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.

Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Multiple Myeloma (MM): Long Term Follow-up in a Single Centre Series

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4398-4398
Author(s):  
Malek Benakli ◽  
Redhouane Ahmednacer ◽  
Amina Talbi ◽  
Farih Mehdid ◽  
Rachida Belhadj ◽  
...  
Keyword(s):  
Complete Remission ◽  
Median Time ◽  
Acute Gvhd ◽  
Late Onset ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Peripheral Blood Stem Cells ◽  
Heavily Pretreated ◽  
Blood Stem Cells

Abstract Background: RIC allo-SCT has been proposed as a strategy for retaining the graft versus myeloma effect of allo-SCT while decreasing transplant related mortality (TRM). Here, we retrospectively studied a series of 15 patients (pts) with MM treated by RIC allo-SCT. Patients and methods: Between April 2001 and December 2007, 15 pts with MM underwent RIC allo-SCT with an HLA-identical sibling donor. Initially, 8 pts had MM with Ig G, one IgA, 2 light chains, 3 non-secretory and one undetermined. Three pts were stage II and 12 stages III. At time of allo-SCT, 6 pts were in complete remission and 9 in refractory/progressive disease (2 received prior autologous transplants). Median age was 48 years (range, 38–60) and the sex-ratio (M/F) 1,5. 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: 4,5.106/kg (range, 1.92–13). Results: Neutropenia occurred in all pts and the median duration of aplasia was 8 (range, 5–14) days. Only 3 pts (20 %) required red blood cells transfusions and 12 pts (80 %) needed platelets transfusions. Acute GVHD was observed in 6 cases (40 %) including 4 cases of grade II–IV. Eight pts (72 %) had chronic GVHD, of whom 5 with an extensive form. Three pts (20 %) had CMV reactivation at a median time 91 (range, 53–158) days after transplantation. Four pts (26 %) had late onset relapse at a median time of 826 (range, 248–1370) days. TRM was 33 % at one year after RIC allo-SCT. With a median follow-up of 50 (range 14–86) months, 5 pts (33 %) are still alive in complete remission with full donor chimerism. Ten pts (66 %) died (2 early severe infections, 3 acute GVHD, 3 after relapse, one myocardial infarction, and one public highway accident). Overall and progression-free survivals at 7 years are 37,5 % and 31,2 % respectively. Conclusion: This study suggests that RIC allo-SCT is a potential therapy for relapsed MM. However, TRM and relapse remain a matter of concern, likely due to the inclusion of refractory and heavily pretreated pts with many comorbid conditions. Future protocols, should aim for better patient selection, focussing on those pts in first chemosensitive relapse.

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.

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

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.

Fludarabine and Oral Busulfan: A Low Toxicity Conditioning Regimen When Plasma Level Targeting and Intravenous Busulfan Is Not Available. A Brazilian Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5302-5302
Author(s):  
Belinda P. Simoes ◽  
M. Souza ◽  
Marcos Mauad ◽  
Eduardo J.A. Paton ◽  
Fabiano Pieroni ◽  
...  
Keyword(s):  
Plasma Level ◽  
Complete Remission ◽  
Cause Of Death ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Chronic Phase ◽  
Sinusoidal Obstruction Syndrome ◽  
Age Range ◽  
Active Disease

Abstract Fludarabine in combination with intravenous Busulfan has been used to reduce treatment related mortality (TRM) in allogeneic stem cell transplantation (SCT). Considering that busulfan has erratic bioavailability and unpredictable intestinal absorption, previous investigations have used intravenous busulfan with plasma-targeted levels dosing. In Brazil neither intravenous Busulfan nor routine plasma level measurement of Busulfan are available. In this report we retrospectively analyze 74 patients (median age 32 y.o.) submitted to SCT using a Fludarabine and oral Busulfan based conditioning regimen. Forty three patients had acute myeloid leukaemia (AML, age range 5 to 58) and 31 patients chronic myeloid leukemia (CML, age range 19 to 58). Among the AML patients, 44% were in first remission (CR1), 23% in second remission (CR2) and 33% patients had active disease (AD) at the time of transplant. Among CML patients, 65% were in chronic phase (CML-CP), 29% in accelerated phase (CML-AP) and 6% in blast crisis (CML-BC). Fludarabine 30 mg/m2 and oral Busulfan 4 mg/kg was given for 4 days with Cyclosporine A and Methotrexate GVHD prophylaxis. For patients with unrelated donors, ATG were added. All patients engrafted (median 14 days). At a median follow up time of 180 days non-relapse mortality was 5%. Seventeen patients (23%) died (12 AML and 5 CML patients). Among survivors (57 patients), 56 remain in complete remission. One patient with a refractory AML and a complex karyotype relapsed on day +90. One patient died of severe sinusoidal obstruction syndrome (SOS). Acute GVHD occurred in 14 (19%) patients (10 AML and 4 CML) none of them grade III or IV. Chronic GVHD occurred in 11 patients so far, being the cause of death in 2 patients. Major cause of death was relapse of disease in patients transplanted with active disease. Only three AML patients in CR1 died (chronic GVHD, sepsis and fulminant hepatic failure) in contrast to 60% of patients with active disease (88% relapsed). One patient with CML-CP died with a relapse in CML-BC, the remaining 19 (92%) patients are alive in complete remission. One patient transplanted in CML-AP died (cGVHD and zygomykosis) and all patients transplanted in BC died of their disease. Actuarial 1-year overall survival for CML is 92% and 54% (CP and AP/BC respectively, p=0,04) and for AML 72% and 23% (CR1/CR2 and AD, respectively, p=0,005). These preliminary data show that oral Busulfan and Fludarabine can safely be used without plasma level monitoring. The follow up time is short and the effect on the control of CML cannot be concluded. However AML has been effectively controlled as far as patients were transplanted in remission (AML-CR1 and CR2). For patients in more advanced disease stages this regimen is not optimal. However, this regimen is safe and may improve the results in early stages of AML and CML even in countries with limited resources in health care.

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.

Post-Transplant Lymphoproliferative Disorder in Lung Transplant Recipients – a Shift Lo Late Onset Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5075-5075
Author(s):  
Eli Muchtar ◽  
Liat Vidal ◽  
Ron Ram ◽  
Ronit Gurion ◽  
Yivgenia Rosenblat ◽  
...  
Keyword(s):  
Complete Remission ◽  
Disease Progression ◽  
Median Time ◽  
Early Onset ◽  
Lymphoproliferative Disorder ◽  
Lung Transplant ◽  
Late Onset ◽  
Transplant Recipients ◽  
Lung Transplant Recipients

Abstract Abstract 5075 Background: Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication after solid organ transplantation. Most cases of PTLD arise within the first year from transplantation and are associated with EBV infection. However, there are increasing reports on a late onset form of PTLD. Methods: We reviewed all charts of patients undergoing either lung or heart-lung transplantation in a tertiary center in Israel between the years 1997 and 2012. PTLD was defined according to the WHO criteria. We analyzed baseline characteristics, clinical and pathological parameters as well as transplantation outcomes. Results: We identified 9 PTLD patients among cohort of 336 lung and heart-lung transplant recipients (incidence=2. 7%). Additional PTLD patient from another hospital was added for the clinical analysis (10 patients overall). Median age at transplantation of the PTLD patients was 50 (range 11–63) years, compared to 56 (2–69) among the non-PTLD patients (p=0. 04). Idiopathic pulmonary fibrosis was the leading etiology for transplantation among both PTLD and non-PTLD patients (50% vs. 37. 2%, respectively, p=0. 5), while relatively less COPD patients were observed among PTLD patients (10% vs. 34%, respectively, p=0. 28). Median time from transplantation to PTLD diagnosis was 41 (range 3–128) months, being among the longest to be reported in the literature among lung transplant recipients. Three patients developed early PTLD in our cohort, all were pre-transplant EBV seronegative and all were asymptomatic, diagnosed during surveillance chest imaging. In contrast, the seven late-onset PTLD cases were all EBV seropositive prior to transplantation, and were diagnosed after presenting with various symptoms, mainly B symptoms (71%). Overall extra-nodal involvement at presentation was very common for both PTLD forms (90%). While early onset PTLD uniformly involved the transplanted lung, this was relatively rare in the late-PTLD (100% vs. 14%, p=0. 03). According to the WHO classification, all PTLD specimens were monoclonal, based on molecular or light chain immuno-histochemistry. Eight (80%) cases were CD20 positive B cell lymphomas. EBV staining in the specimens was positive in 7 patients, including the 3 early-onset PTLD cases. All patients were treated with reduction of immunosuppression (Table). Other treatment modalities were diverse, including combination chemotherapy (6 patients), rituximab (6 patients), surgery (1 patient) and antiviral treatment (2 patients). 8 (80%) patients attained complete remission. With a median follow-up of 23 months, 6 patients died (3 from chronic rejection of the transplant, 1 from late chemotherapy toxicity, 1 from disease progression and 1 from unrelated cause). The median time from PTLD diagnosis to death was 19 months. Of the 8 patients attaining complete remission, only three patients are alive at the end of follow-up. Conclusion: Our cohort of lung transplant recipients demonstrates a trend of late-onset PTLD. This might be related to the high pre-transplant sero-prevalence to EBV in our cohort (96. 3%), as late-onset PTLD has been reported to be less associated with EBV proliferation. The majority of PTLD patients in our cohort died of treatment-related causes rather than disease progression. Disclosures: No relevant conflicts of interest to declare.

National, Retrospective, Multi-Centre Comparison of Alemtuzumab- Versus ATG-Based Conditioning Regimens in Hematopoietic Stem Cell Transplantation for Aplastic Anemia: A Study From the British Society for Blood and Marrow Transplantation (BSBMT) (CTCR 09-03)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 52-52
Author(s):  
Judith C. W. Marsh ◽  
Rachel M Pearce ◽  
Mickey B Koh ◽  
Daniel Tang ◽  
ZiYi Lim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Aplastic Anemia ◽  
Median Time ◽  
Research Funding ◽  
Graft Failure ◽  
Low Dose ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Conditioning Regimens

Abstract Abstract 52 Background: The ideal conditioning regimen for HSCT in AA is one that achieves engraftment, absence of GVHD and minimal toxicity. Standard conditioning for young patients undergoing matched sibling donor (MSD) HSCT for AA is cyclophosphamide (CY) 200mg/kg and ATG as T-cell depletion (TCD), with ciclosporin (CSA) and methotrexate (MTX) as post graft immunosuppression. For patients who are > 30–40years old receiving MSD HSCT a fludarabine (FLUD)-based regimen with low dose CY (1200mg/m2) and ATG is commonly used. For unrelated donor (UD) HSCT, in Europe, a similar FLUD-based regimen with low dose CY and ATG is commonly used, with addition of low dose TBI (2Gy) for older patients. Long term survival for MSD HSCT is 80–90%, but only 50% for patients aged > 50 years. For UD HSCT, survival is around 75–80%. Chronic GVHD remains a problem, in 30–40% of MSD and up to 50% of UD HSCT. A recent retrospective study of 50 patients transplanted with Alemtuzumab instead of ATG, with CY (1200mg/m2), FLUD, and CSA alone as post graft immunosuppression, showed overall survival at 2 years was 95% for MSD and 83% for UD HCT and only two patients (4%) developed chronic GVHD. Patients: We analyzed data from 159 patients with acquired AA transplanted in the UK, who received either Alemtuzumab or ATG pre-transplant, as part of the conditioning for a first allograft. Patients who received their graft between 1999 and 2009 and had a minimum follow-up of 6months were included in this study. Median age was 20yr (range 1– 67) and M: F ratio was 86: 73. MSD HSCT was performed in 88 (55%) patients, UD HSCT in 65 (41%) including 2 mis-matched, and 6 patients were transplanted from other related donors of which 3 were mis-matched. Source of stem cells was BM in 108 (68%), PB in 39 (25%), BM+PB in 8 (5%) and cord blood in 4 (2%) patients. Conditioning was with Alemtuzumab in 103 (65%) and ATG in 55 (35%), and one patient had received both. CY +/− FLUD was used in 148 and FLUD +/− Melphalan in 11 patients, with addition of TBI in 11 (7%) patients. Median time from diagnosis to HSCT was 6 months (range 0.5–300). Results: Of 159 patients, 137 (86%) are alive at a median follow up of 3.3yr (range 3 months – 10.4 yr). Twenty two patients have died from the following causes of death (not mutually exclusive): infection (n = 15, 68%), GVHD (n = 6, 27%), multi-organ failure (n = 4), lymphoproliferative disorder (n = 1), relapse of breast cancer (n = 1) and one unknown. For all patients, the 1 yr, 5 yr and 10 yr overall survival (OS) were 89% (95% C.I. = 83–93%), 85% (78–90%) and 85% (78–90%), respectively. There was no difference in the 1 yr OS in relation to the method of TCD (Alemtuzumab 91% (84–95%) versus ATG 84% (71–91%), p = 0.1578). Graft failure was observed in 15 (9%) patients. Median time to neutrophil engraftment, defined as ANC > 0.5 × 109/l on first of 3 consecutive days, was 20 days (range 10–89) and platelet engraftment, defined as platelet count > 20 × 109/l on first of 3 consecutive days and no platelet transfusions 7 days prior, was 21 days (range 0–275). Chimerism was full donor in 70 (46%), mixed in 41 (27%), not performed in 37 (24%) and unknown or not evaluable in 2 patients. Acute GVHD grade I-II occurred in 35 (25%) evaluable patients, grade III-IV in 8 (6%). Chronic GVHD was seen in 23 (16%) evaluable patients, limited in 14, extensive in 6 and unknown in 3. Conclusions: From this national study, we report excellent outcomes for HSCT in SAA during the last decade. There was a trend, not significant, for better survival with Alemtuzumab instead of ATG in the conditioning regimen. This is the first reported study comparing outcomes after Alemtuzumab versus ATG based conditioning regimens for SAA. Further analyses, comparing graft failure, acute and chronic GVHD, probability of survival and event - free survival, and patient-related, disease-related and treatment related variables, between Alemtuzumab and ATG-based conditioning regimens, are currently in progress. Disclosures: Marsh: Genzyme: Research Funding. Off Label Use: ATG used as part of conditioning regimen for HSCT in aplastic anaemia. Alemtuzumab used as part of the conditioning regimen for HSCT in aplastic anemia. Pagliuca:Genzyme: Speakers Bureau. Mufti:Celgene: Consultancy, Research Funding.

Determining Late Engraftment Following Single Cord, Unrelated Transplantation: An Analysis of the Eurocord Registry

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 650-650
Author(s):  
Riccardo Saccardi ◽  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Chantal Kenzey ◽  
Wagnara Chaves ◽  
...  
Keyword(s):  
Median Time ◽  
Cumulative Incidence ◽  
Prolonged Exposure ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Clinical Problem ◽  
Clinical Decision ◽  
Time Interval ◽  
Maximum Probability

Abstract Abstract 650 INTRODUCTION. The most prominent clinical problem in CB transplant is a slower engraftment kinetic, as compared to the conventional SC sources. Engraftment failure is usually defined in CB transplantation as a lack of PMN recovery 60 days after transplant, whilst a definition of late engraftment is currently lacking. A late engraftment is a major cause of transplant-related mortality (TRM), due to the prolonged exposure of the recipient to the infective and hemorrhagic risk. After the HSCT, the probability of engraftment at each time interval tends to increase up to a maximum and then gradually decreases, which is typically represented by a sinusoid curve. The decrease of engraftment probability after transplant results in a rapidly increasing risk of TRM; therefore such a turning point should be considered the beginning of a risk phase for late/no engraftment. Therefore, it is important to find the time point after UCBT in which the probability of engraftment will decrease in order to help taking a decision for rescue with a second transplant. We analyzed the clinical expectations beyond this time in a homogenous population of CB recipients. PATIENTS AND METHODS. We investigated the engraftment kinetic in a population of 1215 patients who received a single, unrelated CB transplant for Acute Leukemia (AL) in Complete Remission (CR) following a Myeloablative Conditioning Regimen (MAC). All patients were transplanted in EBMT Centers and reported to the Eurocord Registry from 1994 to 2010. Ratio Lymphoid/Myeloid Leukemias was 769/445, reflecting a major proportion of pediatric patients over adults (857/357). Patients were transplanted in first (43.4%), second (46,6%), or third or subsequent remission (10%), respectively. Median (range) age at transplant was 9.5 (0.3-63) years. Median weight (Kg) at transplant was 33 (5-112). Out of 1089 patients evaluable for HLA-matching, 601 (55.2%) were mismatched for 0–1 loci, 448 (41.1%) for 2 loci and 40 (3.6%) for more than 2 loci. Fifty percent of the patients had a TBI-based myeloablative regimen. Data on TNC counts at freezing of transplanted CBU were available in 963 cases: median and range were 5 (1.1-41.83)x107/Kg. RESULTS. The median FU was 30 months (1-174). At 24 months overall survival was 49±2%, TRM was 32±2%. Median time of engraftment was 24 days (10-133) with a cumulative incidence of 86±1% at day 60. Analyzing the cumulative curve of engraftment, we considered the engraftment probability within intervals of five days after the transplant; in fact the highest probability of engraftment was at day 25 and dropped of 50% at day 42. Among 167 patients (13.7%) who did not engraft at this time, 63 patients (38%) experienced a late engraftment with a median time of 47 days (43-131) after transplant. The cumulative incidence of engraftment at 120 days was 37% and 38% at day 180 without any further increasing later on. Out of the 104 patients who never engrafted, 74 died and major causes of death were bacterial (17%), viral (10%) and fungal (9%) infections, respectively, whilst 30 patients are alive at the last follow up. Information of graft failure treatment was available for 84 patients. Twenty eight did not receive any treatment (25 died at a median time of 80 days form UCBT), 24 had an autologous back up and 32 underwent a second allogeneic HSCT (14 second UCBT, 9 Haplo PBSC and 9 unrelated BMT). Of those 32, 17 patients engrafted, 5 relapsed; 24 died, 8 are alive at last follow up. CONCLUSIONS: The maximum probability of engraftment after UCBT for patients with AL in remission is at day 25 and halves at day 42, thus suggesting that a clinical decision should be made within this period. In particular, rescue actions, such as infusion of another graft, either allogeneic of autologous, should be considered. Such a model can be applied to different subsets of patients and is particularly useful in transplant at high risk of late engraftment such as UCBT. Disclosures: No relevant conflicts of interest to declare.

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