Bone Marrow (BM) Versus Peripheral Blood Stem Cell (PBSC) For Haploidentical Transplantation With Nonmyeloblative (NMA) Conditioning Regimen and Post Infusion Cyclophosphamide

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2119-2119
Author(s):  
Luca Castagna ◽  
Roberto Crocchiolo ◽  
Sabine Furst ◽  
Stefania Bramanti ◽  
Barbara Sarina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Median Time ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Haploidentical Transplantation ◽  
Post Infusion

Abstract Introduction Transplantation from alternative donors has been used since several years for patients with hematological malignancies lacking of HLA identical donors. The Baltimora group pioneered the use of cyclophosphamide (Cy) after haploidentical unmanipulated (BM) stem cells infusion. BM was chosen to reduce the risk of acute and chronic graft versus host disease (GVHD). PBSC could replace BM, fastening engraftment and immunological reconstitution. However, the risk of GVHD could be higher. We retrospectively analyzed a cohort of patients from two institutions, receiving haploidentical transplantation with nonmyeloablative conditioning regimen (NMA) and PSBC or BM, with post-infusion Cy. Patients and Methods From April 2009 to April 2013, 72 patients with poor prognosis hematological malignancies received haploidentical transplantation. Conditioning regimens consisted of Cy 14.5 mg/kg d -5 and -6, fludarabine 30 mg/m2 d-6 to d-2, and low dose TBI (2 Gy) at d-1. GVHD prophylaxis consisted of Cy 50 mg/kg day +3 and +4, tacrolimus (FK, 1 mg total dose, in continuous infusion) until days +180 (Milan cohort) or cyclosporine (CsA, 3 mg/kg) (Marseille cohort) and MMF (15 mg/kg 3 per day) until day +35. FK, CsA and MMF were started at d +5. G-CSF was started at d +5 in all patients. Donors underwent bone marrow harvest under general anesthesia and a total of 4 x 10e8 nuclear cells per kg of recipient was targeted. Unmanipulated bone marrow was used as stem cell support at d0. In Marseille, donors were mobilized using 5 to 6 days of subcutaneous G-CSF (Neupogen®) (10 mcg/kg/day). A minimum of 4 x 10e6 CD34/kg was harvested. Results The median follow-up was 12 months (range: 1-48). For the population as a whole, the median time to ANC more than 0.5 x 10e9/L was 20 days (14-32) and the median time to transfusion-independent platelet (PLT) count was 29 days (14-52). Engraftment results in the two cohorts of patients (BM vs PBSC) were not significantly different [ANC 21 days (14-32) vs 20 days (14-27), and PLT 29 days (16-46) vs 27 days (14-52)]. Overall, aGVHD 2-4 incidence was 27% and cGVHD was 13%. No difference was founded in the two cohorts: aGVHD 2-4 24% vs 33% and cGVHD 11% vs 17%. The 1-year non relapse mortality was 18% overall, and it was not statistically different even if numerically lower in the PBSC group (22% vs 9%). Conclusion This retrospective study showed that there was not significant differences in terms of hematological reconstitution and both acute and chronic GVHD, using unmanipulated BM and PBSC after NMA conditioning regimen and post-infusion Cy. The 1-year NRM, even if not statistically different, was lower with PBSC. These data warrant confirmation with more patients and longer follow-up. Disclosures: No relevant conflicts of interest to declare.

Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Haematological Lymphoid Malignancies: Long Term Follow-up in a Single Centre Series.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4326-4326
Author(s):  
Malek Benakli ◽  
Redhouane Ahmed nacer ◽  
Amina Talbi ◽  
Rachida Belhadj ◽  
Farih Mehdid ◽  
...  
Keyword(s):  
Complete Remission ◽  
Hodgkin Lymphoma ◽  
Median Time ◽  
Conflicts Of Interest ◽  
Late Onset ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Lymphoid Leukaemia ◽  
Autologous Transplant

Abstract Abstract 4326 Background Patients (pts) with recurrent and refractory haematological lymphoid malignancy (HLM) have a very limited survival expectance. RIC allo-SCT has been proposed as a strategy for retaining the graft versus malignancy effect of allo-SCT while decreasing transplant related mortality (TRM). Here, we retrospectively studied a series of 32 pts treated by RIC allo-SCT. Patients and methods Between April 2001 and November 2007, 32 pts with HLM underwent RIC allo-SCT with an HLA-identical sibling donor. Fifteen pts with multiple myeloma, 7 pts with Non-Hodgkin lymphoma, 6 pts with Chronic lymphoid leukaemia, 3 pts with Hodgkin lymphoma and 1 pt with Waldenstrom disease. At time of allo-SCT, 10 pts were in complete remission (3 received prior autologous transplant) and 22 in refractory/progressive disease (6 received prior autologous transplant). Median age was 38 years (range, 28-60) and the sex-ratio (M/F) 2,2. Median time from diagnosis to RIC allo-SCT was 18 (range,6-76) months. The conditioning regimen included Fludarabine 150mg/m2 and Melphalan 140mg/m2. GVHD prophylaxis consisted of association cyclosporine (cSA) and mycophenolate (MMF). All pts received G-CSF mobilised peripheral blood stem cells, with a median CD34+ cell count: 6,2.106/kg (range, 1.9-13,6). Results Neutropenia occurred in all pts (100%) and the median duration of aplasia was 9 (range, 5-16) days. Only 10 pts (31 %) required red blood cells transfusions and 23 pts (71 %) needed platelets transfusions. Acute GVHD was observed in 15 cases (47 %) including 10 cases of grade II-IV. Fifteen pts (75 %) had chronic GVHD, of whom 9 with an extensive form. Four pts (12 %) had CMV reactivation at a median time 60 (range, 52-80) days after transplantation. Six pts (18 %) had late onset relapse at a median time of 13 (range, 4-45) months. TRM was 43 % at one year after RIC allo-SCT. With a median follow-up of 60 (range 18-97) months, 12 pts (37,5 %) are still alive in complete remission with full donor chimerism. Twenty pts (62,5 %) have died (5 early severe infections, 10 GVHD, 3 after relapse, one myocardial infarction, and one accident). Overall and progression-free survivals at 8 years are 31 % and 30 % respectively. Conclusion This study, after a large follow-up, suggests that RIC allo-SCT is a potential therapy for refractory or progressive HLM. However, TRM is still high likely due to the inclusion of refractory and heavily pretreated pts with many comorbid conditions. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Tranplantation (allo-SCT) for Adult Patients with Active Refractory/Relapsed Hematological Malignancies: a Survey From the Societe Française De Greffe De Moelle Et De Therapie Cellulaire (SFGM-TC).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3456-3456
Author(s):  
Patrice Chevallier ◽  
Noel Milpied ◽  
Karin Bilger ◽  
Gérard Socié ◽  
Ibrahim Yakoub-Agha ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conflicts Of Interest ◽  
Phase 1 ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Best Supportive Care ◽  
Adult Patients ◽  
Peripheral Blood Stem Cells ◽  
Hematological Diseases

Abstract Abstract 3456 Patients with active refractory/relapsed hematological diseases have a very poor outcome. Best supportive care or investigational therapies in phase 1 trials are usually proposed to these patients. However, some previous data suggested that allo-SCT might be an efficient therapy even in the setting of chemorefractory disease, because long-term immune-mediated disease control can be achieved in some patients after allo-SCT. The aim of this study was to evaluate on a large series the outcome of adult patients with active refractory/relapsed hematological diseases at time of allo-SCT and to determine which sub-group would most benefit from such approach. Between 2005 and 2009, 861 patients with various hematological diseases (AML, n=323; ALL, n=43; MDS, n=129, CMML, n=12; MPS, n=110; CML, n=28; NHL, n=100; HL, n=40; myeloma, n=36; CLL, n=24; and other, n=16) were treated with allo-SCT, and reported to the SFGM-TC Registry. Per study criteria, all patients presented with active refractory or relapsed disease at time of transplant. This series included 517 males (60%) and 344 females (40%). The median age at transplant was 50 (range, 16–71) years. The median interval between diagnosis and transplant was 17 (range, 1–99) months. 32% of patients failed at least one prior SCT (Autologous or allogeneic prior to allo-SCT). 350 (41%) patients received allo-SCT from an HLA-matched sibling donor, while the remaining 59% received an allogeneic graft from a matched unrelated or mismatched donor. The stem cell source was mainly peripheral blood stem cells (n=617; 72%). Bone marrow was used in 139 patients (16%), and cord blood in 107 patients (12%). Myeloablative conditioning regimen was used in 328 patients (38%), and various reduced-intensity regimens were used in other cases (62%). With a median follow-up of 290 (range, 1–1854) days after allo-SCT, engraftment was observed in 88% of cases. Grade II-IV and grade III-IV acute GVHD occurred in 35% (n=301) and 17% (n=144) of patients, respectively. Chronic GVHD was observed in 185 patients (21%; limited: n=77; extensive: n=82; missing data: n=24). At last follow-up, 347 patients (40%) were still alive (of whom 297 were in CR; 86%). 246 patients (28.5%) died of disease progression, and 232 patients died of transplant-related causes (NRM: 27%). The Kaplan-Meier (KM) estimates of overall survival (OS) at one and 2 years were 39% (95%CI, 36–43%) and 31% (95%CI, 28–35%), respectively. Of note, in patients with lymphoma (n=140), OS at 1 and 2 years were 57% (95%CI, 48–66%) and 49% (95%CI, 40–58%) versus 36% (95%CI, 32–40%) and 27% (95%CI, 23–31%), respectively, in all other diagnoses (P=0.00004). In a Cox multivariate analysis accounting for relevant factors, a diagnosis of lymphoma (NHL or Hodgkin) was the most significant factor associated with improved survival (RR=1.68; 95%CI, 1.3–2.2; P=0.0001). Despite its retrospective nature and the inherent selection biases, in case of availability of suitable donor, this data support the use of allo-SCT in adult patients with active refractory/relapsed hematological diseases, especially in patients with lymphomas. Results are expected to be further improved with the advent of novel conditioning regimens and maintenance therapies after transplant that are currently tested as part of prospective studies. Disclosures: No relevant conflicts of interest to declare.

Nonmyeloablative Allogeneic Transplantation (NMT) for Relapsed Follicular Lymphoma (FL): Continuous Complete Remission with Longer Follow-Up.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 485-485
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
Martin Korbling ◽  
Chitra Hosing ◽  
Luis Fayad ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Time ◽  
De Novo ◽  
Chronic Gvhd ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Study Entry ◽  
Two Samples

Abstract NMT carries the promise of long-term disease control in FL by graft-versus-lymphoma immunity. We investigated the long-term efficacy of this strategy. Between March 1999 and April 2005, 47 consecutive patients were enrolled, ranging in age from 33 to 68 years (median, 53 years). The time from diagnosis to transplantation ranged from 7 months to 24 years (median, 3 years). All patients had recurrent chemosensitive FL. Each patient had received 2 to 7 (median, 2) chemotherapy regimens. Eight patients (17%) had failed a prior autologous transplantation. At the time of transplantation, 29 patients (61%) were in PR, and 18 (31%) were in CR. The conditioning regimen consisted of fludarabine (30 mg/m2 daily for 3 days), cyclophosphamide (750 mg/m2 daily for 3 days) and rituximab (Khouri, Blood 2001). This was followed by an infusion of HLA-matched hematopoietic cells from related (n=45) or unelated donors (n=2). Tacrolimus and methotrexate were used for graft-versus-disease (GVHD) prophylaxis. All patients achieved CR after transplantation. The median time to achieve CR in patients who had evidence of active disease at study entry was 5.5 months. Two relapses occurred. One was observed at 18 months; this patient responded to DLI with a continuous CR at 24+ months. The other patient who developed a relapse, was found to be simultaneously in graft failure 20 months after his transplantation. That patient was treated with rituximab and is still in CR at his last follow-up 4 years later. Eighteen patients had PCR evidence of bcl-2 translocation in the bone marrow at study entry. There were a total of 100 bone marrow post-treatment PCR samples available for analysis. Ninety eight samples that are drawn at a median time of 45 months after transplantation (range 4 months to 72 months) showed a negative PCR result. Two samples from 2 different patients were PCR-positive early after transplant; they became PCR-negative 3 months later. With a median follow-up time of 56 months (range, 19–94 months), the estimated overall survival (OS) and current progression-free survival (CPFS) rates at 6 years were 85% (95% confidence interval [CI], 71%–93%) and 83% (95% CI 69%–91%), respectively. The incidence of acute grade II–IV GVHD was 11% (95% CI, 31%–66%). The incidence of chronic extensive and limited GVHD, was 51% (95% CI, 44%–78%). Of the 28 patients who developed chronic GVHD, 20 (71%) had a de novo onset. The median time of onset of chronic GVHD was 262 days after transplantation, and the OS of patients with chronic GVHD was 89%, with a median follow-up time of 57 months (range, 19–94 months). Only five patients of the whole study group are still receiving immunosuppressive therapy at the time of their last follow-up. In conclusion, the longer follow-up of our study does provide further insight into long-term disease activity and regimen toxicity of NMT for FL, laying the groundwork for prospective comparative trials. We believe that the described results are a step forward toward finding a cure for this disease.

Comparison of PBSC Vs Cord Blood (CB) As Stem Cells Source for Reduced-Intensity Conditioning Regimen (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) in Adult Patients with Haematological Diseases: A Single Centre Analysis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3108-3108
Author(s):  
Amandine Lebourgeois ◽  
Marion Loirat ◽  
Benoit Tessoulin ◽  
Elsa Lestang ◽  
Pierre Peterlin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cord Blood ◽  
Median Time ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Single Centre ◽  
Stem Cell Source

Abstract Abstract 3108 Introduction: RIC regimens are increasingly used for allo-SCT in older patients or patients with co-morbidities. The FB2 regimen (Fludarabine 120–150 mg/m2 + I.V. Busulfan 6.4 mg/Kg + ATG 5 mg/Kg) using PBSC as stem cell source is currently the most widely used RIC regimen in many European centres. On the other hand, in patients without a suitable HLA-matched donor, the use of umbilical cord blood stem cells for allo-SCT (uCBT) is increasingly considered, especially using the RIC regimen developed by the Minneapolis group. Series comparing PBSC vs CB as stem cells source for RIC allo-SCT are still scarce and using various RIC regimens before allo-SCT. Patients and Methods: This retrospective single centre analysis compared two homogeneously treated cohorts of patients who had received between January 2007 and November 2010 in our department either a FB2/PBSC allo-SCT (n=52, males: 61%; median age: 59 years (range: 22–70)) or a FC-TBI/uCBT (Fludarabine 200 mg/m2 + Cyclophosphamide 50 mg/Kg + TBI 2 Grays regimen; n=39, males 49%; median age 56 years (range: 22–70). Except for age (p=0.03), there were no significant differences between the 2 groups regarding patients and diseases characteristics: gender (p=0.22), interval between diagnosis and transplant (PBSC: 9 months vs CB: 10 months, p=0.85), disease type (PBSC: myeloid disease 63% vs CB: 67%, p=0.75), status at transplant (complete remission PBSC: 77% vs CB: 67%, p=0.28), prior auto-SCT (PBSC: 35% vs CB: 33%, p=0.90). Donors in the PBSC group were as follows: sibling donors, n=30; HLA-MUD n=20, mismatched unrelated n=2. All patients from the CB group received 2 CB units (HLA matching 4/6 n=25; 5/6 n=53). As for GVHD prophylaxis, patients received cyclosporine (CsA) alone in case of an HLA-identical sibling donor, and CsA+ mycophenolate mofetyl in all other cases. None of the patients from the PBSC group received G-CSF after transplant, while it was administered to all CB recipients. Results: Median follow-up was respectively 19 and 20 months for the PBSC and the CB groups (p=NS). Engraftment and median time for neutrophils recovery were similar between the 2 groups: PBSC: 96% vs CB: 90%, p=0.22; and 17 days (range: 0–39) vs 16 days (range: 8–60), p=0.88, respectively. The median time for platelets recovery (>20000/mm3) was significantly higher in the CB group: 38 days (range: 13–150) vs PBSC: 0 days (range: 0–186) (p<0.0001). The cumulative incidences of grade II-IV and grade III-IV acute GVHD were comparable between both groups: PBSC: 31% and 15% vs CB: 26% and 8% (p=0.72 and p=0.28) as also the 2-years incidence of chronic GVHD: PBSC: 35% vs uCBT: 25%, p=0.54. 2-years NRM was significantly higher after uCBT: 26% vs 6%, p=0.02. Finally, there were no differences between the two groups in terms of 2-years OS, DFS and Relapse Incidence: PBSC: 62.3% vs CB: 60.8% (p=0.51); 58.7% vs 50.4% (p=0.43) and 36% vs 23% (p=0.31). In multivariate analysis, the source of stem cells (CB) remains associated with NRM (HR: 0.16, 95%CI: 0.05–0.5, p=0.001) but was not predictable for survivals. Conclusion: Our study suggests that RIC uCBT is a valid alternative in patients lacking an HLA-matched related or unrelated donor and candidate for RIC allo-SCT. Prospective and randomized studies are warranted in order to establish the definitive role of uCBT, especially in patients with acute leukemia, where CB cells may offer a rapidly available source of stem cells in diseases with high tumor kinetics. Disclosures: No relevant conflicts of interest to declare.

Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Multicenter Open French Study In High-Risk pediatrics

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 534-534
Author(s):  
Catherine Paillard ◽  
Patrick Lutz ◽  
Guy Leverger ◽  
Gerard Michel ◽  
Pierre Bordigoni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Platelet Count ◽  
Solid Tumors ◽  
Median Time ◽  
Graft Failure ◽  
Hematological Malignancies ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Abstract Abstract 534 Introduction: There is increasing information about reduced intensity conditioning regimen AlloHSCT (Allogeneic Hematopoietic Stem Cell Transplantation) in children. The safety of this approach is now well established but data regarding efficacy are limited and the role in pediatric cancer has yet to be defined. Materiels and methods: We report results of a French pediatric AlloHSCT protocol with ATG-fludarabine (180 mg/m2) - Busilvex (3.2 at 4.8 mg/kg/d for 2 days) conditioning regimen. Related, unrelated bone marrow (BM) and Peripheral blood stem cell (PBSC) donors and Cord blood units (CB) were allowed. In case of CB a TBI 2 grays, Cyclophosphamide 50 mg/kg, Fludarabine 100 mg/m2 conditioning regimen was recommended. GVH prophylaxis consists in cyclosporine alone. A rapid discontinuation of systemic immunosuppression and re-injecting donor lymphocytes to initiate graft-versus-tumor effect are based on tumor assessment and blood chimerism. Inclusion criteria are children with malignancies that can be potentially cure by allograft but a conventional conditioning regimen being impossible due to toxicity and children with solid tumor or hematological malignancy remaining unresponsive to the reference strategies according to French best practices in pediatrics. Results: From April 2007 to April 2010, 40 RIC AlloHSCT were performed in 10 different French pediatric graft centers: 13 Hodgkin Lymphoma, 7 acute myeloblastic leukaemia, 2 acute lymphoblastic leukaemia, 6 neuroblastoma, 8 rhabdomyosarcoma, 3 desmoplastic tumor and 1 Ewing sarcoma. Median age at transplantation was 15 years and median time from diagnosis to transplant was 18 months. Before transplant, 15 patients are in complete response and 25 patients (14/18 solid tumors) have active disease (11 progressive, 14 partial response). 21 had already received a myeloablative therapy (18 autograft and 3 allograft). Graft source was PBSC in 17 cases (7 related and 10 unrelated), BM in 18 (10 related and 8 unrelated), and 5 CB. The RIC Bu-flu conditioning regimen permits rapid engraftment without major toxicity contrary to the Cy-TBI in CB. 1 patient had primary graft failure: 1 CB and 5 patients experienced secondary graft failure: 3 CB, 1 PBSC and 1 BM. Median time to reach an ANC of 0.5 109/l was 16 days. Median time to reach a platelet count of 20 × 109/l was 2 days. Platelet count did not decrease below 20 109/l in 10 allografts. At day 30 post-transplant, chimerism is mainly donor for 30 and partial for 6 children. At day 100 post transplant, 4 out of 6 with initial mixed chimerism were converted into full donor chimerism. 8 patients received DLI and 17 patients experienced acute graft versus host disease (GvH) (2 grade IV and 15 grade ≤ II). A low day 365 TRM of 5% is reported in these heavily pre-treated patients. With a median follow-up of 15 months, the estimated 2 yr overall survival (OS) was respectively 57 % (71% for hematological malignancies and 42% solid tumors) (fig 1) and event free survival (EFS) 36% (50% for hematological malignancies and 19% solid tumors). Univariate analysis of EFS and OS showed no effect of related versus unrelated stem cell sources and BM versus PBSC. Our analysis identified a group of patients, who had no measurable disease at transplant, with a 2 yr OS and EFS of 86%. In term of efficacy, we observe a graft versus lymphoma effect in patients with advanced active Hodgkin lymphoma. Concerning solid tumors, all children included had a very bad prognosis and detectable disease before transplant. Our results may suggest that an immune-mediated effect cannot be excluded in some refractory solid pediatric tumors particularly in neuroblastoma. The main cause of failure of this approach is disease progression. Immunologic approaches after transplantation may help cure more of these very-high-risk patients. Conclusion: Even if further follow up is needed, this prospective study suggest that RIC regimen provides promising outcome in children previously not eligible for myeloablative AlloHSCT. This study “RICE” was registered at www.clinicaltrials.gov as NCT 007 50 126 Disclosures: No relevant conflicts of interest to declare.

scholarly journals Feasibility and Outcomes of Haploidentical Transplantation for Elderly Patients with Advanced Hematological Malignancies: The MD Anderson Cancer Center Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1245-1245 ◽  
Author(s):  
Sameh Gaballa ◽  
Piyanuch Kongtim ◽  
Gabriela Rondon ◽  
Julianne Chen ◽  
Uday Popat ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Cancer Center ◽  
Platelet Recovery ◽  
Matched Donor ◽  
Active Disease

Abstract Background Haploidentical stem cell transplantation (HaploSCT) is an acceptable option for younger patients (pts) with advanced hematological malignancies without a human leukocyte antigen (HLA)-matched donor; however, it remains unclear whether older pts would benefit from such a transplant. Here, we report the outcomes of pts age 55 years or older who received a T-cell–replete HaploSCT with a reduced-intensity conditioning regimen using fludarabine-melphalan and post-transplant cyclophosphamide (PTCy) as previously described by us. Methods We retrospectively analyzed data from 30 pts (20 [67%] with acute myeloid leukemia [15 with high-risk disease], 4 [13%] with myelodysplastic syndromes, 3 [10%] with lymphoma, and 3 with other diagnoses) who received their first HaploSCT between 2009 and 2014. Twenty-one pts (70%) received conditioning with fludarabine 40 mg/m2 (Days -6, -5, -4, -3) and melphalan 100 mg/m2 (Day -8) with thiotepa 5 mg/kg (Day -7) or 2 Gy total-body irradiation (FM100). Nine pts (30%) received a higher melphalan dose of 140 mg/m2. GVHD prophylaxis consisted of PTCy 50 mg/kg on day +3 and +4 after HaploSCT and tacrolimus and mycophenolate for 6 and 3 months, respectively. Sixteen pts (53%) were in remission at the time of transplant. Donors were children (83%) and siblings (17%). All patients but 1 received bone marrow as a stem cell source. Results Thirty pts (57% men) with a median age of 61 years (range, 55-69 years) received a HaploSCT between 2009 and 2014. One pt had early death on day +7 from a viral infection. All other pts engrafted successfully (100% engraftment), with 84% achieving 100% donor chimerism at day 30. The median times to ANC and platelet recovery were 19 days (range, 13-27 days) and 28 days (range, 19-46 days), respectively. CMV reactivation occurred in 21 pts (70%) and was treated preemptively. The rates of grade II-IV and III-IV acute GVHD at day 100 were 30% and 10%, respectively; chronic GVHD occurred only in 3 pts (10%) (2 limited, 1 extensive). After a median follow-up duration of 18 months, 18 pts (60%) were alive and disease-free. The 1- and 2-year overall survival rates were 60% and 55%, respectively (62% for pts in complete remission and 41% for pts with active disease at 2 years, log-rank= 0.23), and the 1- and 2-year progression-free survival rate was 55% (63% at 1 and 2 years for pts in complete remission and 40% for pts with active disease at 1 year) (Figure). The 100-day and 2-year cumulative incidences of non-relapse mortality were 17% and 21%, respectively (12% and 18%, respectively, for pts in remission at transplant). Causes of death included relapsed disease (n=6), infection (n=3), chronic GVHD (n=1), and regimen toxicity (n=1). Conclusions HaploSCT for older pts up to age of 70 years is associated with low rates of acute and chronic GVHD, acceptable NRM, and excellent survival. Age alone does not appear be a barrier against successful transplantation from a haploidentical donor and should be offered to all pts in need of a transplant without an HLA-matched donor. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Successful Result of 113 Patients for Refractory/Recurrent Leukemia By Allogeneic Hematopoietic Cell Transplantation and Prophylactic Immunotherapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5856-5856
Author(s):  
Jingbo Wang ◽  
Xiaojun Huang ◽  
Ying Hu ◽  
Song Xue ◽  
Haoyu Cheng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Transplantation ◽  
Median Time ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Prolymphocytic Leukemia ◽  
Significant Difference

Abstract Objective: To retrospectively evaluate the results of allogeneic hematopoietic stem cell transplantation for Refractory/Recurrent leukemia. Methods: From July 2012 to May 2016, total 113 patients with Refractory/Recurrent leukemia were enrolled, including 31 cases of ALL, 73 cases of AML and 8 cases of CML-BP, 1 case of Prolymphocytic leukemia. The average leukemia burden was 51% (10-99) in bone marrow before conditioning. Myeloablative conditioning regimens consisted of 13 cases of BuCy, 47 cases of TBI/FLAG, 28 cases of TBI/Cy, and 16 cases of FLAG that followed by reduced-intensified BUCY, 9 cases of CLAG/BuCy. Transplant types included sibling HLA-identical allo-HSCT (n=22) and relative HLA-haploidentical HSCT (n=91). All patients received cyclosporine A, MMF and methotrexate for GVHD prophylaxis. Analyzed outcomes were hematological engraftment, incidence of acute and chronic GVHD, incidence of CMV/EBV infecton, incidence of relapse, and nonrelapse mortality (NRM), Overall survival (OS) and Disease-free survival (DFS). Results: The median mononuclear cells and CD34+ for transfusion were 8.83 (7.02-11.64) ×108/Kg and 2.91 (0.8-8.32) ×106/Kg. 111 patients achieved stable engraftment, 2 patients died of infection before engraftment. The median time of ANC≥0.5×109/L was 16 days(8-29) and the median time of platelet ≥20×109/L was 22 days (8-150). On day 28postallogeneic transplant, 110 patients were in complete remission of bone marrow, 1 patient was in hematologic relapse. Immunity residue were negative in 107 patients and positive in 4 patients. 62 patients developed acute GVHD, the accumulative incidence of aGVHD was (57.6±4.8)%, the accumulative incidence of II-IV grade aGVHD was (47.2±4.8)%, and the accumulative incidence of III-IV grade aGVHD was (25.2±4.1)%. 62 patients developed cGVHD (43 patients extensive, 19 patients limited), the accumulative incidence of cGVHD was (70.2±6.6)% and for extensive type, the accumulative incidence was (43.6±5.2)%. The accumulative incidence of CMV infection was (42.3±4.7)%, and the accumulative incidence of EBV infection was (4.5±2)%. 10 patients developed virus cystitis, and the accumulative incidence was (9.1±2.1)%. The median follow-up time post transplantation was 10 months (1-46), 35 patients occurred hematologic relapsed and the accumulative incidence of relapse was (39.7±5.9)%. For AML, ALL and CML-BP patients, the accumulative incidence of relapse were (33.8±6.9)%, (56.6±11.7)% and (25±15.3)%respectively (p>0.05). On median follow up (10 months), 49 patients died and 64 patients survived. The cause of death included relapse (28 cases), infection (6 cases), GVHD (11 cases) diffuse alveolar hemorrhage (2cases), radiation enteritis (1 case), and TMA (1 case).Among 64 survirors, two-year accumulative incidences of OS were (49.3±5.7)%, and two-year accumulative incidences of LFS were (45.1±5.4). The two-year accumulative incidences of OS for AML, ALL and CML-BP patients were ( 52.4±7.1)%, (28.1±9.7)%,and (87.5±11.7)%respectively (p>0.05). The two-year accumulative incidence of LFS for AML, ALL and CML-BP patients were (49.8±6.5)%, (24.7±9.1)%, and (70±18.2)%respectively (p>0.05). Incidence of relapse, OS and LFS were similar in different conditioning cohorts (p>0.05). There was no significant difference in the incidence of relapse, OS and LFS over two years among patients with C-Kit, FLT3, MLL and without such genes(p>0.05). There is significant difference in incidence of relapse, OS and LFS among patients with different leukemia burdens(p<0.01). Patients with leukemia burden at 10-19% has lower relapse rate but higher OS and LFS compared to patients with leukemia burden at 80%. Incidence of relapse, OS and LFS for the prophylactic immunotherapy cohort were 32.9%, 61.1% and 57.6% respectively, compared to 45.2%, 35.8% and 35% for non prophylactic immunotherapy cohort (p<0.01). Incidence of relapse , OS and LFS for the cGVHD cohort were 12.9%, 68.4% and 66.2% respectively, compared to 78.7%, 13.9% and 12.8% for non cGVHD(p<0.01). Incidence of relapse , OS and LFS for extensive cGVHD cohort were 12.3%, 62.1% and 61.8% respectively, compared to 58.8%, 31.4% and 31.2% for non extensive cGVHD(p<0.01) Conclusion: Our clinical results have shown that the salvaged HSCT is a promising modality for treatment of Refractory/Recurrent leukemia. Especially for Refractory/Recurrent AML and CML-BP. Disclosures No relevant conflicts of interest to declare.

scholarly journals Improved Outcomes in Patients with Thalassemia Major Transplanted with Peripheral Blood and Marrow Grafts in Comparison with Cord Blood and Bone Marrow Grafts from Sibling Donors

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 847-847
Author(s):  
Qiao chuan Li ◽  
Jian ming Luo ◽  
Zhong ming Zhang ◽  
Lian jin Liu ◽  
Ling ling Shi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cord Blood ◽  
Graft Rejection ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Matched Sibling

Abstract Background: Thalassemia major (TM) is a fatal genetic disease currently only curable with allogeneic stem cell transplantation. This is limited by the lack of suitable donors and the quantity of collected stem cells, and is often complicated by graft rejection and graft versus host disease (GVHD). Methods: The aim of the study was to compare the outcomes of TM patients transplanted with matched sibling cord blood (CB) and bone marrow (BM) grafts vs. matched sibling peripheral blood (PB) stem cell and BM grafts. The trial was designed as a prospective, open-label, single-center clinical protocol, where 204 TM patients were enrolled between January 2007 and November 2015 and transplanted with either PB + BM (n=99) or CB+BM (n=105), from an HLA-identical sibling donor. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University and was registered at the Chinese Bone Marrow Transplant Registry (CBMTR). The primary end point was 2-year thalassemia free survival(TFS). Secondary end points included 2-year overall survival (OS), the cumulative incidence of GVHD, transplant related mortality (TRM), graft rejection (GF).The conditioning regimen were:1) busulphan (BU) (1.25 mg/kg) given orally four times per day for 4 days or 1mg/kg given intravenously (IV) four times per day for 4 days (day -9 to day -6); 2) fludarabine (FLU) (50mg/m2/day) given IV for 3 days (day -12 to day -11); 3) cyclophosphamide (CTX) (50 mg/kg/day) given IV for 4 days (day -5 to day -4); 4) anti-thymocytes globulin (ATG, Genzyme ) (2.5 mg/kg/day) given IV for 4 days (days -4 and day -1). All patients were placed on 30 mg/kg hydroxyurea orally once daily for 2-3 months before transplantation.GVHD prophylaxis consisted of a combination of cyclosporin A, methotrexate and mycophenolate mofetil regimen. [BMT 2009; 43(1):61-67]. Results : Patient and donor characteristics, and transplantation outcomes are listed in Tables 1 and 2, respectively. Data cut off for survival follow-up was March 31, 2016. The median follow-up time was 26 months (range, 4 months -105 months). Both neutrophil as well as platelet engraftment occurred significantly faster in the PB+ BM group than the CB+BM group (11 days vs. 13 days, P=0.001 and 15 days vs. 25 days, P=0.001, respectively). The rate of GF was the same in both groups (1.0%). The cumulative incidence of grade II-IV acute (a) GVHD and extensive chronic (c)GVHD in the PB+ BM group was higher than the CB+BM group: aGVHD=15.5% vs 1.0%, P=0.001; cGVHD= 6.4% vs. 0%, P=0.013. The cumulative rates of TRM at 2 years remained significantly lower in the PB+BM group compared to the CB+BM group with 2.0% and 12.5%,(P=0.005), respectively . Both OS and TFS at 2 years favored the PB +BM group compared to the CB+BM group : OS=98% vs. 86.5%,P=0.003;TFS= 97% vs. 86.5%, P=0.008.(Fig 1) Conclusion: Our results demonstrate that grafts composed of PB + BM had superior overall outcomes compared to CB + BM grafts, as evidenced by faster engraftment and lower TRM of the former despite substantially lower aGVHD and cGVHD rates of the latter. The mixed stem cell populaitons and the high cell dose achieved with the use of 2 different graft sources, toghether with the conditioning regimen used likely contributed to the superior outcomes seen with this regiem. This strategy could be of great benefit for the treatment of patient with TM and other benign hematologic disease. Disclosures No relevant conflicts of interest to declare.

Outcome of Allogeneic Hematopoietic Cell Transplantation (HCT) for Patients with Severe Aplastic Anemia (SAA) above the Age of 40 Years.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3019-3019
Author(s):  
Dario Sangiolo ◽  
Rainer Storb ◽  
Wendy Leisenring ◽  
George Georges
Keyword(s):  
Median Time ◽  
Immune Suppression ◽  
Chronic Gvhd ◽  
Immunosuppressive Treatment ◽  
Conditioning Regimen ◽  
Term Survival ◽  
Allogeneic Hct ◽  
Number Of Patients ◽  
Clinical Records

Abstract Allogeneic HCT for SAA is definitive curative therapy for this otherwise fatal hematologic disease. For younger SAA patients, long-term survival of approximately 90% can be expected after HCT from HLA-identical siblings with cyclophosphamide/ antithymocyte globulin (CY/ATG) conditioning and post-grafting methotrexate/cyclosporine (MTX/CSP) immunosuppression. Most transplant center guidelines and many published reports restrict allogeneic HCT to SAA patients under the age of 40 years, due to concern of increased morbidity and mortality from HCT in older patients. We reviewed the clinical records of all 20 patients with a diagnosis of SAA who were treated with HCT from an HLA-identical sibling at the Fred Hutchinson Cancer Research Center from July 1988 to January 2006 and were above the age of 40 years at the time of HCT. The conditioning regimen consisted of CY/ATG for all but 2 patients who did not receive ATG. MTX and CSP were used as post grafting immunosuppression. The median age of the 10 men and 10 women was 47 (40–63) years. The median time from diagnosis to HCT was 2.7 (0.8–48.5) months. Ten patients had previously received immunosuppressive treatment and all 20 patients had received multiple red blood cell and platelet transfusions before HCT. The median follow-up of surviving patients was 86 (range, 17–194) months after HCT. One patient had graft rejection on day 28 and is alive and well following reconditioning and repeat marrow grafting from original donor. The incidence of acute grades II and III graft-versus-host-disease (GVHD) was 41% and 6%, respectively, the incidence of chronic GVHD (cGVHD) was 37% (6 patients). Overall survival was 70% (fig. 1). Three patients died before engraftment: from preexisting disseminated aspergillosis (n=1), congestive heart failure likely related to CY toxicity (n=1) and preexisting disseminated candidiasis (n=1) on days 2, 3 and 6, respectively. Three patients died from infections on days 83, 179 and 223; in the latter 2 cases, the infections were related to cGVHD and its treatment. The median time to discontinuation of immune suppression was 6 (range, 6–46) months (fig. 1). At last follow-up, 2 patients remain on immune suppression for treatment of cGVHD at 24 and 41 months, respectively. Three patients experienced avascular joint necroses 3, 6 and 9 years after HCT; they had cGVHD (n=2) and/or received extensive steroid treatment before HCT (n=2). Two patients developed superficial basal cell carcinoma at 5.5 and 15 years after HCT. Our data suggest that allogeneic HCT from sibling donor can be successfully extended to SAA patients older than 40 years. Although the number of patients are limited, survival after HLA-identical sibling HCT appears superior to published results of immune suppression therapy for patients >40 years of age. Pre-HCT cardiac screening is indicated to minimize the risk of conditioning related toxicity. Improved treatment to effectively treat or prevent cGVHD and associated infections remain important issues. Figure Figure

Low Relapse without Excessive Transplant-Related Mortality Following Allogeneic Stem Cell Transplantation in Patients with High Risk Secondary Acute Myeloblastic Leukaemia and Myelodysplastic Syndromes, Long-Term Outcomes in a Single Centre Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4308-4308
Author(s):  
Jean El-cheikh ◽  
Luca Castagna ◽  
Sabine Furst ◽  
Catherine Faucher ◽  
Benjamin Esterni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Allogenic Stem Cell Transplantation ◽  
Related Mortality

Abstract Abstract 4308 Allogenic stem cell transplantation (Allo-SCT) as a therapy for secondary acute myeloid leukaemia (sAML) and myelodisplastic syndromes (MDS) is the most powerful treatment option. However, (Allo-SCT) is also complicated by a high risk for treatment-related morbidity and mortality. We analysed retrospectively the data of 70 patients transplanted at our institution from June 1995 to december 2008, 44 patients (63%) with sAML and 26 patients (37%) with MDS was treated with (Allo-SCT); median age at diagnosis was 41 years, (15-70), and the median age of 42, 5 years (16-70) at transplantation; The conditioning regimen was myeloablative combining (cyclophosphamide and TBI) in 16 patients (23%) and 54 patients (77%) was with a reduced intensity conditioning (RIC) regimens combining fludarabine, busulfan, and antithymocyte globulin; 11 patients (16%) were infused with bone marrow (BM), 55 patients (79%) peripherical blood stem cells (PBSC), and 4 patients (5%) cord blood cells; in 49 cases (70%) donor was a HLA identical sibling and in 21 (30%) was a matched unrelated donor; 41 patients (59%) carried high risk cytogenetic features, like (7q-, 5q-, > 3 alterations), while was normal in 24 patients (34%), and in 5 patients (7%) was unknown. Disease status at transplantation was as follow: CR in 24 patients (34%), 34 patients (49%) was refractory or in progression after treatment, and 12 patients (17%) was with a stable disease. With a median follow-up of 55 months (3-150), 30 patients (43%) are alive, the overall survival OS at 2 years and 5 years was 48 % and 39% respectively, and after ten years of follow up, OS was 30%, 95%CI [17.8-50.8]. We observed also that 26 % of refractory patients and 54% of patients in CR are alive at five years of transplantation. The probability of progression after transplantation at five and ten years was 31% with 95%CI [20.-46.5]. 2 years and 5 years treatment related mortality (TRM) was 23% and 26% respectively, and no modification at ten year, 95%CI [14.3-37.3]. TRM occurred in 16 patients (23%). Cause of death was; infections in 5 patients (7%), GvHD in 3 patients (4%), GvHD and infection in 3 patients (4%), multi organ failure (MOF) in 5 patients (7%). In multivariate analysis; OS, PFS or TRM, were not influenced by donor type (HLA id sibling vs others), conditioning regimen (RIC vs MAC), and stem cell source (bone marrow vs PBSC). Allogenic stem cell transplantation can be considered as a good option for the treatment of patients with high risk sAML and MDS when compared with the remission rate at five years of the other nonallogeneic SCT therapies. Disclosures: No relevant conflicts of interest to declare.

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