Survival of AML Patients Relapsing after Hematopoetic Stem Cell Transplantation: A Single Center Experience

Abstract Although it is presumed to be a curative strategy for intermediate and high risk acute myeloid leukemia (AML), many patients relapse after allogeneic hematopoietic stem cell transplantation. This prompt us to examine the ways to improve the outcomes. We retrospectively evaluated 76 AML patients who were transplanted between 2007-2017 years in our clinic. We tried to identify the factors associated with posttransplant relapse, postrelapse survival and if there was a survival benefit of pretransplant consolidation and minimal residual disease (MRD) negativity. We examined the effect of the acute-chronic graft versus host disease (GVHD) and salvage therapy after the posttransplant relapses. The mean age of the patients was 44.6±1.21 years (ranges 21-67). 42.1% were females and 57.9% were males. 43.3% of the patients were in complete remission (CR) MRD positive state before the transplantation whereas 35.5% were in CR MRD negative and 3.9% were in progressive disease state. In 13 patients who were in CR state, the MRD status were not known. 11 (14.5%) patients were considered as in favorable risk, 52 (68.4%) in intermediate risk and 13 (17.1%) in unfavorable risk with respect to cytogenetic analysis before the transplantation. The donors were HLA compatible relatives (77.6%), HLA compatible non-relatives (10.5%), haploidentical people (9.2%), one HLA incompatible relative (1.3%) and one HLA incompatible nonrelative (1.3%). 74 bone marrow transplantations (97.4%) were allogeneic and the remaining two (2.6%) were autologous. Myeloablative conditioning regimen was applied to 57 patients (75%) and 19 patients got (25%) reduced intensity conditioning regimen. GVHD developed in 51.3% after transplantation and 61.5% of these were chronic extensive. Relapse occurred in 27 patients (35.5%), hematological relapse being the most common (31.6%). The median time for the development of relapse was found to be 5.5 months (range: 1.5-37). The overall probability for the development of a relapse was found to be 48.7% (95% CI: 40.9-56.5)(Figure1A). 23 patients (30.3%) died during the study period with a median survival of 9.6 months (range: 1.6-45). In the studied population the overall survival probability was found to be 52.8% (95% CI: 45.4 - 60.2) [Figure 1B]. 36.4%, 28.8% and 30.8% of the patients with favorable, intermediate and unfavorable cytogenetic status died respectively during the study period. The comparison of the survival probability of the patients with favorable, intermediate and unfavorable cytogenetic status was depicted in Figure 2. The overall survival probability of the patients with favorable, intermediate and unfavorable cytogenetic status were 46.6% (95% CI: 26.2-66.9), 54.6% (95 % CI: 45.9 - 63.2) and 36.9 % (95% CI: 25.4 - 48.5) respectively (p=0.807). MRD status of 60 patients were known. At the end of the study period 75.8% of the CR MRD positive and 70.4% of the CR MRD negative patients remained alive. The comparison of the survival of patients in CR with respect to MRD status is shown in Figure 3. The overall survival probability of CR MRD positive patients was 56.3 % (95% CI: 45.3 - 67.3) and this rate was 52.5 % (95% CI: 40.8 - 64.3) in MRD negative patients (p=0.770) [Figure 3]. Patients who developed GVHD had similar overall survival probability with the patients who did not developed the disease; 47.0% vs 57.2%, p=0.115 (Figure 4A). Even the patients with chronic extensive GVHD had similar overall survival rates with the patients who had none or acute GVHD; 49.3 % vs 58.2%, p=0.27 (Figure 4B). 66.7% of the patients with a progressive disease before the transplantation died during the study period and this rate was 27.1% in the patients with CR (p=0.005). In conclusion the overall survival rate of the transplanted AML patients was 52.8% in the study group. The overall survival did not seem to be affected by pre-transplant MRD status, cytogenetic risk factors and administration of consolidation therapy. The only patients who had significantly worse results were the ones who had progressive disease before the transplantation. From this point it would be logical to make transplantation whenever the patient is in first CR regardless of the MRD status and a matched donor is found so that the toxic effects of the consolidation chemotherapy may be prevented. Disclosures No relevant conflicts of interest to declare.

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Long-Term Clinical Outcome of Children with Acquired Aplastic Anemia in Brazil.

Blood ◽

10.1182/blood.v114.22.4216.4216 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4216-4216

Author(s):

Marlene Pereira Garanito ◽

Vicente Odone Filho ◽

Marcela Vieira dos Santos ◽

Elvira Velloso ◽

Frederico L. Dulley ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Aplastic Anemia ◽

Immunosuppressive Therapy ◽

Cell Transplantation ◽

Survival Probability ◽

Conflicts Of Interest ◽

Time History ◽

Hematopoietic Stem ◽

Significant Difference

Abstract Abstract 4216 Introdution/ Backgound Acquired Aplastic Anemia (AAA) is a rare hematologic disorder characterized by pancytopenia and hypocelular bone marrow. The pathophysiology is immune mediated in most cases. Environmental exposures to drugs, viruses and toxins, are thought to trigger the aberrant immune response in some patients. However, 50 to 74 percent of cases are classified as idiopathic. The highest frequency occurs in young population (15 to 25 years) with a second peak at age of 65 to 69 years. Immunosuppressive therapy is the best treatment in children with AAA who do not have a suitable donor for allogeneic stem cell transplantation. Materials and methods We reviewed the medical records of patients diagnosed with severe (SAA) and very severe acquired aplastic anemia (vSAA) at the Department of Pediatrics, Instituto da Criança – Hospital das Clínicas, University of Sào Paulo, Brazil from December, 1992 to December, 2007. We analyzed the clinical characteristics of the patients at diagnosis and the response to immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT). Results In this study, 47 patients (27 boys and 20 girls), younger than 16 years, were diagnosed with vSAA (n= 21) or SAA (n=26). The median age was 7,71 years, ranging from 0.5 to 16 years and the average time history (beginning of signs and symptoms related to the disease and diagnosis) of the disease was 4,82 months, ranging from 0,25 to 48 months. Of the 47 patients, 45 had idiopathic AAA and 2 had hepatitis-associated. The median follow-up was 6,91 years for the patients treated with IST and 3,10 years for the patients who underwent to HSCT. One patient died before any treatment. For the eight patients who underwent to allogenic HLA-matched HSCT the 5-years-survival probability was 50%. For the 38 patients treated with IST, ten of them received cyclosporine and a short course of corticosteroids (CsA/CE) and 28 received antithymocyte globulin plus cyclosporine (ATG/CSA). The 5 years survival probability was 40% and 55%, respectively (p:0,0054). According to the severity of AAA, we did not show a significant difference in survival (p:0,32). Eight patients received second treatment after 1 year and 6 months (6 ATG from different species and CsA, 1 CsA and 1 thalidomide) and the probably of survival at 5 years was 60%. Among the 18 patients who responded to IST, four relapsed (22%). Two patients developed acute myeloid leukemia at 5 and 12 years after diagnosis. Conclusion Our results both for patients undergoing HSCT, as well as patients undergoing IST are lower in comparison to other hematological centers. Probably, this discrepancy is related to the prolonged time of disease when patients are admitted to our service. Unfortunately, the difficulty of access to specialized centers for diagnosis and early treatment in our country is a reality and this fact contributes to the delay to the beginning of treatment. Disclosures: No relevant conflicts of interest to declare.

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Femoral Head Necrosis In Three Patients After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v122.21.5489.5489 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5489-5489

Author(s):

Gang Zhao ◽

Zhi Li ◽

Jiahua Ding ◽

Jun Wang ◽

Zhengping Yu ◽

...

Keyword(s):

Stem Cell ◽

Femoral Head ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Femoral Head Necrosis ◽

Hematopoietic Stem

Abstract Femoral head necrosis (FHN) is one of common complications after hematopoietic stem cell transplantation (HSCT). It impacts on patients' normal life with severe pain. To investigate FHN after allogeneic HSCT, We performed retrospective analyses. Since 2003, our department has conducted 98 cases of allogeneic hematopoietic stem cell transplantation for patients with hematologic diseases. Chemotherapy regimens and transplant conditioning regimen before transplantation were steroid-free. FHN occurred in 3 out of 98 cases. The 3 patients were treated with steroid for preventing graft versus host disease (GVHD) after transplantation. However, all the three patients suffered from GVHD, which was cured with steroidal medication subsequently. Then, symptoms of FHN come out and were significantly improved after conservative treatment in all the three patients. The occurrence of FHN might be associated with GVHD and corticosteroids prescription. Early prevention might be helpful in reducing the incidence and improving outcomes. Disclosures: No relevant conflicts of interest to declare.

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Monosomal Karyotype in Myeloid Malignancies Is Prognostically Worse Even After Allogeneic Hematopoietc Stem Cell Transplantaion; Results From Two Transplant Centers,

Blood ◽

10.1182/blood.v118.21.4154.4154 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4154-4154 ◽

Cited By ~ 1

Author(s):

Minauchi Koichiro ◽

Akio Shigematsu ◽

Masanobu Nakata ◽

Toshihiro Matsukawa ◽

Koh Ebata ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Cox Regression ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Structural Abnormality ◽

Hematopoietic Stem ◽

Myeloid Malignancies ◽

Monosomal Karyotype

Abstract Abstract 4154 Background: Monosomal karyotype (MK) has been defined as the presence of two or more autosomal monosomies or of a single monosomy associated with at least one structural abnormality (Breems et al, JCO 2008). The presence of MK has been associated with extremely poor prognosis in patients with not only acute myeloid leukemia (AML) but myelodysplastic syndrome (MDS) (Patnaik et al, Leukemia 2011). Our goal was to investigate the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for myeloid malignancies with MK. Patients and methods: We combined data from two transplant centers, Sapporo Hokuyu Hospital and Hokkaido University Hospital, and analyzed consecutive patients who underwent allogeneic transplantation for AML and MDS between January 2003 and July 2010. Patients were divided according to MK classification scheme into four groups (Oran et al, BBMT 2011), CN; cytogenetically normal, MK; monosomal karyotype, CBF; core binding factor abnormalities, Oth (Others); non-CBF and non-MK abnormalities. Patients with acute promyelocytic leukemia were excluded. Resuts: One-hundred eighty three out of 229 patients were analyzed with a median age of 48 years(15–68). Sixty one (33%) were from HLA-matched related donors, 86 (47%) from unrelated and 36 (20%) were cord blood.Conditioning regimens were myeloablative (MAC, n=102, 56%) or reduced intensity(RIC, n=81, 44%). Seventy patients (38%) were cytogenetically normal, 27 (15%)had CBF abnormalities, 70(38%) had non-CBF and non-MK abnormalities and 16(9%) had monosomal karyotype. There was no statistically difference between four groups in age, donor source and conditioning regimen. In the MK group, the proportion of MDS and non-remission state at stem cell transplantation were significantly higher than other groups (p=0.002, p<0.001). Four-year over all survival in patients with MK was 0%, which was significantly inferior to other groups; 50% for CN, 30.4% for CBF, 29.4% for Oth(p<0.001). Cox regression modeling showed that the disease status at stem cell transplantation (p=0.026) and the existence of MK (p=0.012) had prognostic value. Seven of 16 patients with MK died within the first 50 days after transplantation, and 9 patients died within 120 days. Five patients died of infection and 2 died of complicated organ failure and 2 died of progression disease. Three patients who underwent transplantation at non-remission setting, survived more than 1-year experienced chronic graft-versus-host disease, suggesting the existence of GVL effect to myeloid malignancies with MK. Conclusion: This retrospective analysis revealed the dismal prognosis of myeloid malignancies with MK, even after allogeneic HSCT. Novel therapies and strategies are urgently needed for this very poor prognostic group. Disclosures: No relevant conflicts of interest to declare.

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Cost Analysis Of Stem Cell Transplantation In Developing Countries: Experience Of a Single Public Center In Mexico

Blood ◽

10.1182/blood.v122.21.1733.1733 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1733-1733 ◽

Cited By ~ 1

Author(s):

Eucario León-Rodríguez ◽

Patricia Guzmán-Uribe ◽

Sandra Ileana Pérez-Álvarez ◽

Isabel Cortina-Pastor

Keyword(s):

Overall Survival ◽

Developing Countries ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Conflicts Of Interest ◽

Tertiary Care ◽

Blood Bank ◽

Median Cost ◽

Hematopoietic Stem

Abstract Introduction Hematopoietic stem cell transplantation (HSCT) has become an important strategy for treatment of several diseases. However, in developing countries access is often limited by socioeconomic factors. The information about the costs of the procedure in Mexico is scarce which limits the development of public policies in the area. Objective Describe overall costs of HSCT as well as specific costs of resources used in a tertiary care center in Mexico City. Material and Methods Retrospective, descriptive, observational study. We calculated the median overall cost per transplant in the first 30 days and the median cost per resource category, using SPSS version 17. Results We evaluated a total of 50 TCPH from June 2010 to December 2012. Of all the procedures, 68% were autologous. The median cost for allo-HSCT was $ 24.910 USD, while for auto-HSCT was $14.742 USD. Specific charges were divided into the following areas: for allo-HSCT, conditioning chemotherapy and mobilization: $ 4.087 USD, hospitalization: $ 8.130 USD, laboratory studies: $ 3.922 USD, imaging: $ 1.012 USD, other medications: $ 5.278 USD, blood bank: $ 2.478 USD. For auto-HSCT, conditioning-mobilization: $ 4.997 USD, hospitalization $ 4.086 USD, laboratory $ 1.612 USD, imaging: $ 411 USD, other medications: $ 3.024 USD, blood bank: $ 611 USD. Estimated 5 year-overall survival for these patients was 71.6%. Conclusions These results contribute to the scarce information regarding costs of HSCT in our country. The cost of HSCT in INCMNSZ (government institution) is 10 times lower than in the U.S. with similar results regarding overall survival. These facts highlight the important role of non-profit institutions that contribute to the development of these programs. Disclosures: No relevant conflicts of interest to declare.

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Allogeneic Stem Cell Transplantation - A Long-Term Curative Approach In Patients ≥ 60 Years With Advanced Disease AML/MDS, - The Freiburg Experience Of 250 Consecutive Patients

Blood ◽

10.1182/blood.v122.21.2135.2135 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2135-2135

Author(s):

Hartmut Bertz ◽

Michael Lübbert ◽

Kristin Ohneberg ◽

Ralph Wäsch ◽

Robert Zeiser ◽

...

Keyword(s):

Stem Cell ◽

Prognostic Factors ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Advanced Disease ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Hematopoietic Stem

Abstract Since the introduction of reduced-toxicity conditioning prior to allogeneic hematopoietic stem cell transplantation (alloSCT) we transplanted from 1999 to 2012, 250 consecutive patients (pts) with myeloid malignancies (AML, MDS) aged ≥ 60 years (yrs). The 144 male and 106 female pts with a median age of 66 yrs (range 60-77) were transplanted for de novo AML (n=95), s/tAML (n=104) and MDS (n=51) with 89% unfavorable cytogenetics (CALGB). Since 2004 pts received a prospective fitness assessment (Deschler et al., Haematologica 2013). In 74% the donor was matched/mismatched unrelated and in 26% related. Only 16% were transplanted in CR1/2, 84 % with advanced or untreated disease. The conditioning regimen was the FBM protocol (fludarabine, carmustine, melphalan; Bertz et al., JCO 2003) in 98%, and 97% of the pts received PBSC. For GVHD prophylaxis in 91% a combination of cyclosporine plus alemtuzumab or ATG-F™ was used. At day +30, 94% of the pts had achieved CR by standard measures. With a median follow up of 57 months (3-157) 37% of the pts are alive; main causes of death were relapse (n=62), infection (n=35) and age-related diseases (n=13). The probability of OS/DFS was at 1yr 61%/49%, at 2 yrs 49%/41% and at 5 yrs 37%/34%, respectively. The probability for NRM at 1 yr is 24%. Nineteen known prognostic factors for outcome were evaluated: e.g. patient and donor age, graft size, days between diagnosis and alloHCT, CMV, early/advanced disease, cytogenetics, Sorror and Gratwohl score, donor type, HLA-identity. In the multivariate analysis a better OS (factors with p<0.1; table) was seen with a matched donor; a better DFS with a related donor, and high CD34+ graft content; in contrast, a mismatched donor is a risk factor for reduced DFS.TableMultivariate analysis of prognostic factors* for OS and DFSvariablevalueHazard Ratio95% CI lower limit95% CI upper limitP valueOverall survivalRemission at alloHCTadvanced1.370.862.160.1825HLA mismatchyes1.401.011.960.0463HCT-CI (Sorror)>= 21.311.011.960.1007Peripheral blood blastsyes1.210.841.760.3034Disease-free survivalRemission at alloHCTadvanced1.290.722.300.3946Donorrelated0.640.430.950.0258HLA mismatchyes1.440.992.090.0561CD34+ cells> median0.760.551.040.0867Bone marrow blasts> 5%1.210.781.880.3915*in univariate analysis p<0.157 (AIC criterion; Sauerbrei W, 1999 Applied Statistics,48:313-329.70.) In conclusion, this unique large cohort of older pts with AML/MDS with mainly advanced disease and unfavorable cytogenetics shows a high feasibility, safety and efficacy of alloHCT after the FBM protocol. AML/MDS pts in their 7th and 8th decade of life fit for transplant should be evaluated for alloHCT as very important long-term curative option. Disclosures: No relevant conflicts of interest to declare.

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Effect of Melphalan 140 Mg/m2 Versus 200 Mg/m2 on Toxicities and Outcomes in Multiple Myeloma Patients Undergoing Single Autologous Stem Cell Transplantation

Blood ◽

10.1182/blood.v126.23.1988.1988 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1988-1988

Author(s):

Lakshmikanth Katragadda ◽

Lindsay McCullough ◽

Yunfeng Dai ◽

Jack W Hsu ◽

John W Hiemenz ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Disease Status ◽

Cox Proportional Hazards Model ◽

Hematopoietic Stem ◽

Preparative Regimen

Abstract Introduction: Although melphalan at a dose of 140 mg/m2 (MEL-140) is known to be an effective preparative regimen for autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) patients, there are very few studies comparing it to the most commonly used dose of 200 mg/m2 ( MEL-200). Methods: We retrospectively reviewed the records of all myeloma patients who underwent an ASCT between 2001 and 2010 at our institution. We then identified patients who received melphalan as their preparative regimen at doses of 140 mg/m2 or 200 mg/m2. Patients who received any other drug as conditioning regimen or had more than one ASCT or had documented amyloidosis were excluded. Data were collected for variables known to possibly affect prognosis of MM patients. We assessed effect of melphalan dose on toxicities and outcomes. Results: A total of 129 eligible patients were identified, with 33 receiving MEL-140 and 96 receiving MEL-200. As was expected significantly higher percentage of patients in the MEL-140 arm were older than 65 years (P=<0.001) or had cardiac ejection fraction < 50 (P=0.0001) or had Karnofsky score < 80 (P=0.01) or had creatinine > 2 either at diagnosis (P=0.004) or the time of ASCT (P=0.001). Rest of the patient and disease characteristics including Durie-Salmon stage, myeloma subtype and disease status at ASCT were not significantly different between the 2 arms. Patients in MEL-140 needed significantly longer time to ANC engraftment (P=0.037) and also had significantly higher frequency of neutropenic fever (P=0.003). There were no significant differences in mucositis (including grade), nausea, vomiting, diarrhea, bacteremia, or length of hospital stay and frequency of repeat hospitalizations among both groups. There was no treatment related mortality in either group. At a median follow up of 74 months (range, 52-140) from ASCT, there were no significant differences in relapse free survival (RFS) (P=0.4988) and overall survival (OS) (P=0.6936) between the two groups. Five year OS for MEL-140 and MEL-200 is 71.6% and 78.9%, while RFS is 23.9% and 34%, respectively. Proportion of patients whose myeloma status improved to ≥ VGPR at 3 months post ASCT was also not different (P=0.385). Importantly, similar proportions of patients received various post ASCT maintenance therapy (P=0.605). In multivariate cox proportional hazards model only disease status of ≥VGPR at the time of ASCT significantly affected RFS (P=0.024) but did not impact OS (P=0.104). Conclusion: MM patients who received MEL-140 had similar long term outcomes as those who received MEL-200 despite their older age, lower performance status and renal insufficiency. Disclosures No relevant conflicts of interest to declare.

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Haploidentical Stem Cell Transplantation for Rare Pediatric Diseases at Peking University People's Hospital

Blood ◽

10.1182/blood.v128.22.5848.5848 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5848-5848

Author(s):

Yao Chen ◽

Huan Chen ◽

Lan-Ping Xu ◽

Yu-Hong Chen ◽

Jing-Zhi Wang ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Disease Patient ◽

Rare Disorders ◽

Hematopoietic Stem ◽

Pediatric Diseases ◽

Conditioning Regimens

Abstract Background:Rare diseases requiring hematopoietic stem cell transplantation (SCT) present a challenge for BMT centers. The patients present at a low frequency, and there are often no established conditioning regimens for these disorders, especially for children without HLA matched sibling donors. We report the conditioning regimen using haploidentical related donors, and outcomes for the following rare disorders transplanted at our center from January 2013 through December 2015. During the past three years we had patients presented with the following: Fanconi anemia (FA), dyskeratosis congenital (DC), adrenal leukodystrophy (ALD) and Wiskott-Aldrich syndrome (WAS). Methods:We treated these children with rare disorders that required SCT at our center, and are reporting the transplant outcomes for these rare diseases. Results: All children were transplanted with haploidentical related donors using G-CSF mobilized bone marrow and peripheral blood stem cell. Conditioning regimens and treatment plans were mainly following Beijing protocol and varied with type of disease. Patient characteristics and outcomes are presented in Table 1. No graft failure occurred and three of 5 patients (60%) are alive and well with no evidence of disease. Conclusions: Our program has treated a variety of rare disorders with an event-free-survival rate of 60%. Our data suggests haploidentical SCT for rare pediatric diseases seems to be challenging and promising. Disclosures No relevant conflicts of interest to declare.

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Impact of Conditionning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Children with Acute Myeloid Leukemia in First Complete Remission: Total-Body Irradiation and Cyclophosphamide Versus Busulfan and Cyclophosphamide - A Report from The Societe Francaise de Greffe de Moelle et de Therapie Cellulaire.

Blood ◽

10.1182/blood.v110.11.617.617 ◽

2007 ◽

Vol 110 (11) ◽

pp. 617-617 ◽

Cited By ~ 1

Author(s):

Jean-Hugues Dalle ◽

Luc Caty ◽

Regis Peffault ◽

Alexandra Salmon ◽

Valerie Mialou ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Cumulative Incidence ◽

Conditioning Regimen ◽

Unrelated Donor ◽

Matched Unrelated Donor ◽

Hematopoietic Stem

Abstract Goal: Compare results after allogeneic HSCT for AML in CR1 in pediatric population after myeloablative conditioning regimen either based on TBI or busulfan. Patients and Methods: Retrospective analysis from French registry including all consecutive patients under 18 years of age (n=131) from Dec’1979 and Oct’2004 transplanted for AML in CR1 with either sibling (n=104) or matched unrelated donor and given either multi-fractionated TBI 12Gy and cyclophosphamide 120mg/kg (TBI-Cy) or Busulfan 16mg/kg and Cyclophosphamide 200mg/kg (BuCy200). Results were analysed according to EBMT statistical analysis guidelines i.e. OS and EFS were analyzed by KM method and Log-rank test for comparison where TRM and relapse incidence were analyzed by cumulative incidence method and Gray test for comparison. Multivariate analyses were performed using proportional hazard model for the distribution of competitive risks defined by Fine and Gray. Results: 131 patients (female: 51.5%) were included. Median age at initial diagnosis was 11y (0.5 to 17.8). Median time from diagnosis to transplantation was 4.2 months. Eighty-three patients received BuCy200 and 48 patients were transplanted after TBI-Cy. Patient subgroups were comparable for age, gender, sex mismatch, source of graft (BMT vs PBSC), donor type (geno-identical vs 10/10 matched unrelated donor vs other), cytogenetical analysis and WBC at initial diagnosis, and for donor-recipient CMV status (−/+ vs others). Both 5 year-overall and event-free survival rates appeared significantly better in BuCy200 group than in TBI-Cy group with 73.3% vs 56.1% (p=0.02) and 67+/−7% vs 38+/−9% (p=0.002), respectively. TRM incidence at day 365 was dramatically better in BuCy200 group than in TBI-Cy group with 4,7% vs 26.1% of TRM rate (p=0.002), respectively. Even though there were no statistical significant differences for both acute and chronic GVHD cumulative incidences whatever given conditioning regimen, there was a trend for obtaining lesser GVHD in BuCy200 group: day 100 grade II-IV aGVHD cumulative incidence was 13% vs 37% and 2 year extensive cGVHD was 9 vs 19% for BuCy200 and TBI-Cy group, respectively. At 5 years, there was a trend for less relapse in BuCy200 group than in TBI-Cy 16+/−3% vs 32+/−6% (p=0.09), respectively. Conclusion: This study demonstrates the superiority of BuCy200 on TBI-Cy conditioning regimen for paediatric patients presenting with AML in CR1 and undergoing allogeneic hematopoietic stem cell transplantation from either matched related or unrelated donor. These results, obtained from a larger cohort, confirm and update those published by our group in 1994. Figure 1: Overall survival Figure 1:. Overall survival

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Anti-CD25 instead of ATG for the Conditioning of HLA-Mismtched Hematopoietic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v114.22.4315.4315 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4315-4315

Author(s):

Jun Wang ◽

Qingxiang Meng ◽

Nailan Guo

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Hla Typing ◽

Peripheral Blood Stem Cells ◽

Hematopoietic Stem

Abstract Abstract 4315 Purpose To analysis the effect of Anti-CD25 instead of ATG for the conditioning of HLA-mismatched hematopoietic stem cell transplantation (HSCT). Methods 21 cases underwent HLA-mismatched HSCT in our hospital from Mar. 2006 to May 2009. Diagnosis included ANLL(n=9)(2 in CR,7 in Relapse)?ALL(n=2), AHL(n=2), CML(n=4), MDS (n=2) and SAA (n=1), HLA Typing : All patients receive transplants from HLA-mismatched related donors. Among whom, 1,2 and 3 antigen mismatched were 11,8 and 2 cases respectively. Conditioning regimen consisted of modified BU/CY (n=12), BU/CY (n=6), FLU/BU (n=2) and CY/ATG for SAA(n=1). In addition, ATG(Thymoglobuline, 5-7.5mg/Kg, iv, divided into three days, -8∼-6d) was given for 8 patients. Anti-CD25 was given for 13 patients, including Daclizumab (50mg/d, -1?,03?,+4?,+11d) for 7 patients and Basiliximab (20mg/d, -1?,02?,+2?,+7d) for 6 patients. GVHD prophylaxis consisted of CSA and short course of MTX. In addition, MMF was given in all patients at the dosage 1.0 g/d for one month. The donors were given granulocyte colony-stimulating factor (G-CSF) at a dosage of 5 μg/Kg.d subcutaneously for 5 days, bone marrow was collected on day 3, peripheral blood stem cells were collected at day 4 and 5. Results Engraftment was obtained in all 21 patients, the median time to WBC >0.5×109/L and BPC>20×109/L in ATG and Anti-CD25 group were 14, 13d and 13, 12d, respectively (p>0.05), I∼II aGVHD accurred in 3 cases(37.5%) in ATG group and 5 cases(23.1%) in Anti-CD25 group,III∼IV aGVHD was observed in 1 case (12.5%) in ATG group and 2 cases (15.3%) in Anti-CD25 group. cGVHD was evaluable in 14 patients who survived after day +100, Extensive cGVHD developed in 1 (20%) of 5 patients in ATG group, and in 4 (44%) of 9 patients in Anti-CD25 group. Daclizumab and Basiliximab were not cause any infusion-related toxicity. Up to now, 13 patients survived in complete remission follow up 3-59 months, 4 cases (50%) died (3 in TRM and 1 in relapse) in ATG group, 4 cases (30.7%) died (1 in TRM and 3 in relapse) in Anti-CD25 group. Conclusion The replacement of ATG with Anti-CD25 seems to be more safety and effective for the conditioning of HLA –mismatched HSCT. Disclosures: No relevant conflicts of interest to declare.

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Feasibility of Hematopoietic Stem Cell Collection and Cryopreservation in Waldenstrom's Macroglobulinemia

Blood ◽

10.1182/blood.v120.21.4128.4128 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4128-4128

Author(s):

Dilshad Khan ◽

Krina Patel ◽

Sheeba K. Thomas ◽

Donna M. Weber ◽

Kay B Delasalle ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Growth Factors ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Conflicts Of Interest ◽

Cancer Center ◽

Hematopoietic Stem ◽

Number Of Patients ◽

Cd34 Cells

Abstract Abstract 4128 Background: Although autologous stem-cell transplantation (auto-HCT) is sporadically used in patients with Waldenström macroglobulinemia (WM), hematopoietic stem cells (HSC) are routinely collected and cryopreserved at many transplant centers after initial cytoreduction, prior to the use of myelotoxic agents like cladribine. The aim of this study is to evaluate the number of patients who underwent HSC collection, the adequacy of collection and the number of patients who eventually received auto-HCT. Methods: We performed a retrospective chart review for 431 adult patients with WM who were seen at the University Of Texas-MD Anderson Cancer Center (MDACC). Fifty-five patients (12.8%) underwent HSC collection. Our analyses were focused on these 55 patients. Results: A total of 431 patients with WM were seen at our institution between 1978 and 2010. One-hundred and seven (24.8%) of these patients were referred to the Department of Stem cell Transplantation (SCT). Fifty-two patients either continued conventional therapy (31) or received plasmapheresis for hyperviscosity (21). Fifty-five (12.8%) patients underwent HSC collection either through peripheral blood (PB) HSC mobilization or bone marrow (BM) harvest. Characteristics of the 55 patients undergoing HSC collection are summarized Table 1. In 2 patients, HSC were collected by BM harvest only. Fifty-three patients underwent PB HSC mobilization with either growth factors only (34) that included filgrastim, pegfilgrastim or plerixafor; or with growth factors plus chemotherapy (19) that included cyclophosphamide alone or in combination with vincristine, doxorubicin and dexamethasone (CVAD). Out of 53 patients undergoing PBHSC mobilization, 2 patients failed to mobilize any HSC despite growth factors and chemotherapy, while 2 additional patients had inadequate HSC collection (< 2 × 10e6 CD34+ cells/kg). Forty-nine of the 53 patients undergoing PBHSC mobilization had adequate HSC collection (> 2 × 10e6 CD34 cells/kg). Overall, 51 patients (PBHSC: 49, BM harvest: 2, 93%) had an adequate (> 2 × 10e 6 CD34/kg) HSC collection. The median HSC dose collected from these patients was 6.9 × 10e6/kg ((0.5–24.1) after a median of 3 collections (1 to 7). Fifteen patients had received cladribine prior to HSC collection, and 14 (93%) of them had adequate HSC collection. However, 7/15 patients (47%) with prior cladribine required chemomobilization, in contrast to 11/39 (28%) without prior cladribine (p=0.21). In 34/51 patients with adequate collection, HSC were cryopreserved for use at the time of relapse. Thus far, 3/34 (8.8%) have gone on to receive auto-HCT after 12, 27.3 and 45.2 months, respectively. In 31/34 (91%) patients, HSC have been cryopreserved for a median duration of 24.6 months (3.1 to 187.6 months). In 17 patients, HSC were collected with the intention to immediately proceed to auto-HCT, and these patients proceeded to HDM and auto-HCT within 3 months of HSC collection (range being 0.1–2.7 months). Forty-four patients are alive after a median of 37.5 months (2.4 to 187.6) from HSC collection. Kaplan-Meier estimate of 5-year overall survival for all patients from HSC collection was 76%. Conclusions: Current frontline regimens for WM are associated with high overall response rates (66–94%); however, complete remission (CR) rates (4–7%) remain low. Given the feasibility of HSC collection in patients with WM, earlier incorporation of auto-HCT for younger patients could be studied as a means of improving CR rates, and perhaps thereby improving both remission duration and overall survival. Disclosures: No relevant conflicts of interest to declare.

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