Relevance and Factors Predicting for Early Lymphocyte Recovery After Allogeneic Bone Marrow Stem Cell Transplantation (BMT).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3053-3053
Author(s):  
Ulas D. Bayraktar ◽  
Rima M Saliba ◽  
Gabriela Rondon ◽  
Antonio Di Stasi ◽  
Partow Kebriaei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Proportional Hazards ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Allogeneic Bone ◽  
Limited Information ◽  
Grade Ii

Abstract Abstract 3053 Recovery of the immune system is critical for the success of allogeneic stem cell transplantation. Several groups, including ours, reported that faster lymphocyte recovery was associated with improved outcomes. There is limited information however, on factors affecting lymphocyte recovery and its influence on outcomes specifically after BMT. We retrospectively assessed 536 consecutive patients (pts) with acute leukemia (452 AML/MDS and 102 ALL) who underwent BMT (and engrafted) at our institution between 01/1999 and 12/2010 to determine 1) predictors of early lymphocyte recovery (ELR), and 2) influence on outcomes of ELR defined as achieving absolute lymphocyte count of 1000/μL (ALC1000) by day 100 after BMT. Characteristics of the study population including demographics, graft, disease, and transplant characteristics assessed are described in the Table. Conditioning regimens were classified as reduced intensity (RI), or high intensity (including TBI-, busulfan-, or melphalan-based) conditioning, as previously described. Cox's proportional hazards regression analysis was used to assess predictors of ELR and NRM on univariate and multivariate (MV) analysis. Pts who developed grade II-IV acute GVHD (aGVHD), received a second graft infusion, or relapsed before achieving ALC1000 were censored at the time of these events for the assessment of predictors of ELR. Only pts who were alive progression-free, and had not developed grade II-IV aGVHD by day 100 were eligible for the assessment of predictors of outcomes in landmark analysis starting on day 100 after BMT. Outcomes were assessed at the median follow-up in surviving pts of 40 months. On multivariate analysis, significant predictors of lower rate of ELR included TBI- or melphalan-based ablative conditioning (HR=0.5, p 0.003) (compared to RI or busulfan-based), and a haploidentical donor (HR=0.4, p 0.05). Preliminary analyses assessing CMV reactivation and grade II-IV aGVHD as time dependent variables showed these factors to be associated with higher and lower ELR, respectively. MV analyses incorporating these factors in prognostic model are ongoing and final results will be presented at the meeting. Among the 246 pts eligible for the outcomes assessment, ELR (HR=0.2, P <0.001) and remission status (CR1/CR2) at transplant (HR=0.3, P 0.004) were the only significant predictors of the rate of NRM on MV. The lower NRM rate in pts with ELR translated into higher overall survival on univariate analysis, yet this association was only significant at 1 year (HR1year 0.5, p=0.02; HR40 mo 0.7, p=0.2) after transplant. There was no impact for ELR on the rate of disease relapse at either one of these time points after BMT. In conclusion, early lymphocyte recovery is an independent prognostic factor for NRM after BMT. Lymphocyte recovery was influenced by the conditioning regimen, the use of a haploidentical donor and the development of aGVHD but not by the infused CD34 cell numbers or disease status at transplant. Disclosures: No relevant conflicts of interest to declare.

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 ◽  
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.

Allogeneic Stem Cell Transplantation from Unrelated Donors after Reduced Intensity Conditioning in Patients with MDS/sAML. A Report from the Chronic Leukemia Working Party (CLWP) of the EBMT.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5176-5176 ◽  
Author(s):  
Nicolaus Kroeger ◽  
Ronald Brand ◽  
Rodrigo Martino ◽  
Philippe Guardiola ◽  
Anja van Biezen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Working Party ◽  
Stem Cell Source ◽  
Unrelated Donors

Abstract We analysed the results of 67 patients with MDS/sAML who were transplanted with allogeneic stem cell transplantation from unrelated donors after a reduced intenisity conditioning and reported to the EBMT. The median age was 52 years (range 17–70 years) and stem cell source was bone marrow (n = 30) or peripheral blood progenitor cells (n = 33).. The graft was HLA matched in 57 patients while 8 patients received SCT from HLA-mismatched donor. The MDS classification was as follows: RA/RARS: n=8, RAEB/CMML: n = 14, RAEB-t/sAML: n = 22. The conditioning regimen consisted of fludarabine/busulfan (n=15), fludarabine/melphalan (n=6), fludarabine and TBI (n=8) or fludarabine and others (n=36)At time of transplantation only 12 (18%) were in first complete remission. The Kaplan-Meier estimates of the probability of 2 years overall and disease free survival were 33 % (95% CI: 21–45 %) and 24 % (95% CI: 12–36 %), respectively. The probability of relapse at two years was 58 % (95% CI: 40–76 %) and of one year treatment-related mortality 37 % (95% CI %: 23–51 %). In an univariate analysis assessing source of stem cells, age, disease type, T-cell depletion, and HLA-matching no factor was significant for OS, EFS, TRM and Relapse. Allogeneic stem cell transplantation after a reduced intensified conditioning followed by unrelated SCT seems to be a feasible approach in those patients who were no candidates for a standard conditioning but is associated with a considerable number of relapses.

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.

Is There a Role for Autologous Stem Cell Transplantation (Auto SCT) for Patients with Acute Myelogenous Leukaemia? A Retrospective Analysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1689-1689
Author(s):  
Nicolas Novitzky ◽  
Valda Thomas ◽  
Cecile du Toit ◽  
Andrew McDonald
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Entire Group ◽  
Myeloablative Conditioning ◽  
Post Transplant ◽  
Significant Difference

Abstract Abstract 1689 Introduction: To better counsel our patients on the role of auto SCT for patients with AML we studied consecutive individuals in CR 1 who had tissue compatible siblings and underwent allogeneic (allo) SCT with subjects who had no HLA donor and actually underwent auto SCT. Methods: Patients were in CR 1 following induction combinations containing 7 days of cyatarabine and etoposide with 3 days daunorubicin followed by similar consolidation therapy. The choice for the type of graft was based on availability of HLA identical siblings. Allogeneic donors underwent PBPC mobilisation with filgrastim and for GvHD prophylaxis grafts were exposed ex vivo to alemtuzumab 1mg/1010 mononuclear cells. Patients were prescribed cyclosporin until day 90 post transplant. Individuals lacking a donor underwent PBPC mobilization with etoposide 2 gr/m2 and harvested PBPC were cryopreserved. Patients received similar myeloablative conditioning followed by infusion of the grafts. Patients were stratified by clinical and laboratory factors as well as cytogenetic risk. The end points were TRM, DFS and OS. Results: The median presentation age for both transplant groups was 35 (14-60) years. Of the 112 consecutive patients achieving remission 37 had HLA identical siblings, but 3 relapsed and donors became unavailable in 2. Thus, autologous or allogeneic grafts were actually transplanted to 43 and 32 patients respectively. There was no significant difference in the presentation clinical features, laboratory parameters, marrow morphology or proportion of low and intermediate cytogenetic risk for both transplant options. Treatment mortality as well as relapse rate was similar (14 and 15%; 39 and 27%, respectively). At a median of 1609 and 1819 post transplant days, 56% and 63% in each group survive. In univariate analysis performance status, cytogenetic risk, morphological features of dysplasia, blast count and LDH were significant factors for survival. While for the entire group there was no difference in survival between both modalities, all patients with unfavourable cytogenetics receiving an autologous graft died of disease recurrence (3 year survival 35% vs 0%; p= 0.05). Conclusions: We conclude that patients with AML who have low or intermediate cytogenetic risk undergoing myeloablative conditioning followed by autologous or allogeneic T-cell depleted stem cell transplantation appeared to have similar outcome. However, those with unfavourable karyotype are unlikely to be cured with autologous grafts and are candidates for experimental modalities. Disclosures: No relevant conflicts of interest to declare.

5-Azacytidine Before or After Stem Cell Transplantation in Acute Myeloid Leukaemia (AML) and Myelodysplastic Syndromes (MDS)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4267-4267
Author(s):  
Ana Garrido ◽  
Miguel Ortín ◽  
Rodrigo Martino ◽  
Josep Nomdedeu ◽  
Ana Aventin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Complete Response ◽  
Cell Transplant ◽  
Safe Procedure

Abstract Abstract 4267 The acceptable toxic profile of 5-aza-citidine (5-aza) allows its use in fragile or elderly patients in whom intensive chemotherapy should be avoided. Whether it is possible to take advantage of this low toxicity in patients awaiting for donor search and/or stem cell transplant (SCT) and in those experiencing leukemia recurrences after the procedure remains unknown. We analysed the clinical results of using 5-aza in these two settings to define the feasibility, safety and results of this approach. Patients and methods: From 2007 to 2011, 15 patients (11 males, 4 females) received 5-aza as last treatment prior to an allogeneic SCT (n=13) or as rescue after an early post-transplant relapse (n=2) at our centre. Diagnosis was MDS in 3 cases (median age 62; range 58–63) and AML in 12 cases (median age 58; range 37–67). Patients with MDS received a median of 6 courses of 5-aza (range 3–8) as the only treatment from diagnosis, except for one patient who had received panobinostat prior to 5-aza. Amongst patients with AML, 12 patients received 5-aza either as treatment for AML (2/12) or after remission (8/12) because of the high relapse risk while awaiting for a suitable donor to be found. Two patients with AML received 5-aza as treatment for early post-SCT relapse. AML patients treated with 5-aza before SCT received a median of 5 courses (range 1–19), whilst patients receiving treatment for relapse received 1 and 3 courses, respectively. Ten patients received a nonmyeloablative conditioning regimen, 1 received a conventional conditioning regimen, 2 patients are still in the process of donor search and the other 2 patients received 5-aza after an autologous stem cell transplantation relapse. RESULTS: All MDS patients engrafted and are in complete remission (CR) after a median of 696 days of follow-up (range 377–1227). One of those patients died because of aGvHD. Nine of 12 AML patients receiving 5-aza prior to SCT are alive after a median 373 days follow-up (133–995). One patient showing refractoriness to 3 different lines of treatment died from disease progression after 211 days. All patients receiving 5-aza as treatment for early relapse are dead, 41 and 401 days after starting treatment. Most interestingly, AML patients receiving 5-aza as maintenance of an already-achieved CR while awaiting transplantation did not experience disease progression despite the median time they remained on this treatment was prolonged (9 months). Graft-versus-host disease ≥ grade II was seen in 3 patients. No graft failures were seen and all patients who received an allogeneic stem cell transplantation remain in complete response. CONCLUSION: The use of 5-aza for maintaining or achieving a response in patients with AML who are awaiting SCT is a safe procedure and adds flexibility to schedule the treatment without the need to administer potentially toxic therapy. The use of 5-aza before transplant did not appear to interfere either with engraftment, incidence of GvHD or short-term relapse after transplant. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽  
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.

scholarly journals Defibrotide for Prophylaxis of Hepatic Veno-Occlusive Disease in Autologous, Non-Purged Peripheral Stem Cell Transplantation for High Risk Neuroblastoma Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5910-5910
Author(s):  
Emel Unal ◽  
Nurdan Tacyildiz ◽  
Gulsan Yavuz ◽  
Handan Dincaslan ◽  
Gulsah Tanyildiz ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Occlusive Disease ◽  
High Dose ◽  
Peripheral Stem Cell ◽  
Peripheral Stem Cell Transplantation

Abstract High-dose chemotherapy (HDC) represents the standard of treatment for high-risk neuroblastoma(NBL), hepatic veno-occlusive disease (VOD) is a common, 10-50% and serious complication of haematological stem cell transplantation (HSCT), with up to 90% mortality rates. We planned study to assess whether the use of prophylactic defibrotide in paediatric patients who were heavily treated with chemo-radiotherapy before transplant, and then underwent autologous HSCT. Seventeen patients who underwent autologous, unpurged peripheral stem cell transplantation PBSC with a high risk of developing VOD, between January 2003-July 2014, were given Defibrotide prophylaxis 25mg/kg/day for 30 days, commencing on -1 of conditioning regimen. All patients were stratified by INSS stage, age, N-MYC status. All were treated with six cycles of induction chemotherapy, myeloablative intensification, surgery for primary site, radiation therapy to the primary tumour site plus metastatic sites i.e bone metastases including skull. Meta-iodobenzylguanidin treatment as targeted radiotherapy was given on -21 prior to myeloablative chemotherapy. Oral 13-cis retinoic acid was employed on day +90 post-transplant. CD34+ cell mobilization and PBSC collection was carreid out after two-four cycles of induction cycles. Conditioning regimen and stem cell infusion was done following four-six weeks of last chemotherapy cycle, in order to reduce the toxicitiy. Conditioning regimen CEM consisted Carboplatin, Etoposide, Melfalan. There were no toxic deaths. All of the patients receieved antimicrobial prophylaxis and total parenteral nutrition support when was needed. Myeloid engraftment on day+13, erythroid engraftment on day+18 and thrombocyte engraftment was achieved on day +23. Defibrotide prophylaxis seems to reduce incidence of VOD and is well tolerated. VOD incidence and severity was reduced in the defibrotide group which suggests that defibrotide might be effective in preventing and treating VOD. Sufficiently powered randomised trials are now required to definitively test the role of defibrotide in this setting. Disclosures No relevant conflicts of interest to declare.

Minor Histocompatibility Antigen Mismatches and Graft Versus Host and Relapse in High-Resolution HLA-Matched Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 60-60
Author(s):  
Manuel Cliquennois ◽  
Pascale Cracco ◽  
Dominique Becuwe ◽  
Julia Salleron ◽  
Françoise Dufossé ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Univariate Analysis ◽  
Cumulative Effect ◽  
Marrow Graft ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Grade Ii ◽  
The Impact

Abstract In a fully molecular HLA-matched setting, the outcome of allogeneic stem-cell transplantation (allo-SCT) can be affected by mismatches in minor histocompatibility antigens (mHAs) that might impact on the risk of graft-versus-host (GvH) and graft-versus-leukemia (GvL) effects. The association between mHA disparities and outcome was investigated in 96 consecutive patients who underwent myeloablative HLA-matched allo-SCT (from 69 HLA-identical siblings and 27 HLA-matched unrelated donors, all typed and matched at both allelic levels for HLA-A, -B, -Cw, -DRB1, and -DQB1 loci) for standard-risk hematological malignancy (AML n = 41; ALL n = 29; MDS n = 12; CML n = 8; others n = 6). All patients but 9 received bone marrow graft. Allelic mHAg typing was performed by PCR with sequence-specific primers for 9 autosomally encoded mHA and H-Y (PCR-SSP; Spierings et al. PLoS ONE. 2006 Dec 20; 1:e42). The distribution of autosomal mHAs among donor and recipients conformed to the expected frequencies for this population. As expected, the prevalence of mHAg mismatches was higher in unrelated compared to related recipient/donor pairs (p &lt; .003). In univariate analysis, patients who received a graft with more than 2 mHAg mismatches developed more often grade II-IV acute GvH disease (p = .01; HR=2.92 [1.28–6.64]). In multivariate analysis, HA2 mismatch emerged as an independent determinant of acute GvH disease (p = .05; HR = .42). When only mismatches in the GvL/GvH direction were considered, mismatch for HA-1, that is expressed mainly by the hematopoietic system, tended to influence the incidence of both acute and chronic GvH disease (p = .06; HR=1.47 [0.97–2.21] and p = .049; HR = 1.45 [1.00–2.10], respectively) but also to confer a reduced risk of relapse (p = .07; HR = .58 [0.32–1.05]). Mismatch for HA-8, that has a broad tissue distribution, emerged as an independent risk factor of grade II-IV acute GvH disease (p = .02; HR = 1.77 [1.08–2.89]). This study confirms the impact of mHAg mismatches on patients’ outcome after fully HLA-matched allo-SCT and highlights both the cumulative effect of mHAg disparities on outcome and the distinctive contribution of individual mHAs on GvH versus GvL effects of allo-SCT.

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

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4154-4154 ◽  
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.

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 ◽  
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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