scholarly journals Low Hemoglobin and Creatinine Clearance Correlate with Worse Overall Survival, Treatment-Related Mortality, and Regimen-Related Toxicities in Patients Receiving Allogeneic Stem Cell Transplantation with Fludarabine and Melphalan Conditioning

2020 ◽  
Vol 26 (3) ◽  
pp. S153-S154
Author(s):  
Karen Sweiss ◽  
Gregory Calip ◽  
Jeremy Johnson ◽  
John P. Galvin ◽  
Damiano Rondelli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Creatinine Clearance ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Treatment Related Mortality ◽  
Related Mortality

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.

“ATG16 L1 a Additional Risk Factor for TRM After allogeneic Stem Cell Transplantation”.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1155-1155
Author(s):  
Karin Landfried ◽  
Martin Hausmann ◽  
Gerhard Rogler ◽  
Daniel Wolff ◽  
Anne M Dickinson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Innate Immunity ◽  
Risk Factor ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Genetic Risk ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Abstract 1155 Poster Board I-177 Introduction A genome wide association scan of DNA polymorphisms identified association of a threonine-to-alanine substitution (T300A) in the autophagy-related 16-like gene ATG16 L1 as a new genetic risk factor of Crohn's disease. As our group had previously reported SNPs of another innate immunity receptor important in Crohn's disease, NOD2/CARD15, as a risk factor of severe graft-versus-host disease (GvHD) and treatment related mortality (TRM) following allogeneic stem cell transplantation (SCT), we now assessed the role of ATG16L in complications following SCT. Material and Methods A total of 127 HLAidentical sibling donor/recipient pairs were included. DNA from donors and recipients were analyzed for the ATG16L1 polymorphism and presence or absence of NOD2/CARD15 variants as previously published. Results of ATG16L1 and NOD2/CARD15 were correlated with clinical characteristics and outcome data, which were documented in a SPSS 17 database. The role of polymorphisms in GvHD III/IV was assessed by cross tabs, treatment related mortality (TRM) and overall survival were assessed by Kaplan Meier analysis. All patients and donors gave informed consent to analysis of genetic risk factors of GvHD. Results In 15 (12%) both recipient and donor were wildtype ATG16L1, in 25 (19%) either donor or recipient had the variant; and in 87 (69%) both donor and recipient had the variant. In 34 pairs, additional NOD2/CARD15 SNPs were observed. Severe GvHD occured in 6%, if both donor and recipient were ATG16L1 wildtype but increased to 22% if donor or recipient had the variant. Treatment related mortality increased in the presence of a donor variant (16% versus 46%, p 0.03) or if both; recipient and donor had variants (21% vs 48%, p 0.03). There seemed to be a gene dose effect for TRM, which was 13% if both were wildtype, 27% in the presence of either a donor or recipeint varaint and 48% if both had the variant (p≤ 0.05). Overall survival was not significantly different between these groups. In multivariate analysis, presence of ATG16L1 variant in both, donor and recipient was an independent risk factor for treatment related mortality when compared with age and stage of underlying disease (Hazard ratio 2.5, 95% confidence interval 1.1 – 6.1). Additional presence of NOD2/CARD15 variants seemed to be additive: TRM rose from 36% in recipients with ATG16L1 variant to 59% in the presence of additional recipient NOD2/CARD15 variants and from 34% in donors with ATG16L1 variants to 64%, if donors had additional NOD2/CARD15 SNPs. Conclusions As reported ATG16L1 polymorphism is a genetic risk factor for inflammatory bowel disease. In our work ATG16L1 polymorphism seems also to contribute to increased TRM in patients receiving allogeneic SCT. An accurate analysis of the causes of death is still accomplished. Altogether the data underline the role of the innate immunity and the disturbed antibacterial defense in the pathophysiology of transplant-associated complications. 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.

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

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.

Favourable Overall Survival with Myeloablative Allogeneic Stem Cell Transplantation for Follicular Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3005-3005
Author(s):  
John Kuruvilla ◽  
Qikun Bao ◽  
Erica Messner ◽  
Vikas Gupta ◽  
Thomas L. Kiss ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Disease Control ◽  
Allogeneic Stem Cell Transplantation ◽  
Unrelated Donor ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Introduction Allogeneic stem cell transplantation (Allo-SCT) remains an option for patients with follicular lymphoma (FL). Our program employs a strategy using allo-SCT for patients (pts) with high risk disease based on clinical characteristics. We performed a retrospective analysis to examine long-term disease control and treatment-related mortality. Methods 41 pts with indolent FL (follicular small cleaved [FSC], follicular mixed [FM] or FL grade 1,2 by WHO criteria) underwent allo-SCT at our institution between Jan 1989 and Dec 2005. Patients were in a chemosensitive remission at the time of SCT. The conditioning regimen consisted of busulfan (1 mg/kg PO q6h X4 days between 1989–200 and 3.2 mg/kg IV daily X 4days subsequently) and cyclophosphamide 60 mg/kg X 2 days. Cyclophosphamide 60 mg/kg X 2 days and TBI 12 Gy was used for unrelated donor SCT. GVHD prophylaxis was with cyclosporine A and methotrexate. Results There were 21 males and 20 females. The median age at the time of transplant was 45 years (range 24 to 58). Histologic subtype was: unclassified indolent FL: 3, Grade 1 or FSC: 17, Grade 2 or FM: 21. The median number of prior chemotherapy regimens was 2 (range 1 – 6) and was unavailable in 5. Prior anthracycline: 37, prior purine analog: 9, prior platinum-based: 20, prior auto-SCT: 1, prior rituximab: 11. The median time from diagnosis to allo-SCT was 23 months (range 6 – 161). 38 pts received BuCy conditioning. 2 patients underwent RIC SCT. Graft source was: matched related (MRD) bone marrow (BM): 28, MRD peripheral blood stem cells (PBSC): 4, Mismatch related (MMRD) bone marrow (BM): 1, MMRD PBSC: 2, matched unrelated donor (MUD) BM: 1, MUD PBSC: 1, and syngeneic BM: 4. The five year overall survival is 77% (95% confidence intervals 73 – 91%) with a median follow-up of 48 months post-SCT. Treatment-related mortality was 5 of 41 pts (12%). Non-relapse mortality was seen in one patient (3%). One patient has relapsed at over 3 years post-SCT while all recipients of syngeneic SCT remain in remission. Conclusions These results demonstrate that in selected patients, a fully myeloablative allo-SCT utilizing Busulfan-Cyclophosphamide conditioning provides excellent overall survival and disease control with low TRM. Prospective comparisons of RICSCT with myeloablative SCT should be performed in order to better evaluate these strategies.

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