Comorbidities Index Is Not Predictive of Treatment Related Mortality in Patients (pts) Older Than 60 Years Treated with Reduced Intensity Conditioning and Allogeneic Stem Cell Transplantation (RIC-ALLO).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1180-1180
Author(s):  
Luca Castagna ◽  
Sabine Furst ◽  
Jean El Cheikh ◽  
Catherine Faucher ◽  
Mohamad Mohty ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Viral Infections ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Abstract 1180 Poster Board I-202 Benjamin Esterni, Didier Blaise Background: Allogeneic stem cell transplantation (ALLO) is the only curative therapy for many hematological malignancies. For many of these diseases, the median age at diagnosis is around the sixth decade of life, precluding myeloablative ALLO (MAC-ALLO). RIC-ALLO is less toxic and it has been performed in elderly pts, mainly affected by acute leukemia. Finally, comorbidities index seem to predict treatment related mortality (TRM) and overall survival (OS). Patients and methods: From 2001 and 2008, 67 pts older than 60 years (median age 63 y, range 60-70) received RIC-ALLO. Diseases were: acute myeloid leukemia 45%, multiple myeloma 18%, chronic lymphocytic leukemia 12%, non-Hodgkin lymphoma 10%, myelodysplasia 6%, plasmacellular leukemia 3%, others 6%. Disease status at RIC-ALLO was: complete remission 54%, partial remission 16%, and active disease 30%. RIC consisted of fludarabine-based with thymoglobulin 64%, or low-dose TBI-based 36%. Donors were: HLAid sibling 73%, matched unrelated 21%, and cord blood 6%. Previous autologous transplant was performed in 59% of pts. The median number of CD34+ and CD3+ cells infused was 5 (range 1-9.4) and 296 (range 84-704), respectively. Karnofski score was 60-80% in 25% and 90-100% in 75%; HCT-CI was 0 in 33%, 1-2 in 33%, and more than 3 in 34%; PAM score was 8-16 in 9%, 17-33 in 65%, 24-30 in 22%, and more than 31 in 3%; EBMT score was 2 in 22%, 3 in 36%, 4 in 28%, more than 5 in 12%. Results: The median follow-up was 22 months. The 2-y OS and PFS were 66.8% (IC95 [55.5-80.4]) and 52.4% (IC95 [39.5-69.5]), respectively. Grade II-IV acute graft versus host disease (aGVHD) and chronic GVHD (cGVHD) incidence were 49% and 43%, respectively. Early infections were fever of unknown origin in 42% of pts, bacterial infection in 6 cases, pneumonia in 8, and viral infections in 14. The early infection-related mortality was null. Late infections were bacterial in 3 cases, pneumonia in 1, viral infections in 6, and candidemia in 1. Seven pts died from late infective complications. Overall, the cause of death was toxicities in 18 pts and disease progression in 6 pts. The 100-d and 1-y TRM were 6.35% (IC95 [0.278-12.4]) and 24.2% (IC95 [12.9-35.4]), respectively. In univariate analysis, HCT-CI, EBMT score, and PAM score did not influence TRM or OS. Furthermore, age (60-65 vs 66-70) was not related to TRM. Conclusions: The aim of this retrospective study was to verify if TRM was excessively high in elderly pts, affected from several haematological diseases and receiving ALLO from different donors and after different RIC. A secondary objective was to evaluate if several comorbidities index could predict TRM and OS. This heterogeneity should be regarded as a more realistic view of general population. TRM was acceptable and not different when compared to younger pts as reported in literature. Furthermore, neither comorbidities index nor age help segregate a group of pts with different TRM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Allogeneic stem cell transplantation in follicular lymphoma: recent progress and controversy

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 610-618 ◽  
Author(s):  
Koen van Besien
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Performance Status ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Allogeneic stem cell transplantation (allo HCT) is a curative treatment for follicular lymphoma, but is hampered by a relatively high treatment-related mortality and by difficulties in identifying high-risk groups for whom transplant is warranted. Results with myeloablative conditioning have improved, but the field has shifted largely to reduced-intensity conditioning and non-myeloablative transplantation, though morbidity and mortality are also substantial. Some groups have investigated T cell–depleted transplantation, which results in a low rate of chronic graft-versus-host disease (GVHD) and, in most studies, excellent rates of disease control. Overall, outcome after alloHCT for follicular lymphoma correlates more with disease status, with performance status and with comorbidities than with any particular conditioning regimen used. For patients with chemotherapy-sensitive disease, the treatment-related mortality has stabilized in the 15% to 20% range and, depending on the method of GVHD prophylaxis and the donor type, there is an additional 20% to 60% incidence of chronic GVHD. For patients with chemotherapy-refractory disease, both treatment-related mortality and recurrence rates are much higher, but their prognosis is dismal with other treatments and some may be cured, particularly with myeloablative transplants. Ongoing studies focus on improving conditioning regimens, on prevention of disease recurrence and on decreasing chronic GVHD.

scholarly journals Allogeneic Stem Cell Transplantation with Immunodepleted Grafts for Lymphoproliferative Malignancies

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1252-1252
Author(s):  
Nicolas Novitzky ◽  
Valda Thomas
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Ex Vivo ◽  
Univariate Analysis ◽  
Disease Recurrence ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Introduction: The treatment of lymphoproliferative disorders that fail initial therapy remains unsatisfactory. Allogeneic stem cell transplantation can be curative but has been associated with high treatment related mortality, particularly from graft vs. host disease (GvHD). Immunodepletion of the peripheral blood stem cell (PBSC) graft with alemtuzumab effectively prevents GvHD. Methods: Patients with lymphoma (excluding diffuse large B-cell) in second or subsequent response were offered allogeneic stem cell transplantation if they had a human leukocyte antigen (HLA) compatible donor. Haematopoietic stem cells were mobilized with filgrastim (5-10 ug/kg) and PBSC were collected by apheresis. Patients were conditioned with myeloablative doses of chemotherapy or radiotherapy. For GvHD prophylaxis mobilized donor blood stem cells were incubated ex vivo with alemtuzumab (in the bag) for 30 minutes and infused intravenously. Post transplantation patients received therapeutic blood levels of cyclosporine until day 90. The end points of the study were frequency of GvHD, transplant mortality, disease recurrence and overall survival (OS) rates. Results: Sixty one consecutive patients with lymphoma (follicular 17, marginal zone 2, Waldestrom’s macroglobulinaemia 2, transformed 16, peripheral T-cell 16 [all ALK negative] and lymphoblastic 8) underwent allogeneic transplantation. None had received a previous transplant. PBPC were from siblings in 53 patients and 8 from unrelated donors. Twenty patients were female and the median age was 47 years. The median CD34+ cell number infused was 4.71 (1.31 – 17.88) x10^6/kg. The median dose of alemtuzumab added into the bag was 10 mg. All recovered the blood counts at median of 13 days. Seventeen (28%) patients died, 11 (18%) of transplant related causes. Chimerism studies performed in 42 patients showed full donor chimerism in each case. GvHD (> grade 1) was seen in 8 patients (13%). Cytomegalovirus reactivation occurred in 21% but all responded to gancyclovir. Seventeen patients died, 11 (18%) of treatment related complications. Eight patients had disease recurrence, two of three achieved further response after donor leukocyte infusion and six died of the malignancy. At median follow up of 2260 15-4412) days 71% are alive in response. There was no difference in survival among the 4 histological groups or between chemotherapy and radiotherapy based conditioning. In univariate analysis female donor gender (for male patients) and GvHD were significant adverse factors for survival. Cox analysis showed that occurrence of GvHD (p= 0.001) was an independent significantly adverse factor for survival. Conclusions: We conclude that ex vivo immunodepletion of grafts with alemtuzumab leads to reduced rates of GvHD and results in lesser treatment related mortality despite myeloablative conditioning. Recurrence rates appear low suggesting that in the absence of GvHD prescribing dose intense conditioning and allogeneic stem cell transplantation earlier, before the malignancy is refractory, could be an effective strategy for patients with advanced lymphoma. Disclosures No relevant conflicts of interest to declare.

Pharmacokinetic Dose Guidance of IV Busulfan with Fludarabine with Allogeneic Stem Cell Transplantation Improves Progression Free Survival in Patients with AML and MDS; Results of a Randomized Phase III Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 892-892 ◽  
Author(s):  
Borje S Andersson ◽  
Marcos J de Lima ◽  
Rima M Saliba ◽  
Elizabeth J Shpall ◽  
Uday Popat ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Progression Free Survival ◽  
Fixed Dose ◽  
Free Survival ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Abstract 892 The myeloablative, reduced toxicity regimen, IV Busulfan (Bu) and fludarabine (Flu), is effective conditioning for allogeneic stem cell transplantation for treatment of patients with AML and MDS. We performed a prospective randomized study to optimize the antileukemic cytoreduction of this regimen, testing the hypothesis that pharmacokinetically (PK-) guided IV Bu-dosing to an average daily AUC of 6,000 μMol-min yields improved leukemia-free survival compared with a fixed IV Bu dose of 130 mg/m2, which gives a median AUC of approximately 5000 μMol-min. The study was approved by the M.D. Anderson Cancer Center IRB and all patients provided informed consent. 139 patients were in a first or second complete remission (CR), 86 were not in remission, including patients with marrow remission but with incomplete hematologic recovery (CRi) or with active disease. Median age was 50 years (range 13–65). 51% received a transplant from a related donor and 49% had unrelated donors. 28% patients received bone marrow and 72% PBPC grafts. Disease characteristics are summarized in the following table. Median follow-up of surviving patients was 25 months (2–66). The patients receiving PK guided busulfan dosing had significantly better progression free survival at 3 years than the fixed dose group, 56% (45–66%) vs. 42% (32–52%) P=0.03, as well as lower cumulative incidence of progression 23% (16–34%) vs. 35% (27–46%) p=0.03. Overall survival at 3 years for the two groups was 57% (46–68%) vs 47% (36–57%) p=0.2. The greatest effect was seen in patients not in remission at the time of transplant. The cumulative incidence of disease progression for the PK Guided and Fixed dose groups was 20% and 25% in patients transplanted in remission (P=0.5), and 29% and 50% for patients transplanted not in remission (P=0.03). Major outcomes are summarized in the following table. There was no significant difference in toxicity pattern, incidence of acute GVHD or treatment related mortality between the PK-guided/adjusted and fixed- dose groups. In multivariate analysis, poor risk cytogenetics and flt3 mutation was associated with inferior PFS. In conclusion, administration of higher dose intravenous busulfan using pharmacokinetic dose guidance targeting an AUC of 6000 μMol-min combined with fludarabine improved progression free survival in patients undergoing allogeneic stem cell transplantation for treatment of AML and MDS, without increasing the risks for serious toxicity and treatment-related mortality. Disclosures: Andersson: Otsuka: Consultancy, MD Anderson Cancer holds a patent on busulfan. Off Label Use: Busulfan for conditioning for AML. Popat:Otsuka: Research Funding. Jones:Otsuka: Membership on an entity's Board of Directors or advisory committees. Nieto:Otsuka Corp: Research Funding. Kebriaei:Otsuka: Research Funding. Worth:Otsuka Corp: Research Funding. Champlin:Otsuka Corp: Research Funding; NCI CA55164: Research Funding.

The Impact of ATG/Alg in Preconditioning On the Allogeneic Stem Cell Transplantation for Patients with Acute Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4185-4185
Author(s):  
Koji Kato ◽  
Yoshiko Atsuta ◽  
Kazuteru Ohashi ◽  
Takahiro Fukuda ◽  
Shuichi Taniguchi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Cell Sources ◽  
The Impact

Abstract Abstract 4185 Background: Since the clinical implication of anti-lymphocyte globulin (ATG/ALG) in allogeneic stem cell transplantation (allo-SCT) is not fully understood, we tried to identify the clinical impact of ATG/ALG in patients with acute leukemia who received allo-SCT in Japan. Patients and Methods: We analyzed patients with ALL (n=5494) and AML (n=8115) who received first allogeneic SCT from 1983 to 2009 with (n=356) or without (n=13253) ATG/ALG. Their stem cell sources were bone marrow (BM, n=9056), peripheral blood (PB, n=1918), and cord blood (CB, n=2575) and they were transplanted at 1st complete remission (CR1, n=5681), 2nd CR (CR2, n=2495), and advanced stages (>CR3, n=5033). Results: Five year overall survival (5y OS) of all patients with or without ATG/ALG was 33.6% vs 44.5%, respectively (P<0.001) and multivariate analysis showed that ATG/ALG significantly reduced acute GVHD (P<0.001, HR=1.980) as well as chronic GVHD (P<0.001, HR=1.894). According to stem cell sources, 5y OS with or without ATG/ALG was 35.8% vs 47.5% (P<0.001) in BM, 34.7% vs 37.6% (P=0.067) in PB and 18.3% vs 39.9% (P<0.001) in CB. By multivariate analysis, ATG/ALG significantly reduced A-GVHD (P=0.005, HR=1.565) but decreased OS (P=0.004, HR=0.729) in BM, it reduced A-GVHD (P<0.001, HR=2.376) and C-GVHD (P<0.001, HR=2.691) but lowered engraftment (P=0.046, HR=0.810) in PB, and it increased TRM (P=0.004, HR=0.437) with decreased OS (P=0.011, HR=0.576) in CB. In Haplo transplantation (SCT from 2 or 3 antigens of HLA mismatched family donor, n=337), multivariate analysis showed that ATG/ALG did not affect the relapse, TRM and OS but, it significantly lowered engraftment (P=0.002, HR=0.602), and reduced A-GVHD (P<0.001, HR=2.622) as well as C-GVHD (P<0.001, HR=3.834). In contrast to these results, ATG/ALG did not affect the relapse rate irrespective of stem cell source or diagnosis. Conclusion: In allogeneic stem cell transplantation for patients with ALL and AML, ATG/ALG contribute in reducing acute and chronic GVHD without affecting relapse rates but it was a risk factor of OS for patients who received BM or CB. Disclosures: No relevant conflicts of interest to declare.

Epigenetic Modulation and Other Options to Improve Outcome of Stem Cell Transplantation in MDS

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Nicolaus Kröger
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Histone Deacetylase Inhibitors ◽  
Remission Status ◽  
Epigenetic Modulation ◽  
Effective Drugs ◽  
Treatment Related Mortality ◽  
Related Mortality

AbstractAllogeneic stem cell transplantation can cure patients with myelodysplastic syndromes. However, more than 50% of the patients who underwent allogeneic stem cell transplantation have failed to benefit from this treatment approach either due to treatment-related mortality or to relapse. The introduction of toxicity or dose-reduced conditioning has significantly reduced the treatment-related mortality but did not affect the risk of relapse. New effective drugs, such as hypomethylating agents, histone-deacetylase inhibitors or lenalidomide, can be used alone or in combination to improve the pretransplant remission status before allogeneic stem cell transplantation or after transplantation to prevent relapse as maintenance or consolidation therapy. This review will focus on these new possibilities and give some perspectives as to how the results of allogeneic stem cell transplantation can be further improved

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