (MAC) was used in 21 patients (cyclophosphamide + total body irradiation in 14), while 18 patients received fludarabine-based reduced intensity conditionings (RIC). Peripheral blood was the source of stem cells in 35 patients (90%). Three patients failed to engraft (one patient in the RIC group). Twenty-one patients (54%) developed acute graft versus host disease (grade I-II, n=16; grade III-IV, n=5). Twenty-eight patients (72%) achieved a CR after the allogeneic procedure. Nine patients died from transplant related mortality (TRM) and 5 patients from disease progression. The cumulative incidence of TRM at 12 months was 19% for the MAC and 26% for the RIC group. After a median follow-up for the surviving patients of 20 months (6–74), 25 patients are alive. Relapse rates at 1 and 3 years were estimated at 10% and 18% for the MAC and 16 and 20% for the RIC patients. Progression free survival rates at 3 years were 67% and 50% and the overall survival at the same time 71% and 56% for the MAC and RIC group of patients, respectively. Although follow up is rather short, these data suggest that allo-SCT results in good overall response and is associated with a low relapse rate in this group of poor risk heavily pre-treated and rather elderly group of AITL patients. Allo-SCT could be considered a therapeutic option for eligible high-risk AITL patients. Nevertheless, the impact of this approach should be further explored in prospective collaborative studies.

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High Dose (HD-AraC) Vs Standard Dose Cytosine Arabinoside (SD-AraC) During Induction and IL-2 Vs Observation After Consolidation/Autologous Stem Cell Transplantation in Patients with Acute Myelogenous Leukemia (AML): Final Report of the AML-12 Trial of EORTC and GIMEMA Leukemia Groups on the Value of High Dose AraC

Blood ◽

10.1182/blood.v118.21.257.257 ◽

2011 ◽

Vol 118 (21) ◽

pp. 257-257 ◽

Cited By ~ 1

Author(s):

Roelof Willemze ◽

Stefan Suciu ◽

Franco Mandelli ◽

Giovanna Meloni ◽

Boris Labar ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Myelogenous Leukemia ◽

Phase Iii ◽

High Dose ◽

Treatment Difference

Abstract Abstract 257 The AML-12 randomized phase III trial of EORTC-LG and GIMEMA assessed the efficacy and toxicity of HD-AraC (3 g/sqm/12 hrs for 4 days) combined with daunorubicin (50 mg/sqm/d for 3 days) and etoposide (50 mg/sqm/d for 5 days) vs SD-AraC (100 mg/sqm/d for 10 days) with the same drugs, in previously untreated AML < 61 year old patients (APL excluded). Patients (pts) in complete remission (CR) had to receive consolidation consisting of AraC (500 mg/sqm/12 hrs for 6 days) and daunorubicin. Subsequently an allogeneic (allo-SCT) or autologous stem cell transplantation (auto-SCT) was planned according to donor availability and age. A 2nd randomization had to be done after evaluation of consolidation in pts without a donor: auto-SCT followed or not by low dose IL-2. The aim of the trial was to detect an 8% treatment difference (from 35% to 43%) in the 5-yr overall survival (OS) rate, corresponding to a hazard ratio (HR) of 0.80 (alpha=5%, power=95%); secondary endpoints were response to induction, toxicity, disease-free survival (DFS) from CR. Randomization was performed centrally; the 1st randomization was stratified for age (<46 vs > 45 yrs), performance status, WBC and center. Intent-to-treat analysis was done. From 9/1999 till 1/2008, 2005 pts from 68 centers were randomized. Due to insufficient reporting, 3 centers, who recruited 63 patients, have been excluded from the analysis. The remaining 1942 pts (872 pts entered by EORTC-LG and 1070 by GIMEMA) 969 were randomized in SD-AraC and 973 in HD-AraC arm; among them 25 and 28, respectively, were ineligible, but kept in the analysis. Both arms were comparable with respect to gender, age (median=45 yrs), disease history, initial leukocyte count, PS, FAB and cytogenetics. At a median follow up of 6 yrs, 1114 pts had died. Results: After 1 or 2 courses of induction, CR was achieved in 1430 pts (73.6%); 684 (71.9%) pts (SD-AraC group) vrs 746 (78.7%) pts (HD-AraC group): p=0.002. Resistance was documented in 173 (18.2%) vrs 123 (13%), and death during induction in 85 (8.9%) vrs 71 (7.5%) pts, respectively. Induction toxicity profile and grade was similar in the 2 arms except for conjunctivitis grade 3: HD-AraC>SD-AraC. CR rates for pts<46 yrs were 74.7% (SD-AraC) and 81.4% (HD-AraC) and for pts>45 yrs 66.4% (SD-AraC) and 71.8% (HD-AraC). 634 pts (SD-AraC and 686 (HD-AraC) received a consolidation cycle. Among 765 CR-pts<46 yrs 284 pts had an HLA identical sibling (<46D) and 481 did not or had not been typed (<46NoD). Among 665 CR-pts>45 yrs 225 pts had an HLA identical sibling (>45D) and 440 did not or had not been typed (>45NoD). In the <46D group 211 underwent an allo-SCT and 11 an auto-SCT. In the <46NoD group 274 underwent an auto-SCT and 29 a MUD-SCT; in the >45D group 147 underwent an allo-SCT and 14 an auto-SCT. In the >45NoD group 244 underwent an auto-SCT and 12 a MUD-SCT. Comparisons of treatments arm regarding OS from randomization, DFS and Survival (S) from CR are indicated in the Table. The impact of age on the treatment difference regarding OS was almost significant (p=0.06). In pts >45 who reached CR, the decrease in the relapse rate in the HD-Ara-C arm vrs SD-Ara-C arm (45.5% vs 49.4%) was counterbalanced by an increase in the death in CR rate (18.4% vs 13.2%). Conclusion: The final evaluation of the EORTC-GIMEMA AML-12 trial shows that, with a median follow-up of 6 years, HD-AraC in the induction treatment leads to a significantly higher CR rate than SD-Ara-C and results in improvement in overall survival but only in pts under the age of 46 years. Disclosures: Muus: Amgen: Membership on an entity's Board of Directors or advisory committees. Beksac:Janssen Cilag: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau.

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Cytomegalovirus Infection and Lymphopenia Are Associated with Increased Mortality Post Autologous Stem Cell Transplantation

Blood ◽

10.1182/blood.v120.21.4208.4208 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4208-4208

Author(s):

Alessandro de Moura Almeida ◽

Erika Maria Macedo ◽

Claudia Mac Donald Bley ◽

Fabio R. Kerbauy ◽

Paulo Vidal Campregher ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hodgkin’S Lymphoma ◽

Univariate Analysis ◽

Hodgkin's Lymphoma ◽

Prognostic Impact ◽

Cmv Infection

Abstract Abstract 4208 Introduction: Despite preventive and therapeutic antiviral medication cytomegalovirus (CMV) infection is still a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (SCT). Only limited data on CMV infection and disease are available in autologous SCT recipients. Previous studies have demonstrated that the probability of CMV infection is nearly 60% in seropositive patients and 23% in seronegative patients undergoing autologous SCT, but its impact in mortality is unclear. Methods: We retrospectively reviewed the medical records of 101 patients undergoing autologous SCT at Hospital Israelita Albert Einstein from January, 2005 to July, 2012. CMV infection was defined as a quantitative real time PCR assay showing greater than 165 copies and/or positive CMV pp65 antigenemia assay. Lymphocyte count was registered at 15th day after SCT and lymphopenia was defined as an absolute lymphocytes count (ALC) < 500 at that time point. Overall survival (OS) was estimated from the time of transplant until death, with surviving patients censored at last follow-up. Variables entered into the multivariate Cox analysis were those with a p-value <0.10 in the univariate analysis. CMV infection was analyzed as a time-dependent covariate, considering the time to CMV infection. Statistical analysis was performed with STATA (v11.0) and alfa error was defined as 5%. Results: The majority of patients were male (62.4%) and the median age was 58 years old (range: 3–76). Peripheral stem cell harvest was the main source of cells (92%). A positive serological CMV status was found in 93.75% of patients. Most common indications for autologous SCT were multiple myeloma (34%), non-Hodgkin's lymphoma (40%) and Hodgkin's lymphoma (6%). After a median follow-up of 2 years, the OS for the whole cohort was 61% (95% confidence interval [CI] 48–72%). CMV infection post SCT was seen in 26% of patients. In the univariate analysis, development of CMV infection and presence of D15 lymphopenia were associated with a higher mortality (CMV infection-hazard ratio [HR] 3.32 [95%IC 1.61–6.84]; p= 0.001; D15 lymphopenia- HR 2.37 [95% IC 1.11–5.05]; p= 0.024). Patients who developed CMV infection in the setting of D15 lymphopenia had the worse outcome (2-years OS 19%; 95% CI 9–43%; figure 1). D15 lymphopenia was not associated with a higher rates of CMV infection (p=0.41). In Cox multivariate analysis, lower overall survival was demonstrated in female patients (HR= 2.23, 95%IC 1.08–4.58; p= 0.029), in the presence of D15 lymphopenia (HR= 2.56, 95%IC 1.19–5.51; p= 0.016) and CMV infection (HR: 3.33, 95% IC1.61–46.86; p= 0.001). Conclusion: CMV infection post-autologous SCT is associated with a decreased survival, and in the concomitant presence of D15 lymphopenia appears to indicate a subgroup of patients with very poor outcome. It is possible that CMV infection does not lead directly to increased mortality, but is rather a surrogate marker of decreased immune function post-ASCT. Future studies should prospectively evaluate the incidence and prognostic impact of CMV infection post-ASCT and correlate with markers of immune recovery. Disclosures: No relevant conflicts of interest to declare.

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Third Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma

Blood ◽

10.1182/blood.v120.21.4548.4548 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4548-4548

Author(s):

Catherine Garnett ◽

Chrissy Giles ◽

Maialen Lasa ◽

Osman Ahmed ◽

Marco Bua ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Disease Progression ◽

Cell Transplantation ◽

Median Time ◽

Autologous Stem Cell Transplantation ◽

Autologous Stem Cell Transplant ◽

Cell Transplant

Abstract Abstract 4548 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma (MM). In the face of almost inevitable disease relapse, there is growing evidence for second ASCT as salvage therapy in certain patient groups. However, few published data exist regarding efficacy and safety of third ASCT in relapsed disease. We retrospectively analysed the results of eight patients treated at a single UK institution who each received three separate autologous stem cell transplants for relapsed MM between May 1997 and April 2012. There were four men and four women. Median age at diagnosis was 48 years (range, 25–64 years). Paraprotein isotype was IgA in two patients and IgG in the remaining six patients. At the time of 1st transplant, seven patients were in partial response (PR) and one in complete response (CR). Conditioning melphalan dose was 200mg/m2 in all but two patients who received 140mg/m2. Three patients entered CR following 1st transplant and four patients showed PR. Median time to disease progression was 31 months (range, 11.8–52.9 months). Prior to 2nd transplant, five patients achieved very good partial response (VGPR) and three PR with induction chemotherapy. Melphalan dose was 200mg/m2 in five patients and 140mg/m2 in the remaining three. Median time to disease progression was 22.3 months (range, 10.1– 39.6 months). At the time of 3rd transplant, two patients had achieved VGPR following induction chemotherapy, one showed PR, two stable disease (SD) and three evidence of disease progression. For the 3rd transplant, melphalan dose was reduced in most cases. Median follow up post 3rd transplant was 8.3 months (range 1.1–29.3 months). One patient died of overwhelming sepsis within one month of transplantation (treatment related mortality). At the time of analysis, five patients had relapsed following 3rd ASCT, with median time to disease progression of 10.4 months (range, 2.7–23.7 months). Three of these patients died at 3.5, 17.6 and 27.1 months post 3rd transplant. The remaining two patients are alive with no evidence of disease relapse (progression free survival (PFS) time of 3.3 and 1.3 months). Overall survival (OS) for the group from diagnosis is 62% at 10 years with a median OS from diagnosis of 149 months (range 68.5 – 189.2 months) (Figure 1). Median OS for the group from 3rd transplant is 17.6 months (range, 1.1–29.3 months) (Figure 2). Median PFS is 10.4 months (range 1.1–23.7 months). These results demonstrate that third ASCT is a possible treatment strategy for patients with relapsed MM and may prolong patient survival. Figure 1: Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 1:. Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 2: Overall survival from time of 3rd autologous stem cell transplant Figure 2:. Overall survival from time of 3rd autologous stem cell transplant Disclosures: No relevant conflicts of interest to declare.

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Reduced Intensity Vs. Myeloablative Conditioning Followed By Allogeneic Stem Cell Transplantation for Patients with Myelodysplastic Syndrome: Long Term Follow-up of a Prospective Randomized EBMT Phase III Study (RICMAC-Trial)

Blood ◽

10.1182/blood-2018-99-113340 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1019-1019

Author(s):

Nicolaus Kroeger ◽

Simona Iacobelli ◽

Linda Koster ◽

Dietger Niederwieser ◽

Uwe Platzbecker ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Research Funding ◽

Phase Iii ◽

Long Term Follow Up

Abstract Introduction Retrospective studies in MDS/sAML suggest that reducing the intensity of the conditioning regimen prior to allogeneic stem cell transplantation reduces the risk of non-relapse mortality but is associated with a higher risk of relapse. A higher risk of relapse after RIC was confirmed in a prospective BMT CTN study but the prospective randomized studies from the EBMT for MDS and sAML did not show a difference in outcome after 2 years (J Clin Oncol. 2017 Jul 1;35(19):2157-2164). Here we present a long term follow-up of the study after a median follow-up of 75 months (range 4-150 months). Methods Within the European Society of Blood and Marrow Transplantation (EBMT) we conducted a prospective, multicenter, open label, randomized phase III trial comparing comparing a busulfan based (Busulfan 8mg/kg orally or equivalent dosis intravenously (iv) plus fludarabin 180mg/m²) reduced intensity conditioning regimen (RIC) and a standard myeloablative busulfan (Busulfan 16mg/kg orally or equivalent dosis iv plus cyclophosphamide 120mg/kg) based regimen (MAC) in patients with MDS or sAML (<20 % blasts). Between May 2004 and December 2012, a total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1 : 1 ratio and stratified according to donor, age and blast count. Results In the first report (JCO 2017) the CI of NRM after 1 year was 17% (95% CI 8-26%) after RIC and 25% (95% CI 15-36%) after MAC (p = 0.29). The CI of relapse at 2 years was 17% (95% CI 8-26%) after RIC and 15% (95% CI 6-24%) after MAC (p = 0.6), resulting in a 2 year relapse-free and overall survival of 62% (95% CI 50-74%) and 76% (95% CI 66-87%) after RIC and 58% (95% CI 46-71%) and 63% (95% CI 51-75%) after MAC (p = 0.58 and p = 0.08, respectively). In the current follow-up study, all cases but one who were alive at last report could be updated. The median follow-up is now 75 months in the MAC and 72 months in the RIC arm. Since last follow-up =18 death occurred in both arm (MAC n=8, RIC n=10) 8 relapses (MAC n=4; RIC n=4) and 6 NRM (MAC n=2; RIC n=4). Second allogeneic stem cell transplantation was performed in 18 patients (n=10 in RIC and n=8 in MAC) due to graft failure (n=4) relapse (n=11) and others (n=3). The CI of chronic GvHD at 5 years was 65% (95% CI: 53-78) after RIC and 68% after MAC ((95% CI: 55-81; p = 0.70). At 5 years there was no difference in CI of NRM (22%, 95%CI: 12-32 vs 30% , 95%CI : 19-42, p=0.5) in CI of Relapse (22% , 95% CI: 12-32 vs18%, 95% CI: 8-28, p= 0.7), Relapse free- (57%, 95% CI: 44-69 vs51%, 95% CI: 39-64, p=0.8) and Overall survival (69%, 95% CI: 58-80 vs 53%, 95% CI: 40-65, p=0.15) between RIC and MAC, respectively. Conclusion This long term follow-up of the prospective randomized EBMT trial confirmed early results that RIC resulted in at least similar long term relapse-free and overall survival as MAC in patients with MDS or sAML. The trial was registered under ClinicalTrials.gov Identifier: NCT01203228. Disclosures Niederwieser: Miltenyi: Speakers Bureau; Novartis: Research Funding. Platzbecker:Celgene: Research Funding. Scheid:Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria. Stelljes:MSD: Consultancy; Amgen: Honoraria; JAZZ: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Honoraria. Heim:Novartis: Research Funding. Bethge:Miltenyi Biotec GmbH: Consultancy, Honoraria, Research Funding; Neovii GmbH: Honoraria, Research Funding. Kobbe:Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Other: Travel Support, Research Funding.

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Outcome after second stem cell transplantation for relapsed multiple myeloma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.8118 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 8118-8118 ◽

Cited By ~ 2

Author(s):

L. Simpson ◽

R. Verma ◽

S. Kumar ◽

M. Lacy ◽

A. Dispenzieri ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Median Time ◽

Standard Of Care ◽

Best Response ◽

High Risk Disease ◽

Viable Approach ◽

Median Interval

8118 Background: Autologous stem cell transplantation (ASCT) improves survival and remains the standard of care for patients with newly diagnosed myeloma considered eligible for transplant. However, ASCT is not curative and patients relapse after a median interval of 24–30 months. While new therapeutic options have become available for relapsed MM, repeat ASCT remains an option especially when previously collected stem cells are available. The outcome of pts going to a second SCT in the relapsed setting has not been studied extensively. Methods: We identified pts with myeloma who received a second SCT from a prospectively maintained database. Planned tandem ASCTs were excluded. 56 pts received a second SCT for relapsed MM, including 11 allogeneic SCTs. Among the 45 second ASCTs, 5 were followed by reduced intensity allogeneic SCT and were analyzed with the allogeneic group. Results: The median age at second ASCT was 60.2 yrs (range, 41.3–74.4) and 27 (68%) were males. The median time to second ASCT from diagnosis, first ASCT and relapse were 47.4 mos (22.8–158.6), 36.3 mos (13.5–129.8) and 7.2 mos (1–32) respectively. Among patients receiving second APBSC, 14 (35%) patients were alive with a median follow up of 10.5 mos (1–45 mos). All patients received melphalan conditioning. The median time to neutrophil engraftment was 15 days and platelet engraftment was 16 days. The median hospitalization was 4 days (range 0–33) and there was one transplant related death in the group. The best response included 13 pts with CR (33%), 4 with VGPR (10%), and 19 with PR (48%). MM has relapsed in 22 (55%) pts with a median PFS of 12.5 mos from second ASCT. The median estimated OS from diagnosis, first ASCT and second ASCT were 100.5 mos, 65.9 mos, and 30.6 mos respectively. Among the 16 pts receiving allogeneic SCT, 8 pts (50%) were alive at analysis with a median PFS and OS from transplant of 17.9 mos and 33.5 mos respectively. Conclusions: Second ASCT as salvage therapy for relapsed MM is a viable approach and has a favorable outcome in this selected group of patients. The toxicity, engraftment kinetics, hospitalization and the response rates are comparable to patients undergoing initial ASCT. Allogeneic SCT with or with out a preceding ASCT results in comparable survival in selected patients with high risk disease. No significant financial relationships to disclose.

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