Busulfan and Fludarabine Conditioning Regimen Negates the Impact of Comorbidity Score on Nonrelapse Mortality in Patients with AML/MDS

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 799-799
Author(s):  
Uday Popat ◽  
Rima Saliba ◽  
Leandro de Padua Silva ◽  
Borje S Andersson ◽  
Amin M Alousi ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
Unrelated Donor ◽  
Comorbidity Score ◽  
Cart Analysis ◽  
Reduced Toxicity ◽  
The Impact ◽  
Primary Predictor

Abstract BACKGROUND: Comorbidities as measured by newly developed Hematopoietic cell transplantation specific comorbidity index (HCT-CI) increases non relapse mortality in patients with hematological malignancies undergoing allogeneic transplantation. Whether this applies to recently treated patients with newer reduced toxicity regimens is not known. To evaluate this, we studied the factors influencing non relapse mortality in patients with AML/MDS. METHODS: 840 consecutive patients with AML/MDS undergoing allogeneic transplantation between January 1996 and April 2008 from a matched related or unrelated donor at our institution were studied. Information about disease characteristics, treatment, and outcomes was prospectively recorded in the departmental database. Comorbidities were retrospectively scored as previously described (Sorror et al Blood106: 2912–2919, 2005). Predictors of non-relapse mortality(NRM) at 2 years post SCT were evaluated on univariate analysis using Cox’s proportional hazards model and included age, sex, disease status at transplant, donor type, graft type, conditioning regimen (reduced intensity, ablative IV Busulfan(Bu) and Fludarabine(Flu), all other ablative regimens), and HCT-CI comorbidity score. Factors significant at the 0.1 level on univariate analysis were considered for classification and regression tree analysis (CART) to adjust for confounding and interaction effects. Statistical significance was defined at the 0.05 level, and cells including less than 10 patients were considered terminal in the CART analysis. RESULTS: There were 470(56%) males and 370(44%) females with a median age of 50 (range 18–77) years. 21% of patients were older than 60 years. HCT-CI comorbidity scores were as follows: 0 in 16% of patients, 1 in 13%, 2 in 13%, 3 or more in 58%. Donors were matched related for 58% of patients and unrelated for 42%. At the time of transplant, 22% of patients were in first complete remission (CR), 15% in second or third CR, and 63% had active disease. 36% of patients had reduced intensity conditioning regimen; 39% had myeloablative regimen consisting of Flu and Bu, and the remaining 25% had other myeloablative regimens. Cumulative incidence of NRM at 2 years was 26% (23–30). Univariate analysis showed that age > 60 (HR 1.6; p 0.002), disease status beyond first complete remission (HR 2.7; p <0.001), matched unrelated donor (HR 1.6; p 0.001), regimen other than Flu/Bu (HR 2.6; p<0.001), and a comorbidity score greater than 2 (HR 1.4; p 0.03) were associated with higher NRM. CART analysis (fig) showed that the use of Flu/Bu conditioning was the primary predictor of lower NRM. Age older than 60 years was the only additional significant predictor of NRM in patients who received Flu/Bu (HR 3.1; p 0.01). In patients who did not receive Flu/Bu, disease status at transplantation was the primary predictor of NRM with CR1 patients having a significantly lower incidence of NRM (CI =16%). The impact of donor type was only significant in patients who were not in CR1 with recipients of a matched related graft having a significantly lower NRM (CI=29%) than recipients of a matched unrelated graft (CI=46%). Comorbidity score did not significantly predict outcome in this analysis. CONCLUSION: Flu/Bu, a fully ablative reduced toxicity conditioning regimen, results in very low NRM, nullifying the impact of comorbidities. Figure Figure

scholarly journals Impact of Amotosalen/UVA Pathogen Inactivated Platelet Components on Outcomes after Allogeneic Hematopoetic Stem Cell Transplantation: A Single Center Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1167-1167
Author(s):  
Andreas S. Buser ◽  
Laura Infanti ◽  
Andreas Holbro ◽  
Joerg Halter ◽  
Sabine Gerull ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Risk Scores ◽  
Employment Equity ◽  
Stem Cell Source ◽  
Equity Ownership ◽  
The Impact

Background: Platelet component (PC) transfusion is required for allogeneic hematopoietic stem cell transplantation (HCT) recipients. Contamination with infectious pathogens (bacteria, viruses, or protozoa) and T-cells is a risk factor for transfusion-transmitted infection (TTI) and transfusion associated graft-versus-host disease (TA-GVHD). Pathogen inactivation (PI) treatment of PC with amotosalen-UVA (PI-PC, INTERCEPT Blood System, Cerus Corp) in platelet additive solution (PAS) without bacterial screening, gamma irradiation, CMV serology, and with 7-day storage has been the standard of care in Switzerland since 2011 to manage risk of TTI and TA-GVHD. PI-PC have replaced conventional PC (C-PC) prepared in PAS with gamma irradiation and 5 day storage. We previously reported platelet usage in two consecutive five year periods at the University Hospital of Basel. Mean PI-PC dose was higher (3.0 vs. 2.8 x 1011, p=0.001) and mean storage duration longer (4.2 vs. 3.4 days: p=0.001) than with C-PC. PC expiration wastage was reduced with 7-day PI-PC storage vs. 5-day storage (1.5% vs. 8.7%). For HCT recipients, days of PC support; PC use per patient; and RBC use per patient were similar, despite 24.3% lower corrected count increments (CCI) with PI-PC. Now, we report the impact of these observations on treatment related mortality (TRM) and overall survival (OS) 100 days after HCT. Patients and Methods: A two-period retrospective cohort study was conducted to evaluate PI-PC impact on outcomes of consecutive first allogeneic HCT recipients from January 2006 to December 2010 (Period 1, P1), when gamma-irradiated apheresis C-PC were used, and Period 2 (P2) from January 2011 to December 2017, when apheresis and whole blood-derived PI-PC were used. The review utilized 100-day OS and 100-day TRM to determine the impact of PI-PC on HCT outcomes. Descriptive statistics were used for continuous variables and log-rank analysis for survival outcomes. Univariate analysis was performed using Pearson χ2 statistics. Multivariate Cox regression modelling analyses included: PC period (P1, P2), donor match (HLA identical/twin, matched related, matched unrelated), disease state (early, intermediate, late), and conditioning regimen (reduced intensity, myeloablative) with TRM as the outcome. This was an IRB approved single-center analysis. Results: In P1 and P2, 256 and 557 consecutive first-time allogeneic HCT recipients were included, respectively. By univariate analysis, the distribution of European Group for Bone Marrow Transplantation (EBMT) risk scores (grouped 0-2, 3-4, 5-7) and mean patient age were higher during P2 (p = 0.001 and p <0.001, respectively). Primary disease status (p = 0.039); stem cell source (p <0.001); GVHD prophylaxis with ATG (p <0.001); total body irradiation (p <0.001); and conditioning regimen (p <0.001) were different between P1 and P2. Donor match (p=0.084) and disease status (p = 0.628) were similar in P1 and P2. TRM at day 100 post HCT was significantly less (31/557, 5.5%) for PI-PC recipients in P2 vs. C-PC recipients in P1 (37/256, 14.5%, p<0.001). Overall proportion of survivors at day 100 post HCT was significantly greater for PI-PC recipients (507/557, 91.0 %) compared to C-PC recipients (209/256, 81.6%, p <0.001). By multivariate Cox regression analysis, P2 with PI-PC component support was associated with improved TRM (p = 0.001; adjusted hazard ratio 0.433; 95% confidence interval: 0.262, 0.716). Donor match (p = 0.019), disease state (p = 0.022), and myeloablative conditioning (p = 0.034) were associated with significantly poorer TRM (Table). Stem cell source was not significant (p=0.157) in the model. Hemorrhage was reported as cause of death in 1/50 (2.0%) patients during P2 with PI-PC and 4/47 (8.5%) patients during P1 with C-PCs. Conclusions: Universal implementation of PI-PC in routine with extended storage to 7 days in P2 was associated with reduced TRM and better overall survival 100 days post HCT, despite transplantation of older patients with higher EBMT risk scores. Multivariate analysis revealed an adjusted hazard ratio of 0.433 (95% C.I. 0.262, 0.716) for TRM by 100 days, suggesting better outcomes in P2. This retrospective analysis at a single site indicated that PI-PC treated with amotosalen /UVA stored up to 7 days did not have a negative impact on TRM and OS in HCT recipients, and was an integral part of improving clinical outcomes at our institution. . Table. Disclosures Heim: Novartis: Research Funding. Irsch:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.

Haploidentical Transplantation (HAPLO) with Post-Transplant High-Dose Cyclophosphamide for Graft Vs Host Disease (GVHD) Prevention in the Treatment of High Risk Hematological Neoplasms

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4545-4545
Author(s):  
Jorge Gayoso ◽  
Mi Kwon ◽  
David Serrano ◽  
Pascual Balsalobre ◽  
Javier Anguita ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
High Dose ◽  
Unrelated Donor ◽  
Haploidentical Transplantation ◽  
Gvhd Prophylaxis

Abstract Abstract 4545 Introduction: Allogeneic transplantation is the only curative option in the treatment of multiple high risk hematologic neoplasms. Only 25–30% of patients have an HLA identical sibling donor and searching for a compatible unrelated donor or cord blood renders satisfactory results in around 60–70%. Haploidentical transplantation (HAPLO) offers a therapeutic alternative to more than 95% of such patients with the advantages of quick availability, easy programming and a committed donor. Patients and Methods: We evaluate the results of HAPLO with a reduced intensity conditioning regimen (Fludarabine 30 mg/m2 ×5 days (-6 to -2), Cyclophosphamide 14,5 mg/kg ×2 days (-6 and -5), IV Busulfan 3,2 mg/kg × 1–3 days (BUX, days -4 to -2) employing high doses of Cyclophosphamide post graft infussion (50 mg/kg days +3 and +4) as GVHD prophylaxis together with standard doses of cyclosporine and mycophenolate from day +5. Results: From Dec-2007, we have done 26 HAPLO in 4 spanish centers. Median age was 38 years (16–57), 20 were male and all were in advanced phases of their diseases (12 Hodgkin′s, 6 AML, 3 ALL, 2 MM, 1 MDS, 1 MF y 1 NHL). Previous autologous HSCT has been employed in 13 and allogeneic HSCT in 6 (2 MURD and 4 UCB). Disease status at HAPLO was CR in 8, PR in 14 and refractory in 4. Bone marrow was used in 16 and unmodified peripheral blood in 10. The haploidentical donor was patient′s mother (8), father (3), siblings (11) or other relatives (4). BUX was used in 1 dose (15), 2 doses (8) or 3 doses (2) and TBI 200 cGy in 1 case. Mean neutrophils engraftment was achieved on day +18 (13–26) and platelets >50K on day +27 (17–150) in all but 2 cases of graft failure (7.7%) due to progression (MF) or relapse (M7-AML). Main toxicities were grade 1–2 mucositis in 50%, febrile neutropenia in 75% and CMV reactivations in 58% with a 100 days NRM of 3.8% (1/26, VOD and MOF) and 10% NRM at 6 months (2/20). Grade II-IV acute GVHD appeared in 10/23 patients at risk (43%) and grade III-IV in 4/23 (17%). Chronic GVHD affected to 4/15 (27%), being extensive in 1/15 (6.7%). With a median follow-up of 9 months (1–38), 13/22 (59%) are alive in CR, progression or relapse has ocurred in 6/24 (25%). Immune reconstitution seems fast and complete in those evaluated. Conclusions: HAPLO with high-dose cyclophosphamide as GVHD prophylaxis is a useful alternative in the treatment of high risk hematologic tumours, with low toxicity, acceptable GVHD incidence and severity, long lasting remissions, and fast immunological reconstitution. Disclosures: No relevant conflicts of interest to declare.

Pretransplatation PET as Major Prognostic Discriminant in IGEV (ifosfamide, gemcitabine, vinorelbine and prednisone) Treated Patients with Relapsed/Refractory Hodgkin's Lymphoma (HL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3707-3707
Author(s):  
Rita Mazza ◽  
Stefano Luminari ◽  
Massimo Magagnoli ◽  
Michele Spina ◽  
Teodoro Chisesi ◽  
...  
Keyword(s):  
Complete Remission ◽  
Fdg Pet ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Response To Therapy ◽  
High Dose ◽  
Bulky Disease ◽  
The Impact

Abstract Abstract 3707 Poster Board III-643 Introduction response to salvage chemotherapy prior to high–dose therapy (HDT) is of major prognostic concern in relapsed/refractory HL. FDG-PET is able to distinguish between persistent disease and fibrosis/necrosis and has thus become the mainstay to define clinical response in this setting (Cheson et al, JCO 2007). The value of FDG-PET in this subset of patient is less well established. IGEV chemotherapy has shown very encouraging results as induction therapy in refractory/relapsed HL (Santoro et al, Haematologica 2007). Aims to retrospectively evaluate the predictive value of PET in pts with relapsed/refractory HL receiving IGEV and HDT. Methods seventy-two multicentric cases with refractory/relapsed HL who had completed IGEV x 4 courses and HDT between 01/98 and 05/07 were reviewed. FDG-PET evaluation was performed before HDT and, according to revised Cheson criteria, complete remission (CR) was defined as negative FDG-PET, independently from the presence of residual masses at CT scan. Univariate analysis was performed considering FDG-PET as well as other usually evaluated prognostic factors. Results patient characteristics: M/F 30/42, median age 33 (range 16-71), Nodular sclerosis 61 (85%), refractory 28 (39%), relapsed 44 (61%), one previous regimen 60 (83%), B symptoms 18 (25%), bulky disease 7 (10%), extranodal disease 32 (44%), previous radiotherapy 39 (54%). After induction, 36 pts (50%) received single (with BEAM as conditioning regimen ), and 36 (50%) tandem HDT (with melphalan as first and BEAM as second conditioning). After IGEV, on the basis of PET 47 pts (65%) were classified as complete remission (CR), 21 (29%) as partial remission (PR) and 4 (6%) did not respond. Ten of the 47 PET negative pts, and 18 of the 25 PET positive pts relapsed. With a median follow up 48 months, the 3-year PFS was 80% vs 25% for patient with negative vs positive PET respectively (HR 5.7 no CR vs CR - CI 95%: 2.6-12.4). The 3-year overall survival (OS) was 91% vs 56 % for patient with negative vs positive PET respectively (HR 7.8 no CR vs CR CI 95%: 2.6-23.7). In univariate analysis, factors influencing the probability of achieving CR to IGEV were disease status (refractory vs relapse) (p.096) and bulky disease at IGEV (p .088). Factor significantly associated with PFS and OS are reported in table. In multivariate analysis only response to therapy, as defined by pre-transplant PET result, maintained significance as prognostic indicator for both PFS (HR 5.7) and OS (HR 7.8). Conclusions these data in homogeneously treated pts with refractory/relapsed HL underline the crucial prognostic relevance of pre-transplant FDG-PET, even overwhelming the impact of disease status at progression. FDG-PET driven trials are highly recommended in this subset of patients. Disclosures: No relevant conflicts of interest to declare.

A Multivariate Clinical and Economic Model for Predicting Risk-Based Costs of Care for Acute Leukemia (AL) Patients (Pts) Undergoing Allogeneic Hematopoietic Cell Transplant (HCT)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3547-3547
Author(s):  
Joseph C. Alvarnas ◽  
Guido Marcucci ◽  
Ann Vanderplas ◽  
Eileen P. Smith ◽  
Joyce L. Murata-Collins ◽  
...  
Keyword(s):  
Advanced Disease ◽  
Performance Status ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Multivariable Analysis ◽  
Disease Status ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Clinical Risk ◽  
Care Costs

Abstract Background: Value is defined as health outcomes achieved per dollar spent. While risk-stratified AL HCT survival estimates are made possible by the Stem Cell Therapeutic Outcomes Database (SCTOD), an assessment of healthcare value is not possible as they do not include cost adjustments based upon clinical risk. We report a risk-based cost analysis, modeled on AL pts undergoing HCT at our institution that can potentially serve as a simple, statistically significant risk-based comparison tool. Methods: All AL pts who underwent HCT at City of Hope between 1/1/2010 and 12/31/2014 were included. Detailed data were captured from multiple electronic record sources in our database. Total direct costs were assessed for each pt from 14 days prior to 100 days post HCT. Categorical data were tested for associations by Chi-square; continuous data that were normally distributed were tested by T-test, while non-normal data were tested by Wilcoxon rank sum test. Univariate and multivariable logistic regression models were used to identify predictors associated with HCT costs ≥ median and ≥ 80th percentile. Univariate and multivariable Cox proportional hazards regression were used to identify predictors of overall survival (OS). All p-values were 2-sided with alpha level of 0.05. Results: This analysis included 389 pts (AML 352; ALL 37); median age was 52.5 years (yr) [range 1-74; 107 (27.5%) age ≥ 60]; 48% were female. At the time of HCT 204 (52%) were in 1st complete remission [CR], 87 (22%) in 1st relapse (rel)/2nd CR, and 98 (25%) >2nd CR/Induction Failure [IF]; ECOG performance status was ≥1 in 29.5% and Sorrer comorbidity score ≥1 in 56%. 214 (55%) and 175 (45%) received myeloablative (MAC) or reduced intensity (RIC) conditioning regimen, respectively; 231 (59%) had matched unrelated donor [MUD] or mismatched related donor (MRD) HCT. Graft-versus-host prophylactic (GVHD) regimen consisted of tacrolimus/sirolimus for 80% pts. 207 pts were enrolled on a therapeutic intervention trials and 121 had Medicare and/or Medicaid (Medi-Cal) as payer. Median follow-up was 12.9 months. The estimated 1- yr unadjusted OS for the entire group post-HCT was 71% (95% CI 66%-75%), 80% (74%-85%) for pts in 1st CR, 68% (57%-77%) for pts in 1st rel/2nd CR, and 56% (45%-65%) for pts >2nd CR/ IF. OS was similar for sibling matched and MUD/MRD transplants (1-yr OS 73% vs. 70%). In a multivariable analyses, disease status, MUD/MRD donor, MAC regimen, GVHD prophylaxis other than tacrolimus/sirolimus, ECOG ≥1, and Medicare and/or Medicaid as payer significantly predicted for cost ≥ median (Figure1A). Using Akaike Information Criterion (AIC) scores, donor type and disease status at HCT were found to be more informative variables with regard to higher cost of HCT. Disease status, MUD/MRD, MAC regimen, Medicare and/or Medicaid as payer and ECOG ≥1 also significantly predicted cost ≥ 80th percentile (Figure1B). In a multivariable analysis for OS (Figure 1C) , only >2nd CR/IF and HCT cost exceeding median had significantly higher hazard of death. Of note, despite reaching statistical significance in univariate analysis age, cytogenetics, treatment on protocol, and Sorrer score lost significance in adjusted higher costs and OS multivariable models. Conclusions: Our data suggest that: 1. Higher levels of care complexity drive higher costs, 2. Patients with more advanced disease status and inferior performance status have higher costs, 3. Statistically significant drivers of higher care costs are predictable prior to HCT. These risk factors are easily abstractable from medical records and provide prospective, equitably comparisons of risk-based costs between transplant centers. These data compliment the outcomes data available from the SCTOD and may enable providers and payers to make meaningful value comparisons between transplant centers. They may also help establish alternative models for payer contracting that include consideration of clinical risk-stratification. Of note, given the favorable survival outcomes of pts with higher cost-risk features (i.e., advanced disease status at HCT and MUD/MRD), the higher care costs associated with effective care of higher complexity pts are justified. While validation of this model is necessary using large payer or multi-institutional databases, we propose that similar clinical-economic models can be created for pts with other blood cancers requiring high complexity care. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures Forman: Mustang Therpapeutics: Other: Construct licensed by City of Hope.

Allogeneic hematopoietic cell transplantation for myelofibrosis (MF) in high risk patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7062-7062
Author(s):  
Swapna Narayana ◽  
Saurabh Chhabra ◽  
Ravi Kishore Narra ◽  
Aniko Szabo ◽  
Mehdi Hamadani ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Rank Test ◽  
Survival Outcomes ◽  
Unrelated Donor ◽  
Jak2 Mutation ◽  
Medical College ◽  
Kaplan Meier

7062 Background: Although allogeneic transplantation(alloHCT) is the only curative treatment modality for MF, given the median age of MF, most patients are not candidates for alloHCT due to concerns for treatment-related mortality(TRM), age and comorbidities. Methods: We reviewed the outcomes of 24 recipients of matched related/unrelated donor alloHCT for MF at the Medical College of Wisconsin. All patients with JAK2 mutation(62%) and/or constitutional symptoms recieved Roxulitinib atleast 4 months prior to alloHCT with discontinuation of Ruxolitinib 48 hrs prior to the start of conditioning. Majority(91%) received conditioning with Fludarabine and Busulfan(Flu/Bu4, Flu/Bu3,Flu/Bu4). Only 2 patients received TBI based regimen; Flu/TBI(2-4Gy). Those with splenomegaly > 22cm received pre-transplant splenic radiation(n = 11;49%). Survival outcomes were analyzed using Kaplan-Meier curves and compared between groups using log-rank test. Results: Median age was 57 years(range,40-67) with 29% > 60 years. A 46% had primary ET or PV that evolved to MF and 17% had MDS cytogenetics. Majority(74%) patients MF-3 grade. More than 80% recieved Ruxolitinib and 25% were treated with hypomethylating/cytotoxic chemotherapy. HCT-CI score was≥3 in 62%. Four patients had cirrhosis and portal hypertension(PHTN), and another 3 had PHTN without Cirrhosis.At median follow up of 36months, 3-year overall survival(OS) and relapse-free survival were(RFS) 70%. Marrow fibrosis improved post HCT with only 15% grade 3. One patient relapsed and died from AML 15 months post-HCT. TRM was 25% at 3 years; causes of death were sepsis(n = 3), alveolar hemorrhage(n = 1) and myocardial infarction(n = 1). Variables such as type of donor, DIPSS scoring, MF grade and age of the patient were not significantly associated with OS/RFS on univariate analysis. Conclusions: Despite advanced age and 62% with HCT CI≥3, we report excellent survival outcomes compared to other prior data. Careful patient selection, use of Ruxolitinib pre-HCT, splenic irradiation pre-HCT and Flu/Bu based conditioning regimen all contributed to the remarkable results in this series.

Allogeneic Hematopoietic Stem-Cell Transplantation After Nonmyeloablative Preparative Regimens: Impact of Pretransplantation and Posttransplantation Factors on Outcome

2001 ◽  
Vol 19 (14) ◽  
pp. 3340-3349 ◽  
Author(s):  
Mauricette Michallet ◽  
Karin Bilger ◽  
Frédéric Garban ◽  
Michel Attal ◽  
Anne Huyn ◽  
...  
Keyword(s):  
Disease Status ◽  
Allogeneic Transplantation ◽  
Initial Diagnosis ◽  
Myelogenous Leukemia ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Peripheral Blood Progenitor Cells ◽  
Conditioning Regimens ◽  
The Impact ◽  
Related Mortality

PURPOSE: To analyze the impact of pre- and posttransplantation factors on the outcome of allogeneic transplantation after nonmyeloablative conditioning regimens. PATIENTS AND METHODS: Ninety-two allogeneic transplantations after nonmyeloablative preparative regimens were reported to the Société Française de Greffe de Moelle Registry registry. Initial diagnoses were lymphoid diseases (n = 22), myeloma (n = 14), acute leukemia and myelodysplasia (n = 41), chronic myelogenous leukemia (n = 12), and solid tumors (n = 3). Forty-six patients had previously received a transplant, and 49 had progressive disease before transplantation. Three types of conditioning regimens were used with fludarabine or antithymocyte globulins. Eighty-nine patients underwent transplantation, 60 from peripheral-blood progenitor cells. Eighty-six patients received graft-versus-host disease (GHVD) prophylaxis for a median duration of 53 days. RESULTS: Seventy-nine patients engrafted, with 40 complete and 21 mixed chimerisms. The acute GHVD rate at 3 months was 50% ± 11%. Fifty-two patients achieved complete remission and 12, partial remission. At 18 months after transplantation, the overall survival (OS) and the transplant-related mortality (TRM) were 32% ± 12% and 38% ± 14%, respectively. Initial diagnosis and disease status before transplantation significantly influenced survival. Age and GHVD prophylaxis type significantly influenced TRM. We also showed an impact of GHVD prophylaxis duration on OS and TRM. In multivariate analysis, three factors remained of prognostic value on OS: initial diagnosis, disease status at transplantation, and GHVD prophylaxis duration. CONCLUSION: This series shows encouraging results from nonmyeloablative conditioning regimens before allotransplantation and demonstrates the impact of some pre- and posttransplantation factors on outcome after transplantation.

scholarly journals Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia

Blood ◽  
2006 ◽  
Vol 109 (5) ◽  
pp. 2256-2262 ◽  
Author(s):  
John E. Wagner ◽  
Mary Eapen ◽  
Margaret L. MacMillan ◽  
Richard E. Harris ◽  
Ricardo Pasquini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Fanconi Anemia ◽  
Marrow Transplantation ◽  
Survival Rates ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Donor Bone Marrow ◽  
The Impact

AbstractBone marrow transplantation (BMT) is the only known cure for the hematologic manifestations of Fanconi anemia (FA). Potential benefits of unrelated donor BMT for FA, however, have been severely limited by graft rejection and treatment-related mortality with resultant poor survival. Therefore, we evaluated the impact of potential prognostic factors on hematopoietic recovery, graft-versus-host disease (GVHD), and mortality in 98 recipients of unrelated donor BMT who received transplants between 1990 and 2003. Probabilities of neutrophil (89% vs 69%; P = .02) and platelet (74% vs 23%; P < .001) recovery were higher after fludarabine-containing regimens than nonfludarabine-containing regimens. Risks of acute GVHD (relative risk [RR], 4.29; P < .001) were higher with non–T-cell–depleted grafts. The day-100 mortality rate was significantly higher after nonfludarabine-containing regimens than fludarabine-containing regimens (65% vs 24%, respectively; P < .001). Corresponding 3-year adjusted overall survival rates were 13% versus 52% (P < .001). In addition, mortality was higher in recipients who were older (> 10 years), who were cytomegalovirus (CMV) seropositive, and who received more than 20 blood product transfusions before BMT. Based on these results, significant practice changes are suggested: use of a fludarabine-containing conditioning regimen in the context of T-cell–depleted marrow allografts, and earlier referral for transplantation prior to excessive transfusions in patients with marrow failure.

Second Autologous or Allogeneic Transplantation after the Failure of First Autograft in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3329-3329
Author(s):  
Muzaffar H. Qazilbash ◽  
Rima Saliba ◽  
Marcos de Lima ◽  
Daniel Couriel ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
Albumin Level ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Common Causes

Abstract Background: Most patients undergoing high-dose therapy and autologous transplant for multiple myeloma eventually relapse. The optimal salvage treatment for these patients is not very well defined. Both autologous and allogeneic hematopoietic stem cell transplantations have been used for salvage. We analyzed the outcomes of second autologous or allogeneic transplants, performed as salvage in patients relapsing after an autograft. Methods: Fourteen patients received a second autograft for salvage, while thirty-four patients underwent allogeneic transplantation (related 24, unrelated 10). The median age at transplant was 52 years in the autologous group, and 51 years in the allogeneic group. The median interval between the first and the second transplant was 25 months in the autologous group and 17 months in the allogeneic group. The disease characteristics were similar in both autologous and allogeneic groups. Results: With a median follow-up of 10 months among survivors in each group, both autologous and allogeneic transplant groups had a response rate (complete + partial) of 64%. One hundred day nonrelapse mortality was 7% in the autologous group and 12% in the allogeneic group. Median disease-free survival (DFS) was 11 months in the autologous and 6 months in the allogeneic group. Median overall survival (OS) was 29 moths in the autologous and 14 months in the allogeneic group. 1-year DFS was 40% in the autologous group and 22% in the allogeneic group (p = 0.2). 1-year overall survival was 70% in the autologous and 53% in the allogeneic group (p = 0.3). The most common causes of non-relapse mortality were graft vs. host disease (62%) in the allogeneic group, and infections (100%) in the autologous group. On univariate analysis for DFS in allogeneic group, an interval of >1 year between the first and the salvage transplant was the only factor associated with a significantly better outcome (p = 0.01). Disease status at transplant, type of donor, tumor mass, β2 microglobulin level, and serum albumin level did not show any impact on the outcome. Conclusions: Both autografting and allografting are feasible as salvage for myeloma patients relapsing after the first autograft. A slightly better outcome with salvage autografting may be due to decreased toxicity.

Platelet-Derived Microparticles Accelerate Engraftment of Peripheral Blood Stem Cells in Human Allogeneic Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3035-3035
Author(s):  
Christiane de Rop ◽  
Jan Priesack ◽  
Andreas Tiede ◽  
Arne Trummer
Keyword(s):  
Stem Cells ◽  
Cell Count ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Positive Control ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
The Impact

Abstract While the procoagulant activity of platelet derived microparticles (PMP) has been widely accepted, knowledge regarding their immunological and adhesive qualities is still limited. It has been shown that murine BM cells covered with PMP engrafted lethally irradiated mice significantly faster than those not covered, indicating that PMPs play an important role in the homing of peripheral blood stem cells (PBSC). Here we studied the impact of PMP on engraftment in human allogeneic PBSC transplants for patients with hematological malignancies. PBSC samples were collected in buffered citrate from transplantation bags after infusion of transplants into patients with hematological malignancies (AML = 5, ALL = 1). Conditioning regimens included busulfan/cyclophosphamide (Bu/Cy), anti-CD66b-radioimmunotherapy (RIT)/Bu/Cy, and reduced intensity regimens with fludarabin/busulfan (Flu/Bu) and FLAMSA. Platelet-poor plasma (PPP) was prepared (1500g for 20min), immediately shock-frozen in liquid nitrogen and stored at −80°C. For further analysis PPP’s were carefully thawed at room temperature (RT). 90μl of PPP was stained with 5μl of CD41-PE and CD62P-FITC each for 15min at RT in the dark (IgG1-FITC and -PE served as negative controls, TRAP-6 (10μM) stimulated whole blood processed in same way as samples as positive control). To stop staining 900μl PBS/BSA 2% was added and 500μl of this solution were transferred into BD Trucount tubes by reverse pipetting giving a final concentration of 100 beads/μl. Samples were analyzed immediately using Coulter FC500 flow cytometer with CXP software. As expected the CD34 cell count (mean=5.1x106/kg body weight, SD=2.0x106/kg) showed a significant correlation (p=0.0197, Pearson r=−0.83) with the time to engraftment (mean=15.7days, SD=2.0d). The amount of CD62P positive microparticles (mean=423/μl, SD=119/μl) and the conditioning regimen showed no significant correlation with CD34 cell count or time to engraftment with leucocytes >1000/μl. In contrast, CD41-PMP count (mean=1223/μl, SD=857μl) correlated significantly with the CD34 cell count (p=0.0086, Pearson r=0.92) and the time to engraftment (p=0.0039, Pearson r = −0.95). Therefore, PBSCT contain significant amounts of PMP which are most likely generated during apheresis. Preliminary results show a stronger correlation with time to engraftment than does CD34 cell count. We conclude that PMP may accelerate engraftment of PBSC in humans. However, this function seems unrelated to P-Selectin expression. Therefore, further studies aiming to identify other adhesion molecules involved in PMP-mediated engraftment of PBSCT are warranted.

No Improvement of Overall-Survival in Children with High-Risk Acute Myeloid Leukemia by Stem Cell Transplantation in 1st Complete Remission.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 320-320 ◽  
Author(s):  
Dirk Reinhardt ◽  
Bernhard Kremens ◽  
Martin Zimmermann ◽  
Josef Vormoor ◽  
Michael Dworzak ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Complete Remission ◽  
Children And Adolescents ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Hla Typing ◽  
Unrelated Donor ◽  
The Impact

Abstract One aim of the AML-BFM 98 study was to evaluate prospectively the impact of matched sibling donor (MSD)-SCT in 1st complete remission (CR) in children with high-risk (HR)-AML. Patients: Between 7/1998 and 3/2004 494 children and adolescents were enrolled in the studies AML-BFM 98 and the AML-BFM 98 Interim 2003. Patients with favorable cytogenetics [t(8;21), inv(16), t(15;17)], corresponding morphology (AML FAB M1/2 with Auer rods, M4eo, M3) and < 5% blasts on day 15 were defined as standard risk (SR)-group (n=177). All others were stratified to HR-group (n=317) and eligible for SCT in 1st CR. Out of 275 patients achieving 1st CR (87%) 63 patients had a MSD and 188 had no MSD (intent-to-treat group, ITT) while 24 patients had to be excluded due to missing HLA typing or initial refusal to SCT. Thirty-six patients received MSD-SCT (=as-treated group), another two children were transplanted from a matched unrelated donor (MUD) although an MSD was available. The reasons not performing SCT in 1st CR in the remaining 25 children with a donor available were early relapse (n=7), death in CR (n=2), clinical reasons (n=8), or refusal of SCT (n=8). Chemotherapy (CHT) only was given in 192 patients (n=167 without MSD, n=25 with a MSD). Another 21 children were transplanted from an unrelated donor (n=18), family donor (n=1), haploidentical donor (n=2). The reasons were slow response, very poor cytogenetics or other clinical reasons. Treatment: All patients received double induction and consolidation. MSD-SCT in 1st was scheduled after 4 blocs of treatment. Children who were not transplanted in 1st CR received intensification and a 1-year maintenance therapy. The recommended conditioning regimen consisted in busulfan and cyclophosphamide. Results ITT analysis revealed no significant differences in of 5 year disease-free survival (DFS) and overall survival (OS) between children with or without a donor (no donor vs. donor: DFS 43±4% vs. 47±7% plog rank 0.52; OS 56±4% vs. 58±9%, plog rank 0.16). The as-treated analysis gave similar results: CHT only vs. MSD-SCT: DFS 35±11% vs. 59±9% p Mantel-byar 0.13; OS 59±13% vs. 62±12%, p Mantel-byar 0.51). The major reasons of treatment failures were relapses in all groups [CHT only n=100 (52%), MSD-SCT n=13 (34%), MUD-SCT n=9 (50%)]. A 2nd CR was achieved in 71% of the CHT only group (n=74). After SCT in 2nd CR, OS was 40±6%. By contrast, only two children (9%) of 22 children after relapse following SCT in 1st CR could be salvaged. Severe late adverse events (e.g. severe chronic GvHD CTC grade IV, destruction of big joints, intracerebral bleedings) were more frequent in children transplanted in 1st CR (15%) than in those with CHT only (including SCT in 2nd CR; 5%, p×2< 0.05). Conclusion: In the population-based, prospective multi-center study AML-BFM 98 allogeneic MSD-SCT in 1st CR showed no advantage in children and adolescents with HR-AML. Considering the higher toxicity of allogeneic SCT, in the ongoing trial AML-BFM 2004, this SCT (MSD or MUD) is restricted to patients in 2nd CR and refractory AML.

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