Multi-Center Prospective Trial on Conditioning with Treosulfan, Fludarabine and ATG Before Allogeneic HSCT from Unrelated Donors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4949-4949
Author(s):  
Mauricette Michallet ◽  
Quoc-Hung Le ◽  
Anne Thiebaut ◽  
Sophie Ducastelle ◽  
Franck E. Nicolini ◽  
...  
Keyword(s):  
Prospective Trial ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Low Risk ◽  
Unrelated Donor ◽  
Match Analysis ◽  
Hematopoietic Stem ◽  
Unrelated Donors ◽  
Grade Ii

Abstract This prospective multi-center trial (MiniMud) concerns 27 patients (13 females, 14 males - 56 years[18–65]) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated donors. The diagnosis and disease status pre-transplant were AML (n=12; 5 CR1, 7 CR2), ALL (n=1; 1 CR2), MM (n=5; 3 PR2,1 PR3, 1 PR4), NHL (n=4; 1 CR1, 2 PR3, 1 PR4), MPS (n=3; 2 stable disease (SD), 1 Relapse), acute RAEB (n=1; 1 progressive disease (PD) and CLL (n=1; 1 PR2). In total, 14 patients were in CR, 9 in PR, 2 in SD, 2 in PD. The median interval between diagnosis and transplant was 27 months [5;171], 24 patients received PBSC and 3 received bone marrow from unrelated 10/10 antigen HLA-identical (high-resolution level). All patients received Fludarabine 30 mg/m2/dx5d, Treosulfan 12 g/m2/dx3d and ATG 2,5 mg/kg/dx3d. After transplant, we observed 2 graft failures, 7 patients developed an AGVHD ≥ grade II (30%). Only 23 patients were eligibile to be analysed after 3 months of follow-up post transplant, 7 patients developed cGVHD (30%) (5 limited and 2 extensive), 12 patients died (7 from TRM causes and 5 from relapse) and 12 patients are alive in CR with a median follow-up of 14 months. Among the global population we defined a low risk subgroup: 17 patients [12 AML (5 CR1, 7 CR2), 1 ALL (CR2), 3 MM (3 PR2) and 1 NHL (CR1)], 2 patients presented an AGVHD ≥ grade II (13%). With a median follow-up of 18 months, 2 patients had a follow-up of less than 3 months, 3 patients developed a cGVHD (20%), 6 patients died (40%) and 9 patients are alive in CR. At one year, the probability of overall survival (OS) and event-free survival (EFS) were 50.4% [32;79], 40% [23;70] for the total population and 60% [37;96], 51.5% [29;90] for the low risk subgroup respectively. To try to demonstrate if Treosulfan allowed a better transplant outcome we performed a paired match-analysis [center and 4 out of 5 other parameters (age, gender, HSC, pre-transplant status and diagnosis] comparing our Treosulfan series and RIC transplants receiving Fludarabine, Busulfan and ATG (2.5–12.5mg/kg) from the SFGM-TC registry. This paired match-analysis found only RICT from related donors in the SFGM-TC database and showed no difference in term of OS and EFS between our unrelated donor-Treosulfan and related donor-SFGM-TC series. Figure Figure Figure Figure In conclusion, these results demonstrate that Treosulfan appears to be a very promising drug that could be included in the conditioning regimen before HSCT from either related or unrelated donors.

Updated Analysis of Hematopoietic Stem Cell Transplantations after Reduced Intensity Conditioning Regimen (RIC HSCT) for Hematological Malignancies from the Société Française de Greffe de Moelle Osseuse et de Thérapie Cellulaire (SFGM-TC) Registry.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 45-45 ◽  
Author(s):  
Mauricette Michallet ◽  
Quoc-Hung Le ◽  
Thomas Prebet ◽  
Mohamad Mohty ◽  
Jean Michel Boiron ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Grade Ii ◽  
The Impact ◽  
Global Population

Abstract This report updates a retrospective study from SFGM-TC registry concerning 738 patients who underwent RIC HSCT for hematological malignancies [280 F, 458 M, median age: 51 years (1–72)] between 1997 and 2004. The diagnosis were 173 AML, 40 ALL, 68 MDS, 152 NHL, 36 HD, 45 CLL, 70 CML, 154 MM; 332 patients have been previously transplanted. At time of conditioning, 261 patients were in CR, 224 in PR and 253 in progressive disease (PD). Peripheral blood stem cells (PBSC) were used in 574 patients and bone marrow in 164 patients from 655 HLA related donors and 83 unrelated donors. As conditioning, 152 patients received fludarabine and TBI (2 grays), 300 patients fludarabine, busulfan and anti-thymocyte globulins (FBS) (ATG 1d: 57, 2 d: 84, 3 d: 58, 4 d: 18, 5 d: 83) and 286 patients an other regimen. As GVHD prophylaxis, 722 patients received a cyclosporine A (CsA) based regimen. After transplant, 252 patients (35%) in the global population developed an acute GVHD ≥ grade II (grades III and IV: 116) and 208 patients (37%) in the PBSCT population (grades III and IV: 100). A chronic GVHD was present in 258 patients (38%) in the global population (115 limited and 143 extensive) and 221 patients (42%) in the PBSCT population (95 limited and 126 extensive). With a median follow-up of 27 months, the 3-year probability of overall survival (OS) and event-free survival (EFS) for the global population was 38% (33–44) and 28%(24–34) and for PBSC SCT patients 39%(33–46) and 32%(27–39) respectively. The 3-year probability of OS varied according to diagnosis (CLL: 62%, NHL:50%, CML:44%, MM:41%, MDS:37%, AML:26%, ALL:20%) and cGVHD (no:28%, yes:61%). The cumulative TRM incidence was 12% at 1 year and 13% at 3 years. A multivariate analysis was performed studying pre and post transplant factors for OS, EFS and GVHD:. Table 1 summarizes all variables showing a significant impact on OS and EFS. Furthermore, analyses showed the impact of one variable on AGVHD and cGVHD for PBSCT population: FBS with ATG 1day vs 2 days [HR:1.56(1.19–2.04) p=0.001, HR:1.50(1.14–1.97) p=0.003]. In conclusion, besides the influence of known factors on OS and EFS after RIC HSCT, this study pointed out, on a large series with a long-term follow-up, the major impact of disease status, acute and chronic GVHD and demonstrated the important role of ATG duration on GVHD incidence. Table 1: Multivariate analyses OS/EFS Variables OS (HR) p EFS (HR) p Conditionning :FBS ATG 1d vs 2 d Global 1.47 (1–2.2) 0,05 NS PBSC 1.6 (1.03–2.49) 0,04 NS FBS ATG 5d vs 2 d PBSC NS 1.13(1.04–1,24) < 0.01 PD vs CR Global 1.22 (1.1–1.32) < 0.01 1.15 (1.07–1.25) < 0.01 PBSC 1.2 (1.1–1,3) < 0.01 1.14 (1.05–1.24) < 0.01 Previous HSCT: yes vs no Global 1.27 (1.02–1,59) 0,04 1.25 (1.01–1.55) 0.04 AGVHD : Grade II vs 0-I PBSC 1.21 (1–1.47) 0,05 NS AGVHD : Grade III-IV vs 0-I Global 1,28 (1,14–1,43) < 0.01 1.12 (1–1.25) 0.04 PBSC 1.3 (1.14–1.47) < 0.01 1.13 (1–1.28) 0.05 cGVHD : yes vs no Global 0.2 (0.14–0.28) < 0.01 0.25 (0.19–0.35) < 0.01 PBSC 0.19 (0.13–0.28) < 0.01 0.25 (0.18–0.34) < 0.01

scholarly journals Outcome of Severe Aplastic Anemia Post Allogenic Stem Cell Transplant with Mycophenolate and Calcineurin Inhibitor for Graft Versus Host Disease Prophylaxis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4879-4879
Author(s):  
Omar Albanyan ◽  
Hyejeong Jang ◽  
Seongho Kim ◽  
Andrew Kin ◽  
Asif Alavi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Matched Donor

Abstract Introduction: Severe aplastic anemia (SAA) is a rare hematopoietic stem cell disorder characterized by hypocellular marrow and pancytopenia. Multiple factors play an important role in treatment approach include age, comorbidities, degree of pancytopenia and availability of stem cell donor to either immunosuppression irrespective (IST) or allogenic hematopoietic stem cell transplant (alloSCT). The use of nonmyeloablative conditioning regimen has improved the outcomes, however the choice for post-transplant GVHD prophylaxis remain a topic of debate. The use of mycophenolate mofetil (MMF) has been used as an alternative for methotrexate (MTX) as has shown to be associated with lower incidence of mucositis and shorter time to engraftment. Methods: We retrospectively evaluated consecutive adult patients with SAA who underwent alloSCT at Karmanoc Cancer Institute. All patients received fludarabine, cyclophosphamide and antithymocyte globulin for conditioning regimen with calcineurin inhibitors (CNI) and MMF for GVHD prophylaxis. MMF was started at day -3 at 15 mg/kg three times daily and stopped at day +30 in the absence of active GVHD. The primary objectives were to estimate cumulative incidence of acute (aGVHD) and chronic GVHD (cGVHD) and overall survival (OS). Secondary objectives were to evaluate time to engraftment, days of hospitalization and incidence of mucositis. Results: From January 2005 and May 2019, 33 patients with SAA underwent alloSCT. Patient characteristics are detailed in Table 1. Median age was 36 years (range, 18-71). Twenty-seven patients received bone marrow stem cells (82%) and six patients received peripheral blood stem cells (18%). Thirty patients (91%) received 8/8 HLA matched donor and three patients (9%) received 7/8 HLA matched donor. Sixteen patients (48%) received stem cells from sibling donor and 17 patients (52%) received stem cells from unrelated donor. Thirteen patients (39%) had received IST prior to alloSCT, and 20 patients (61%) received upfront alloSCT. For GVHD prophylaxis all patients received MMF and CNI (tacrolimus=32, and cyclosporine=1). Median time from diagnosis to transplant was 15.8 months for patients who received IST prior to alloSCT and 2 months for patients who received upfront alloSCT. Median time to platelet engraftment was 13.5 days and neutrophil engraftment was 12 days, while one patient experienced graft failure. The median number of days for hospital stay were 25 days. Four patients (11%) developed grade I-II mucositis, no grade III-IV mucositis was observed in the first 30 days and 6 patients had CMV reactivation. The 100-day cumulative incidence rate of grade II-IV aGVHD was 21.2% (95% CI, 9.2 - 36.5), grade III-IV aGVHD was 9.1% (2.3-21.9) and 1-year CIR of cGVHD was 21.2% (95% CI, 9.2-36.5). Comparing patients who received IST prior to alloSCT versus upfront alloSCT, the 100-day CIR of grade II-IV aGVHD was 30.8% (95% CI, 8.2 - 56.5) and 15% (95% CI, 3.6 - 34.0), respectively, (Gray p=0.26) and the 3-year CIR of cGVHD was 39.6% (95% CI, 13.1 - 65.5) and 27.8% (95% CI, 9.2 - 50.3), respectively, (Gray p=0.37). Comparing patients who received alloSCT from related versus unrelated donor, 100-day CIR of II-IV aGVHD was 12.5% (95% CI, 1.9 - 33.6) and 29.4% (95% CI, 10.2 - 51.9), respectively, (Gray p=0.26), and the 3-year CIR of cGVHD was 34.2% (95% CI, 11.4 - 58.9) and 29.4% (95% CI, 10.1 - 52.0), respectively (Gray p=0.90). Median follow up of surviving patient was 5 years (95% CI, 3.1-6.8). Three-year OS was 87% (95% CI, 75.7- 99.9) and median OS was not reached. Six patients died by the time of the analysis, one patient died from graft failure (86 days after transplant from 8/8 HLA MUD), two patients died due infectious complications (808 days and 1637 days after transplant), three patients died due to multiorgan failure (215, 297 and 1097 days after transplant). Conclusion: Our data with use of CNI and MMF for GVHD prophylaxis for SAA following alloSCT with nonmyeloablative conditioning regimen showed that the rate of mucositis was low, engraftment time was rapid, and hospitalization was short, while OS, rates of acute and chronic GVDH were comparable to previously published rates with CNI and MTX-based GVHD prophylaxis. Figure 1 Figure 1. Disclosures Modi: Genentech: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees. Deol: Kite, a Gilead Company: Consultancy.

Results of T Cell Depleted (TCD) Myeloablative Hematopoietic Stem Cell Transplants (HSCT) in Patients with Hematologic Malignancies ≥ 55 yrs of Age.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3660-3660
Author(s):  
Ann A. Jakubowski ◽  
Esperanza B. Papadopoulos ◽  
Hugo R. Castro-Malaspina ◽  
Katharine Hsu ◽  
Miguel-Angel Perales ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
High Risk Patient ◽  
Disease Status ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Conditioning Regimens ◽  
Good Risk

Abstract Allogeneic HSCT remains the only curative therapy for many patients(pts) with hematologic diseases. Studies have suggested that older pts experience greater toxicity from the intensive chemo-radiotherapy used in myeloablative conditioning regimens. As a consequence, many older pts are now offered non-myeloablative transplants (NMAT) for malignant conditions where a graft vs. tumor effect (GvT) is expected to provide the antitumor effect in place of the chemo-radiotherapy. Unfortunately, graft vs. host disease (GvHD) remains a common occurrence after conventional transplants, occurring more frequently in older pts and unrelated donor transplant recipients, resulting in significant morbidity and mortality. Furthermore, the efficacy of NMAT is limited by the disease status at time of transplant and by the susceptibility of the hematologic disease to a GvT effect. TCD of hematopoietic stem cell grafts offers an alternative to older pts, in particular those requiring unrelated donor transplants (URD), with the advantage of a reduced incidence of GvHD. From 1995–2005, 57 patients ≥55 yrs received myeloablative TCD transplants at our institution. The median age was 58.2 (range 55–69.2) yrs. Stem cell sources were TCD bone marrow, PBSC or both. Thirty-seven received transplants from related donors (RD), including two mismatched, and 20 received transplants from unrelated donors (URD), 9 of whom were mismatched. In addition to their advanced age, many of these pts were considered high risk based on the status of disease, HLA mismatch, and history of previous therapy. Twenty-three pts were considered “good risk” by disease status (CML-CP1, AML-CR1, CR2) and 34 pts were considered poor risk (&gt;CML-CP1, &gt;AML CR2, MDS, NHL, &gt;ALL CR1, ABL.) BM was TCD by soybean agglutination followed by sheep red blood cell rosetting (E), and PBSCs by CD34+ selection and E-rosetting. Conditioning regimens included total body irradiation (TBI) in addition to thiotepa and cyclophosphamide, or thiotepa and fludarabine. The non-TBI preparative regimen consisted of busulphan, melphalan and fludarabine. Anti-thymocyte globulin was used as rejection prophylaxis for all TCD transplants until 2001 when it was eliminated from the TBI containing regimen for matched RD transplants. A total of 25 pts (15 matched RD and 10 URD, 6 of whom were mismatched) are alive following TCD transplants with a median follow up of 24 mos. for RDs and 12 for URDs. Of the survivors, 2/10 URD and 14/15 RD recipients received TBI containing regimens based on the triage system at our center. Three pts with CML-CP1, one with CML-acc and one with AML-CR1 showed evidence of minimal residual disease, received donor leukocyte infusions and subsequently achieved longterm continued CR. The incidence of post-transplant GvHD was low despite the high number of mismatched URD transplants - 1 Grade IV (RD), 2 Grade 3 and 1 Grade 1 (URD). The 100 day mortality was 15%. Overall and current disease free survival for ‘good risk’ patients based on disease status is 58% for RD and 60% for URD. Although longer follow up is necessary to confirm these results, the promising DFS rates in association with a low incidence of GvHD in this older and relatively high risk patient population support further investigation of myeloablative TCD HSCT in these patients.

Durable Remission with Decreased HTLV-I Proviral Load after Reduced-Intensity Stem Cell Transplantation (RIST) in Patients with Adult T-Cell Leukemia/Lymphoma (ATL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3347-3347
Author(s):  
Ryuji Tanosaki ◽  
Kisato Nosaka ◽  
Shin Mineishi ◽  
Shin-ichiro Mori ◽  
Sung-Won Kim ◽  
...  
Keyword(s):  
Conditioning Regimen ◽  
Disease Status ◽  
Donor Lymphocyte Infusion ◽  
Acute Type ◽  
Adult T Cell Leukemia ◽  
Trial Testing ◽  
Grade Ii ◽  
Related Donor ◽  
Healthy Carriers

Abstract Background. ATL is an HTLV-I-associated hematological malignancy. The majority of ATL patients are not curable using current chemotherapy with median survival time of 13 months. Recently, patients undergoing allo-SCT with conventional conditioning regimen were reported to have a 3-year overall survival (OS) rate of 45%, however, with high transplant-related mortality (TRM) rate as much as 40% (Fukushima T. Leukemia19:829, 2005). Since most ATL patients are over 50 years old with various complications, limited numbers of patients are eligible for conventional transplant. We have already conducted a phase I multi-center trial testing the feasibility of RIST in ATL patients, where 2-year OS was 33% and some differences in the outcome were suggested among participating institutes. Hence, we investigated the efficacy of RIST performed exclusively in our single institute (NCCH, Japan). Patients and Methods. Between Oct 2000 and Jun 2005, 16 ATL patients underwent RIST from a related donor. Since 3 have been enrolled into an on-going multi-center trial, 13 patients were analyzed in this retrospective study, including 3 who were enrolled into the above-mentioned multi-center trial (Okamura J. Blood105;4143, 2005). Median age was 51 years old (range, 44–61), 8 males and 5 females, and 8 were of acute type and 5 of lymphoma. The disease status at transplant was 3 CR, 7 PR and 3 primary refractory. Three donors were HTLV-I healthy carriers. Eleven were HLA 6/6, 2 were 5/6, 12 were PBSCT and 1 was BMT. Conditioning regimen was fludarabine 30 mg/m2 x6, busulfan 4 mg/kg x2 with (n=5) or without (n=8) rabbit ATG 2.5 mg/kg x2. Prophylaxis of GVHD was CSP alone. Results. Engraftment was rapid (median, 11 days) in all cases, and there was no TRM. Acute GVHD of grade II–IV developed in 7, and chronic extensive GVHD in 5. Eleven patients achieved CR after RIST, and 6 relapsed or progressed, among whom 2 achieved CR after cessation of CSP, donor lymphocyte infusion and local irradiation, and have been disease-free for more than 1 year. Ten patients are alive, 9 without disease, with median follow-up time of 26 mos (range, 4–45 mos). HTLV-I proviral titers determined using real time PCR decreased after RIST and became undetectable in 8 out of 13 patients. In 3, including one transplanted from an HTLV-I carrier donor, anti-HTLV-1 antibody transiently decreased and became nearly undetectable. Conclusions. RIST is feasible and safe in ATL patients, and it has not only an anti-ATL but also an anti-HTLV-I activity. This is the first report documenting the efficacy of RIST for ATL in terms of survival and remission durability. Figure Figure

Decreased Relapse Rates without Excessive Transplant Related Mortality Following Cord Blood Transplantation (CBT): A Matched Cohort Analysis Comparing Myeloablative Cord, Matched Unrelated, and Mismatched Unrelated Donor Transplants.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 968-968 ◽  
Author(s):  
Jonathan A Gutman ◽  
Wendy Leisenring ◽  
Frederick R. Appelbaum ◽  
Ann E Woolfrey ◽  
Colleen Delaney
Keyword(s):  
Cord Blood ◽  
Blast Crisis ◽  
Cohort Analysis ◽  
Disease Status ◽  
Unrelated Donor ◽  
Matched Cohort ◽  
Unrelated Donors ◽  
Relapse Rates ◽  
Related Mortality

Abstract We conducted a matched cohort analysis comparing relapse rates and outcomes for patients receiving transplants from cord blood, matched unrelated donors, and mismatched unrelated donors following myeloablative conditioning in our center’s recent experience. Between April 2006, when our current cord blood protocols opened, and February 2008, 26 consecutive patients underwent CBT following conditioning with 13.2 Gy TBI, 120 mg/kg cyclophosphamide (CY), and 75 mg/m2 fludarabine (FLU) for acute leukemias in morphologic CR (n=24) or chronic myeloid leukemia not in blast crisis (n=2). Twenty-three patients received two units (5 of whom had one of the two units ex vivo expanded) and three received single units. Matching between units and patient was 4/6:4/6 (n=10), 4/6:5/6 (n=5), 5/6:5/6 (n=7), 6/6:6/6 (n=1), and single 5/6 (n=3). For paired analysis with each cord patient, waiver of consent was obtained from the IRB and one matched 10/10 unrelated donor patient (MURD) and one mismatched (9/10 n=23, 8/10 n=3) unrelated donor patient (MMURD) was selected from our center’s database on the basis of identical disease status and similar age without knowledge of transplant outcome. All unrelated donor patients underwent myeloablative transplantation following conditioning with CY/TBI or busulfan (BU)/CY between November 2001 and February 2008 (median April 2005). Patients were matched for disease type, cytogenetic risk status, minimal residual disease status (MRD), and, for patients beyond CR1, time from diagnosis to relapse. Specific diseases and disease status were ALL n=10: CR1 n=8 (MRD n=3), CR2 n=1, CR3 n=1 (MRD n=1), Philadelphia chromosome positive n=3; AML n=14: CR1 n=8 (MRD n=1), CR2 n=6 (MRD n=2); CML n=2 (CP1 n=1, CP2 following blast crisis n=1). Median ages and range for patients were: CBT 23 (0.6–42), MURD 25 (1–41), and MMURD 25 (1–48), and median differences in age between the cord recipient and their unrelated donor matched pairs were 7.8 and 4.6 years for MMURD and MURD, respectively. Median follow-up for surviving cord patients is 16 months (range 7.5–26). There has been only 1 relapse among cord patients versus 8 relapses among MURDs and 5 relapses among MMURDs. Transplant related mortality (TRM) between each group is comparable. Cause specific hazard for relapse is significantly decreased when comparing cords to MURDs by logrank test (p=0.014) and trends toward decrease when comparing cords to MMURDs (p=0.068) (Figure 1). Two year cumulative incidence (CI) of relapse is 3.8% (95% CI 0.3–16.4) for cord patients, 31.4% (95% CI 14.9–49.6) for MURDs, and 21% (95% CI 7.6–38.9) for MMURDs. Two year CI of TRM is 21.6% (95% CI 7.5–40.4) for cord patients, 22.9% (95% CI 8.3–41.8) for MURDs, and 31.8% (95% CI 15–50.1) for MMURDs. Previous data suggest that double unit CBT, as compared to single unit CBT, may markedly reduce relapse rates. The majority of CBT patients included in this analysis underwent double unit CBT, and this strategy may contribute to our observations. Additionally, myeloablative MURD and MMURD TBI regimens at our center involve 12 Gy in contrast to the 13.2 Gy in our CBT regimens. This may also account to some degree for lower relapse rates. Larger numbers and longer follow-up will be needed to confirm these observations, but the possibility of decreased relapse rates without increased TRM is promising. Growing inventories of high quality cord blood units coupled with ongoing improvements in supportive care for CBT patients should lead to continued expansion of the role of CBT. Figure 1: Relapse and TRM following transplantation. Figure 1:. Relapse and TRM following transplantation.

The Use of Bone Marrow Graft for Hematopoietic Stem Cell Transplantation From Matched Unrelated Donors After Reduced Intensity Conditioning Regimen Improves Survival : Analysis of the Societe Française De Greffe De Moelle Et De Therapie Cellulaire.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 873-873
Author(s):  
Andrea Toma ◽  
Marie-Lorraine Balère-Appert ◽  
Jean-Michel Boiron ◽  
Pierre Bordigoni ◽  
Gerard Socie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multivariate Analysis ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Reduced Intensity Conditioning Regimen ◽  
Unrelated Donors ◽  
Grade Ii

Abstract Abstract 873 The use of peripheral blood stem cells (PBSC) for hematopoietic stem cell transplantation (HSCT) is associated with a higher risk of chronic graft versus host disease (GvHD) but its impact on survival is not clear since it may favor a greater graft versus leukemia (GvL) effect. However, in the context of HSCT from unrelated donors (UD), the balance between GvH and GvL may differ from the context of sibling donors and thus the use of PBSC may be deleterious. In this retrospective study, we analyzed 103 patients from the french registry who received a graft from an UD after a reduced intensity conditioning regimen (RIC) to evaluate the role of various parameters including the source of stem cells on the outcome. Seventy-one D/R pairs (69%) were 10/10 HLA match at the allelic level. Mismatches concerned 5, 6, 15, 2 and 7 D/R pairs for HLA-A, -B, -C, -DRB1 and -DQB1, respectively. The median age was 46 years (18-67). All patients had hematologic malignancies: AL (n=35), MM (n=18), CLL (n=5), NHL (n=11), HD (n=9), CML (n=12), MDS (n=9), and MPS (n=4). 39% of the patients were in an advanced phase of the disease at time of HSCT. The conditioning regimen was Fluda/TBI 2Gys for 26 patients, Bu/Fluda/ATG for 24 patients, Fluda/Melph for 16 patients and others for 37 patients. Overall, anti-thymocytes globulins (ATG) were part of the conditioning regimen for 77% of patients. The source of stem cells was PBSC for 65 patients and bone marrow (BM) for 38 patients. The median follow up of the cohort is 61,3 months (1,2-113,7). The results showed that 95% of patients engrafted. Five patients did not engraft (4 in the BM group and 1 in the PBSC group). Acute GvHD grade II to IV and grade III/IV occurred in 47% and 19% of patients, respectively. The risk of developing chronic GvHD was 49% at 2 years. Overall survival (OS) was 36% at five years. The median disease free survival (DFS) was 55 months among the 36 patients alive. We performed univariate and multivariate analysis of factors susceptible to impact on GvHD and survival. The multivariate analysis included the impact of HLA mismatch, disease status, diagnosis, source of stem cells, patient's and donor's ages. This multivariate analysis performed on the global population shows a trend towards an improved OS with the use of BM instead of PBSC. However, when focusing the multivariate analysis on the 71 patients transplanted with a 10/10 match donor, the most potent factor influencing the outcome is the use of BM which is associated with an improved OS (p=0.03) and DFS (p=0.02), less acute GvHD grade II-IV (p=0.05), or grade III/IV (p=0.05) and less chronic GvHD (p=0.05). These results suggest that the use of BM as the source of stem cells should be reconsidered in the context of matched UD after RIC transplantation. Disclosures: No relevant conflicts of interest to declare.

Phase II Prospective Multicenter Study of Treosulfan Based Reduced Intensity Conditioning In Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies From 10/10 HLA Identical Unrelated Donor

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2353-2353 ◽  
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Stephane Morisset ◽  
Nathalie Tedone ◽  
Jacques-Olivier Bay ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Cumulative Incidence ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Grade Ii ◽  
Reduced Intensity

Abstract Abstract 2353 Background: The key point in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is to find the optimal balance between the graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect particularly in the unrelated HSCT settings, without forgetting the important role of conditioning. Objective: To evaluate the toxicity and efficacy of a new reduced intensity conditioning regimen including Treosulfan, followed by allo-HSCT from a 10/10 HLA identical unrelated donor. Materials and Methods: This prospective study included adult patients presenting a hematological malignancy in need of allo-HSCT using a 10/10 HLA identical unrelated donor. Accepted diagnoses were: CML in 1st chronic phase (CP) resistant to imatinib, in 2nd CP or in complete remission (CR) after blast crisis. Multiple myeloma (MM) or chronic lymphocytic leukemia (CLL) in stage B or C in response after relapse post-auto-HSCT. Acute lymphocytic or myeloid leukemia (ALL, AML) patients in CR1 at high risk or <CR1. Myelodysplasic syndrome (MDS) with poor prognostic factors. The conditioning included: Treosulfan 12g/m2/day intra-venous (day-6 to day-4), fludarabine 30mg/m2/day intra-venous (day-6 to day -2) and ATG 2.5 mg/kg/day (day-2 to day-1). GVHD prophylaxis used cyclosporine A oral (5mg/kg/day) or iv. (3mg/kg/day) from day-1. Peripheral stem cells after mobilization by G-CSF were used as HSC source. Results: Between February 2005 and July 2009, 56 patients were included in 5 different French centers, 30 (54%) males and 26 females with a median age of 57 years (18-65.5). There were 38 (68%) myeloproliferative disorders [29 AML (14 in CR1, 14 CR2 & 1<CR), 8 MDS (1CR1 and 7<CR) and 1 CML in CR1] and 18 (32%) lymphoprolifative disorders [9 MM in PR, 6 CLL (2CR1 & 4PR) and 3 ALL(1CR1 & 2CR2)]. Among 45 explored for cytogenetics, 23 (51%) were normal and 22 with poor prognostic. Before transplantation, two patients did not receive any previous treatment, 21 received 1 line, 22 two lines and 11 > 2 lines. For sex-matching, 49% of patients were sex-mismatched (half of them were F>M). For CMV, 43% were -/-, 25% +/+, 28% +/&minus; and 1% -/+. For ABO matching, 52% were compatible, 24% major incomp. & 24% minor incopm. The median time between diagnosis and allograft was 15 months (4-168). The median number of infused CD34+ cells was 6.5 × 106/Kg(1-17.2) Fifty-four (96%) patients engrafted with a median time to neutrophils (>0.5G/l), and platelets (>50G/l) recovery of 16 days (4-86), 11 (4-82) respectively. Seventeen patients developed aGVHD grade ≥II (8 grade II, 2 grade III & 7 grade IV) with a cumulative incidence at 3 months of 31% (25-38). The cumulative incidence of cGVHD was, at 12 months: 32% (25-39) limited and 6% (2-10) extensive; at 18 months: 34% (27-47) limited and 8% (5-12) extensive. After a median follow-up of 13 months (1-57), the median overall survival (OS) was not reached with a 3 years probability of 52% (38-71). The median time of event free survival (EFS) was 15 months (8 - 57) with a 3-years probability of 47% (35-64). The cumulative incidence of relapse at 3 years was 25% (19-31) and the cumulative incidence of transplant-related mortality (TRM) at 12, 18 and 36 months was 20% (16-27), 23% (16-29) (same at 18 & 36 months) respectively. At the last follow-up, 22 patients died, 7 due to relapse and 15 due to TRM (5 pneumonia, 4 GVHD, 1 secondary malignancy and 6 other causes). We showed in a univariate analysis a higher 3-years OS of patients in CR1 (65%) compared to those <CR1 (44%) at transplantation with a significant better benefit for AML patients (76%). Patients with active cGVHD seem to benefit for the GVL effect on OS with a high significant difference (HR=0.2 (0.1-0.6) p=0.002). The multivariate analysis studying age, sex matching, ABO compatibility, CMV matching, type of disease, CD34+ cells number, cytogenetics, number of previous treatments, disease status and interval diagnosis-allo-HSCT showed: a negative significant impact of both minor ABO incompatibility (p<0.001) and CMV+/&minus; (p=0.01) on OS, a negative significant impact of patients <CR (p=0.03) on relapse. There was no impact of studied factors on TRM. Conclusion: We showed very promising results in terms of OS, relapse and TRM with an impressive GVL effect, in heavily pre-treated patients and transplanted using unrelated donors. Treosulfan appears to be a good choice for conditioning especially with a better outcome in AML patients in CR1. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Haploidentical Hematopoietic Stem Cell Transplantation in Pediatric Patients with Acquired Severe Aplastic Anemia: Collaborative Study of Three Eastern Asian Countries

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2556-2556
Author(s):  
Ho Joon Im ◽  
Kyung Nam Koh ◽  
Yoshiyuki Takahashi ◽  
Chengjuan Luo ◽  
Seiji Kojima ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Pediatric Patients ◽  
Medical Center ◽  
Collaborative Study ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Grade Ii

Abstract Haploidentical hematopoietic stem cell transplantation (HHCT) is indicated for patients with severe aplastic anemia (SAA) who need emergent HCT or for those with refractory SAA who lack a matched related or unrelated donor.°°We evaluated the outcomes of children and adolescents with acquired SAA who received HHCT at three transplant centers in Eastern Asia. This collaborative study reports the feasibility and efficacy of HHCT in children and adolescents with acquired SAA. Between May 2006 and February 2014, 33 patients received HHCT at Asan Medical Center Children’s Hospital in Seoul (n=18), Shanghai Children’s Medical Center (n=8), and Nagoya University Hospital (n=7). Eighteen patients received in vitro T cell-depleted transplantation (TCD-HHCT) and 15 received a graft without in vitro manipulation (non-TCD-HHCT). Of the 33 patients, 27 had failed immnosuppressive therapy prior to HHCT. The donors were the mother in 15 patients, the father in 14, and a sibling in four. The conditioning regimen consisted of fludarabine (FLU), cyclophosphamide (CY), and rabbit ATG (r-ATG) with or without total body irradiation (TBI) in 18 patients who received TCD-HHCT. In the 15 patients who received non-TCD-HHCT, FLU/CY/ATG was used as a conditioning regimen for eight patients and FLU/melphalan/r-ATG/TBI for seven patients. Among the 33 patients, 31 achieved neutrophil engraftment at a median of 12 days (range, 9–34 days) after HHCT. Two patients (one with TCD-HHCT and one with non-TCD-HHCT) failed to achieve primary engraftment. An additional four patients who received TCD-HHCT experienced graft rejection (GR) soon after engraftment, although no patients who received non-TCD-HHCT experienced GR. All of the five patients who experienced early graft failure (GF) after TCD-HHCT received a second HHCT and achieved sustained engraftment. The patient who experienced GF after non-TCD-HHCT died of infection after the second HHCT from the same donor at D+54 from the first HHCT. Acute graft versus host disease (aGVHD) was assessed in 27 patients, excluding the six patients with early GF. Thirteen of the 27 patients developed grade II to IV aGVHD (8 grade II, 4 grade III and 1 grade IV) leading to a cumulative incidence of 48.1%. And five patients developed extensive chronic GVHD. Of the total of 33 patients, three patients (one with TCD-HHCT and two with non-TCD-HHCT) died of TRM. One patient died of severe autoimmune hemolytic anemia after a booster infusion of CD34+ cells for poor graft function at +457 days, one died of infection after salvage transplantation for GF at +54 days from his first HHCT, and one died of pulmonary complications at +236 days. At a median follow-up of 28 months (range, 4-99 months), the overall survival at 2 years was 90.1% (95% CI, 80.7-100%) and all 30 surviving patients were transfusion-independent. Our study suggests that HHCT with or without in vitro T cell depletion is a realistic therapeutic option for pediatric patients with SAA who lack a matched related or unrelated donor. Disclosures No relevant conflicts of interest to declare.

Impact of Hematopoietic Stem Cell (HSC) Recruitment and Graft Composition on Transplant Outcome after Reduced Intensity Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT): A Study of the Société Française de Greffe de Moelle Osseuse et de Thérapie Cellulaire (SFGM-TC) Registry.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1146-1146
Author(s):  
Thomas Prebet ◽  
Quoc-Hung Le ◽  
Jean-Michel Boiron ◽  
Didier Blaise ◽  
Anne Huynh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conditioning Regimen ◽  
Cell Number ◽  
Hematopoietic Stem ◽  
Transplant Outcome ◽  
Abo Incompatibility ◽  
Grade Ii ◽  
Graft Composition ◽  
Reduced Intensity

Abstract Evidence of an impact of graft product on transplant outcome after PBSCT is actually rising. Here, we investigated retrospectively the potential impact of HSC recruitment procedure (i.e. G-CSF stimulation schedule and apheresis number) and graft composition (CD34+ and CD3+ cell number) on transplant outcome (GVHD, OS, EFS). Our analysis concerned 488 HLA matched sibling allogeneic reduced intensity conditioning (RIC) PBSCT for hematological malignancies (116 MM, 110 AML, 109 NHL, 41 CLL, 41 MDS, 24 CML, 19 HD, 17 ALL and 11 MPS) reported on the SFGM-TC registry between 1998 and 2004. Follow-up was updated in April 2005. RIC-PBSCT was performed during first line treatment in 225 (49%) patients and a previous HSCT was recorded in 55% of the cases. Before RICT, 161 patients were in Complete Response, 161 in Partial Response, 34 in Stable Disease and 132 in Progressive Disease. Regarding donors, median age was 49 years, sex mismatching and ABO incompatibility were seen in 222 and 162 patients respectively. CMV status was positive either in donor or recipient in 152 cases. G-CSF median duration was 5 days (3–7days) at a median dose of 10μg/kg/day (4.6–16). G-CSF was given bid in 40% of the stimulations. Filgrastim was used in 59% of the donors and Lenograstim in 41% of the donors. A single apheresis was performed in 107 donors, 2 in 298 donors, more than 2 in 93 donors. The median number of CD34+ cells infused was 5.6x106 CD34+/kg (1–26) and the median CD3+ cells was 302x106 CD3+/kg (63–996). Conditioning regimen was most frequently an association of Fludarabine Busulfan and Anti Thymocyte Globuline (246 cases, duration of ATG 1 day: 18%, 2 days: 20%, 3 days: 20%, 4 days: 8% 5 days: 33%) or Fludarabine + TBI 2 Gy (123 patients). GVHD prophylaxis was a cyclosporine based treatment in 478 patients [95% of the cases (+ Methotrexate: 29%, + Mycophenolate Mofetil: 26%)]. Median follow-up after transplantation was 35 months (range: 0–86). Acute GVHD (grade II-IV) and cGVHD incidences were 35% (n=163 on 488 patients) and 50% (n=217 on 430 patients) respectively. The 3-year OS was 40% and the 3-year EFS was 34%. Treatment related mortality was 12% at 1 year and 15% at 3 years. In multivariate analysis studying pre and post transplant factors, a significant impact was shown of G-CSF duration (HR: 0.79 (0.62–1) p=0,05), G-CSF daily dose (HR: 1.13 (1–1.28) p=0,04) on OS. Other variables also influenced OS (NHL vs AML, aGVHD grade II vs 0-I and III-IV vs 0-I and cGVHD: yes vs no) and EFS (Sex mismatch, ABO incompatibility, NHL vs AML, FBS ATG duration: 5 days vs 2 days, aGVHD grade II vs 0-I and III-IV vs 0-I and cGVHD: yes vs no). No influence of graft composition or stem cell recruitment was demonstrated on aGVHD and cGVHD incidences although we found a significant impact of conditioning (FBS ATG 1 day vs 2days and 5days vs 2days). In conclusion, this study demonstrates that, surprisingly, graft composition has no impact on transplant outcome. Prolonged administration of moderate dose of G-CSF seems to be the best schedule for PBSC recruitment.

Updated Analysis of Allogeneic HSCT after RIC for Hematological Malignancies from the Société Française de Greffe de Moelle Osseuse et de Thérapie Cellulaire (SFGM-TC) Registry.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1085-1085
Author(s):  
Mauricette Michallet ◽  
Quoc-Hung Le ◽  
Mohamad Mohty ◽  
Franck E. Nicolini ◽  
Jean-Michel Boiron ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Term Survival ◽  
Allogeneic Hsct ◽  
Unrelated Donors ◽  
Grade Ii ◽  
Long Term Survivors

Abstract This report updates a retrospective study from SFGM-TC registry concerning 1108 patients who underwent allogeneic hematopoeitic stem cell transplantation (HSCT) after reduced intensity conditioning (RIC) from HLA identical siblings (84%) and unrelated donors (16%) for hematological malignancies. At time of conditioning, 442 patients were in CR, 337 in PR, 107 in stable disease (SD) and 222 in progressive disease (PD). As conditioning, 255 patients received fludarabine and TBI (2 grays), 465 patients fludarabine, busulfan and ATG and 388 patients an other regimen. After transplant, 336 patients (30%) developed an acute GVHD ≥ grade II (grade II: 178, III: 80 and IV: 78). A chronic GVHD was present in 388 patients (35%) (185 limited and 203 extensive). With a median follow-up of 30 months, the 3 and 5-year probability of overall survival (OS) were 43.5% (40–47) and 32%(29–35) respectively and the 3 and 5-year probability of event-free survival (EFS) were 35%(31–39) and 28% (24.5–31) respectively. The TRM at 1 year, 2 years and 3 years was 15% (13–17), 18% (15.5–21) and 20% (17–23). A mixture model, gfcure with Splus statistical package determined the percentages of long-term survivors and its adequacy was verified graphically. The probability to be a long-survivor was 24% (17.5–32.5) (Fig.1) and to be a long event-free survivor was 23% (19–28) (Fig. 2). The multivariate analysis has tested recipient and donor age, disease status pre-transplant, number of transplants before RICT, HSC source, sex matching, HLA matching, CMV status and ABO compatibility. The only factor which had a significant impact on long-term survival after RICT was the disease status just prior conditioning: PR versus CR: HR: 3.63 [1.14–9.18] p<0.001 and PD versus CR: HR: 4.35 [2.22–8.51] p<0.0001. In conclusion, these updated data demonstrate that allogeneic HSCT after RIC was able to possibly cure 23% of patients with haematological malignancies and the most important factor to take into account remains to be in CR pre-transplant. Figure 1 Figure 1. Figure 2 Figure 2.

Sign in / Sign up

Export Citation Format

Share Document