Long-Term Follow-Up of Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3032-3032
Author(s):  
John Kuruvilla ◽  
Qikun Bao ◽  
Mira Goldberg ◽  
Vikas Gupta ◽  
Thomas L. Kiss ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Small Sample ◽  
Unrelated Donor

Abstract Introduction Allogeneic stem cell transplantation (Allo-SCT) remains an option for patients with chronic lymphocytic lymphoma (CLL). Our program employs a strategy using allo-SCT for patients (pts) with high risk disease based on clinical characteristics and prior therapy. We performed a retrospective analysis to examine long-term disease control and treatment toxicity. Methods A total of 52 patients (pts) are included who underwent allo-SCT at our institution between Aug 1989 and Dec 2005. Patients were in a chemosensitive remission at the time of SCT. The conditioning regimen consisted of busulfan (1 mg/kg PO q6h X4 days between 1989–200 and 3.2 mg/kg IV daily X 4days subsequently) and cyclophosphamide 60 mg/kg X 2 days. Cyclophosphamide 60 mg/kg X 2 days and TBI 12 Gy was used for unrelated donor SCT. Reduced intensity conditioning (RIC) SCT were typically performed with Fludarabine 50 mg/m2 for 4 days and 2 Gy TBI. GVHD prophylaxis was with cyclosporine A and methotrexate. Results There were 34 males and 18 females. The median age at the time of transplant was 51 years (range 26 to 65). Histologic subtype was: CLL and/or small lymphocytic lymphoma (SLL); 48 and T-prolymphocytic leukemia (PLL): 4. The median number of prior chemotherapy regimens was 3 (range 1 – 10) and was unavailable in 16. Prior chemotherapies included: anthracycline-based: 24, prior purine analog: 32, prior platinum-based: 8, prior auto-SCT: 1, prior rituximab: 5. The median time from diagnosis to allo-SCT was 58 months (range 5 – 260). 10 pts underwent RIC SCT. Graft source was: matched sibling (MSD) bone marrow (BM): 18, MSD peripheral blood stem cells (PBSC): 20, Mismatch related (MMRD) bone marrow (BM): 1, MRD PBSC: 4, matched unrelated donor (MUD) BM: 8, MUD PBSC: 1. At 5 years, the overall survival of the entire cohort is 51% (95% confidence intervals: 34 – 68%) with two long-term survivors of 14 and 17 years. Treatment-related mortality (TRM) was 20 of 52 pts (38%). 4 pts have relapsed ((8% of total cohort) and non-relapse mortality was 1 pt (2%). Overall survival by intensity of SCT conditioning regimen was not significant (p=0.3). TRM was similar in pts who received fully myeloablative SCT (40% vs. 20% in RICSCT group, p=0.29). Conclusions Acceptable survival post-SCT is possible using an allo-SCT strategy in CLL. However, TRM remains high in this group of heavily pre-treated patients with a median age of over 50 that predominantly received fully myeloablative allo-SCT. Due to small sample size, the potential benefit of reduced TRM with RICSCT cannot be demonstrated. Ideally, allo-SCT should be considered earlier in the course of the disease based on risk stratification utilizing traditional risk factors and modern prognostic factors such as FISH studies and novel markers.

Psychosocial and Behavioral Issues in Stem Cell Transplantation

2006 ◽  
Author(s):  
Sean Phipps
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Well Being ◽  
Unrelated Donor ◽  
Behavioral Issues ◽  
Leukemic Relapse

Stem cell transplantation (SCT) or bone marrow transplantation (BMT) has evolved from a heroic, experimental therapy of last resort to a standard therapy for many high-risk leukemias and the preferred first option after leukemic relapse (Sanders, 1997; Santos, 2000; Treleaven & Barrett, 1998; Wingard, 1997). The indications for SCT have widened to include a number of other malignant disorders, including lymphomas, solid tumors, and even brain tumors, as well as to a growing number of nonmalignant disorders (Meller & Pinkerton, 1998; Santos, 2000; Treleaven & Barrett, 1998). The growth of bone marrow registries that allow for wider use of unrelated donor transplants and developments in stem cell selection techniques that allow for haplotype transplants using mismatched family donors, including parents, have greatly increased the availability of SCT as a viable treatment option for seriously ill children (Mehta & Powles, 2000). At the same time, advances in supportive care have led to improved survival outcomes and thus to a rapidly growing number of long-term survivors of SCT (Santos, 2000; Treleaven & Barrett, 1998). Yet, despite the extraordinary medical and technical advances that have saved the lives of many children, SCT remains a high-risk medical procedure involving a prolonged and physically demanding treatment regimen that can challenge the coping capacities of patients and their families. Psychosocial research in pediatric SCT has progressed more slowly, but available studies indicate that SCT is a stressful experience that can have a negative impact on the social functioning, self-esteem, and general emotional well-being of survivors (Barrera, Pringle, Sumbler, & Saunders, 2000; McConville et al., 1990; Parsons, Barlow, Levy, Supran, & Kaplan, 1999; Phipps, Brenner, et al., 1995; Phipps & Barclay, 1996; Rodrigue, Graham-Pole, Kury, Kubar, & Hoffman, 1995; Stuber, Nader, Yasuda, Pynoos, & Cohen, 1991; Vannatta, Zeller, Noll, & Koontz, 1998). A number of studies have also focused on parental response to SCT (Barrera et al., 2000; Kronenberger et al., 1998; Manne et al., 2001, 2002; Phipps, Dunavant, Lensing, & Rai, 2004; Rodrigue et al., 1996; Streisand, Rodrigue, Houck, Graham-Pole, & Berlant, 2000). Much of the literature to date has focused on long-term outcomes in survivors, particularly neurocognitive and academic outcomes.

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.

Stem Cell Transplantation for Relapsed and Refractory Burkitt Lymphoma.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4589-4589
Author(s):  
Steven Kwon ◽  
Amir Steinberg ◽  
Catherine Bresee ◽  
Mercedes Franco ◽  
Angela M. Lopez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Burkitt Lymphoma ◽  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Small Sample ◽  
Refractory Disease ◽  
Hematopoietic Stem

Abstract Abstract 4589 Background: Burkitt lymphoma is a highly aggressive and rapidly proliferating hematologic malignancy. Various chemotherapy regimens (HyperCVAD, CODOX-M/IVAC, REPOCH) have been shown to improve overall survival rate. However, in instances of relapsed or refractory disease, there is no clear-cut standard of care. Hematopoietic stem cell transplantation (HCT) has shown benefit in these patients. Here, we report our institutional experience using HCT for relapsed/refractory Burkitt lymphoma. Methods: Between February 1994 and January 2010, 13 patients (10 males, 3 females) with refractory or relapsed Burkitt lymphoma were retrospectively evaluated. The patients in question were administered a particular conditioning regimen followed by stem cell transplantation (11 autologous, 2 allogeneic). The average age at transplant was 41.8± 3.4 years (range 24 to 67). Stem cell source was from peripheral blood in all transplants including allogeneic (2 HLA-identical sibling transplants). The conditioning regimens for HCT consisted of the following: TBI/Rituximab/Cytoxan/VP16, TBI/Cytoxan/VP16, BEAM, Cranial Spinal boost/TBI/Cytoxan/VP16 or Cranial boost/TBI/Cytoxan. Results: On average, patients received transplant 299 ± 36 days after initial diagnosis (range 153 to 582). All patients achieved engraftment. For the 5/13 deceased patients (38%), cause of death was attributed to relapsed/refractory disease (n=2) and treatment related causes (n=3). Using the Kaplan-Meier method, the average survival time after transplant was computed at 27.7 ± 5.3 months and 75% were alive 2-years after transplant. Likely due in part to the small sample size, no covariates (age, gender, conditioning regimen, HIV status, presence of B symptoms, and CNS or bone marrow involvement) were found to be predictive of survival rates. Conclusion: Patients with Burkitt lymphoma, known for its rapid growth, can achieve long-term complete remission (CR) with intense, combination chemotherapy. Despite successful long-term remission rates, a substantial portion of patients die from uncontrolled disease. At the first sign of refractory or relapsed disease, resources should be mobilized to proceed with HCT. Our study, though limited in size, provides further compelling evidence that long-term CR, and potentially cure, may be achieved using HCT as a treatment modality. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation For Patients With Adrenoleukodystrophy. Nationwide Retrospective Study In Japan

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2148-2148
Author(s):  
Koji Kato ◽  
Hiromasa Yabe ◽  
Shunichi Kato ◽  
Souichi Adachi ◽  
Yoshiko Hashii ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Low Dose ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Transplant Outcome

Abstract Introduction Adrenoleukodystrophy (ALD) is an autosomal recessive disorder with progressive neurodegeneration caused by the mutation of ABCD1 gene and allogeneic stem cell transplantation (SCT) at its early stage is recognized as the only effective treatment modality to control the neurological symptoms. But the transplant outcome according to the conditioning regimen is not well understood so far. Here we analyzed the transplant outcome of patients with ALD using the clinical data accumulated in the Japan Society of Hematopoietic Cell Transplantation and tried to find the favorable conditioning regimen. Methods From 1988 to 2010, 76 patients with ALD were transplanted and their age at transplant was 1-34 years old (median 8). Stem cell sources the patients received were bone marrow (sibling 26, non-sibling related donor 5, unrelated volunteer donor 17), and cord blood (sibling 1, unrelated 28). Conditioning regimen was classified into four categories of A: busulfan + cyclophosphamide +/- others, (n=25), B: melphalan + total lymphoid irradiation (TLI) / thoraco-abdominal irradiation (TAI) +/- fludarabine +/- anti-thymocyte globulin (n=23), C: fludarabine + melphalan +low dose total body irradiation (TBI) (n=18), and D: others (n=10). Results Sustained engraftment was obtained in 59 patients (77.8%) and it was significantly higher in bone marrow transplant (BMT) patients than cord blood transplant (CBT) patients (87.8% vs 60.7%, P=0.001). The incidence of acute graft-versus-host disease (GVHD), chronic GVHD and treatment related mortality of all patients were 7.9%, 19.3%, and 11.9%, respectively. Ten year overall survival (OS) and event free survival (EFS) of all patients were 83.7% and 64.1%, respectively. Ten patients died of either disease progression (n=2), or transplant related complications (n=8). Five year OS and EFS according to the conditioning regimen was A: 91.6% and 75.8%, B: 85.7% and 60.9%, C: 100% and 83.3%, D: 77.8% and 48.0%, respectively and they were not significant (P=0.379 in OS and P=0.183 in EFS, respectively). TBI was given to 22 patients with median dose of 4Gy (range 2-10.2) and sustained engraftment was obtained in 19 patients and all of 22 patients are alive. In patients who were not given TBI (n=54), 41 patients obtained engraftment and 44 patients are alive. OS according to presence or absence of TBI was 100% with TBI (n=22) and 86.1% without TBI (n=54) (P=0.091). By multivariate analysis for EFS, BMT and TBI were identified as good prognostic factors compared to CBT or non-TBI (HR 3.303, P=0.005, and HR 3.257, P=0.038, respectively), but OS of CBT was improved after 2005 compared to before 2004 (94.7% vs 68.6%, P=0.090). Conclusion Our results showed that conditioning regimen which includes TBI, even at low dose could provide better transplant outcome and the result of CBT improved after 2005 even though it was proved to be a significantly poor risk factor in the analysis of entire cohort. CBT enables urgent SCT when family donor is not available, and immediate transplant is essential for patients with ALD because of its nature. More precise assessment with brain MRI and neuropsychological examination is mandatory to evaluate the transplant outcomes of patients with ALD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Reduced Intensity Vs. Myeloablative Conditioning Followed By Allogeneic Stem Cell Transplantation for Patients with Myelodysplastic Syndrome: Long Term Follow-up of a Prospective Randomized EBMT Phase III Study (RICMAC-Trial)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1019-1019
Author(s):  
Nicolaus Kroeger ◽  
Simona Iacobelli ◽  
Linda Koster ◽  
Dietger Niederwieser ◽  
Uwe Platzbecker ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Phase Iii ◽  
Long Term Follow Up

Abstract Introduction Retrospective studies in MDS/sAML suggest that reducing the intensity of the conditioning regimen prior to allogeneic stem cell transplantation reduces the risk of non-relapse mortality but is associated with a higher risk of relapse. A higher risk of relapse after RIC was confirmed in a prospective BMT CTN study but the prospective randomized studies from the EBMT for MDS and sAML did not show a difference in outcome after 2 years (J Clin Oncol. 2017 Jul 1;35(19):2157-2164). Here we present a long term follow-up of the study after a median follow-up of 75 months (range 4-150 months). Methods Within the European Society of Blood and Marrow Transplantation (EBMT) we conducted a prospective, multicenter, open label, randomized phase III trial comparing comparing a busulfan based (Busulfan 8mg/kg orally or equivalent dosis intravenously (iv) plus fludarabin 180mg/m²) reduced intensity conditioning regimen (RIC) and a standard myeloablative busulfan (Busulfan 16mg/kg orally or equivalent dosis iv plus cyclophosphamide 120mg/kg) based regimen (MAC) in patients with MDS or sAML (<20 % blasts). Between May 2004 and December 2012, a total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1 : 1 ratio and stratified according to donor, age and blast count. Results In the first report (JCO 2017) the CI of NRM after 1 year was 17% (95% CI 8-26%) after RIC and 25% (95% CI 15-36%) after MAC (p = 0.29). The CI of relapse at 2 years was 17% (95% CI 8-26%) after RIC and 15% (95% CI 6-24%) after MAC (p = 0.6), resulting in a 2 year relapse-free and overall survival of 62% (95% CI 50-74%) and 76% (95% CI 66-87%) after RIC and 58% (95% CI 46-71%) and 63% (95% CI 51-75%) after MAC (p = 0.58 and p = 0.08, respectively). In the current follow-up study, all cases but one who were alive at last report could be updated. The median follow-up is now 75 months in the MAC and 72 months in the RIC arm. Since last follow-up =18 death occurred in both arm (MAC n=8, RIC n=10) 8 relapses (MAC n=4; RIC n=4) and 6 NRM (MAC n=2; RIC n=4). Second allogeneic stem cell transplantation was performed in 18 patients (n=10 in RIC and n=8 in MAC) due to graft failure (n=4) relapse (n=11) and others (n=3). The CI of chronic GvHD at 5 years was 65% (95% CI: 53-78) after RIC and 68% after MAC ((95% CI: 55-81; p = 0.70). At 5 years there was no difference in CI of NRM (22%, 95%CI: 12-32 vs 30% , 95%CI : 19-42, p=0.5) in CI of Relapse (22% , 95% CI: 12-32 vs18%, 95% CI: 8-28, p= 0.7), Relapse free- (57%, 95% CI: 44-69 vs51%, 95% CI: 39-64, p=0.8) and Overall survival (69%, 95% CI: 58-80 vs 53%, 95% CI: 40-65, p=0.15) between RIC and MAC, respectively. Conclusion This long term follow-up of the prospective randomized EBMT trial confirmed early results that RIC resulted in at least similar long term relapse-free and overall survival as MAC in patients with MDS or sAML. The trial was registered under ClinicalTrials.gov Identifier: NCT01203228. Disclosures Niederwieser: Miltenyi: Speakers Bureau; Novartis: Research Funding. Platzbecker:Celgene: Research Funding. Scheid:Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria. Stelljes:MSD: Consultancy; Amgen: Honoraria; JAZZ: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Honoraria. Heim:Novartis: Research Funding. Bethge:Miltenyi Biotec GmbH: Consultancy, Honoraria, Research Funding; Neovii GmbH: Honoraria, Research Funding. Kobbe:Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Other: Travel Support, Research Funding.

Unrelated Allogeneic Stem Cell Transplantation with Myeloablative Preparative Regimen for Adult Patients with Acute Lymphoblastic Leukemia in CR: A Survey from the European Group for Blood and Marrow Transplantation (EBMT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3112-3112
Author(s):  
Nadezda Basara ◽  
Myriam Labopin ◽  
Tapani Ruutu ◽  
Axel Zander ◽  
Renate Arnold ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
Marrow Graft

Abstract Data from the EBMT indicate that approximately 46% of Unrelated Allogeneic Stem Cell Transplantation (UD-SCT) in Europe utilize peripheral blood (PB) and 54% bone marrow (BM) as a graft source for adult patients with ALL since January 1998. However, prospective randomized trials comparing the two stem cell sources are lacking. This study describes the results of 782 adult patients with ALL in remission (422 BM and 360 PB) transplanted in different centers affiliated with the EBMT from 1998 to 2004 with an HLA identical unrelated donor (HLA-A and -B low resolution and HLA-DRB1 allelic typing). Median age was 27 years for BM (range 16–63, male 60%) and 30 years for PB (range16–63, male 62%), respectively. Fifty four (54%) and 64% of patients were transplanted in first complete remission (CR1) in the BM and PB groups, respectively. The frequency of female donor to male recipient was 18% in the BM and 15% in the PB group. Total Body Irradiation (TBI)-based preparative regimens were given in 85% and 88% of patients in the BM and PB group respectively. Graft-versus-Host Disease (GvHD) prophylaxis consisted of cyclosporine A (CsA) (6% and 4%), CsA and methotrexate (77% and 58%) or in vitroT-cell depletion (17% and 38% in BM and PB group, respectively). With the median follow-up of 17 (range 1–92) and 11,3 (range 1–71) months, the incidence of GvHD grade II–IV was 37% in the BM group and 39% in the PB group (p=0.39). Probabilities of LFS, TRM and relapse were calculated using the Kaplan-Meier estimate. LFS was 45+/−3% vs 36+/−3% (p=0.04) transplant related mortality (TRM) was 33+/−2% and 39+/−3(p=0.29 while incidence of relapse was 32+/−3% and 41+/−4%(p=0.06), in the BM and PB groups respectively. Two years leukemia-free survival (LFS) for the patients transplanted in CR1 was 48% (BM) and 42% (PB, p=0.48). However, 2-years LFS for patients transplanted in CR2 or CR3 was significantly higher in the BM compared to the PB group (42% and 26%, p<0.004). The probability of relapse was significantly lower in BM compared to PB (32% vs 54%, p<0.001) without there being a detectable difference in TRM at 2 years (38% vs 43%, p= 0.31). In conclusion, the results of this retrospective comparative study confirm that UD-SCT with BM and PB as a graft source have similar results for patients in CR1. However, patients transplanted in CR2 or CR3 with a bone marrow graft, have decreased relapse incidence and better LFS, probably reflecting disease and transplant related differences compared to PB transplants such as in vitro T cell depletion more used in those transplants.

High Incidence of BK-Virus-Related Hemorrhagic Cystitis after Busulfan/Fludarabine Myeloablative Conditioning in Allogeneic Stem Cell Transplantation Recipients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5254-5254
Author(s):  
Gorgun Akpek ◽  
Ashraf Badros ◽  
Aaron P. Rapoport ◽  
Kathleen Ruehle ◽  
Kristen Barton ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Hemorrhagic Cystitis ◽  
Conditioning Regimen ◽  
Bk Virus ◽  
Unrelated Donor ◽  
Myeloablative Conditioning ◽  
High Incidence

Abstract Busulfan (BU) and Fludarabine (F) has been reported by de Lima et al. to be a well-tolerated myeloablative conditioning regimen with 3% incidence of hemorrhagic cystitis (Blood2004;104:857). Between 5/2005 and 5/2006, we performed allogeneic stem cell transplantation (SCT) in 29 patients following BU+F (n=17) and other (n=12) myeloablative regimens. Nineteen (66%) patients were in remission and 10 (34%) had active disease at BMT. Twenty patients had AML, 4 ALL and 5 had other malignancies. Busulfan was given at 130mg/M2 over 3 hours on 4 successive days, along with Fludarabine 40mg/M2 on 4 successive days. Eighteen (72%) had matched-related 7 (24%) had matched-unrelated donor (MUD) transplant. GVHD prophylaxis consisted of Tacrolimus and low-dose Methotrexate. Thymoglobulin (n=4) and CAMPATH (n=3) were given along with conditioning in MUD/one-antigen mismatch transplant recipients (5 BU+F and 2 other). As of August 1st, 2006, 19 (65%) patients are alive. Of 26 evaluable patients, the incidence of bacterial (59% vs. 89%), fungal (29% vs. 11%) infections were similar between Bu+F and other group, respectively. CMV reactivation was observed in 78% in other group as compared to 35% in BU+F recipients (p=0.09). Hemorrhagic cystitis (HC) occurred in 6 patients (35%) in BU+F group and in 1 (11%) patient in other group (p=0.35). BK virus was detected by quantitative PCR in all patients with HC. Two BK(+) cases were in BU+F+CAMPATH group. Considering 18 AML patients who received transplant in remission and had at least 2 months of follow-up, 5 patients (38%) in BU+F group relapsed within 6 months of transplant. Two out of 5 patients relapsed in the other group. Our findings suggest that BU+F myeloablative conditioning appears to be associated with high incidence of BK-related hemorrhagic cystitis and may have long-term consequences. Further studies are warranted.

Favourable Overall Survival with Myeloablative Allogeneic Stem Cell Transplantation for Follicular Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3005-3005
Author(s):  
John Kuruvilla ◽  
Qikun Bao ◽  
Erica Messner ◽  
Vikas Gupta ◽  
Thomas L. Kiss ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Disease Control ◽  
Allogeneic Stem Cell Transplantation ◽  
Unrelated Donor ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Introduction Allogeneic stem cell transplantation (Allo-SCT) remains an option for patients with follicular lymphoma (FL). Our program employs a strategy using allo-SCT for patients (pts) with high risk disease based on clinical characteristics. We performed a retrospective analysis to examine long-term disease control and treatment-related mortality. Methods 41 pts with indolent FL (follicular small cleaved [FSC], follicular mixed [FM] or FL grade 1,2 by WHO criteria) underwent allo-SCT at our institution between Jan 1989 and Dec 2005. Patients were in a chemosensitive remission at the time of SCT. The conditioning regimen consisted of busulfan (1 mg/kg PO q6h X4 days between 1989–200 and 3.2 mg/kg IV daily X 4days subsequently) and cyclophosphamide 60 mg/kg X 2 days. Cyclophosphamide 60 mg/kg X 2 days and TBI 12 Gy was used for unrelated donor SCT. GVHD prophylaxis was with cyclosporine A and methotrexate. Results There were 21 males and 20 females. The median age at the time of transplant was 45 years (range 24 to 58). Histologic subtype was: unclassified indolent FL: 3, Grade 1 or FSC: 17, Grade 2 or FM: 21. The median number of prior chemotherapy regimens was 2 (range 1 – 6) and was unavailable in 5. Prior anthracycline: 37, prior purine analog: 9, prior platinum-based: 20, prior auto-SCT: 1, prior rituximab: 11. The median time from diagnosis to allo-SCT was 23 months (range 6 – 161). 38 pts received BuCy conditioning. 2 patients underwent RIC SCT. Graft source was: matched related (MRD) bone marrow (BM): 28, MRD peripheral blood stem cells (PBSC): 4, Mismatch related (MMRD) bone marrow (BM): 1, MMRD PBSC: 2, matched unrelated donor (MUD) BM: 1, MUD PBSC: 1, and syngeneic BM: 4. The five year overall survival is 77% (95% confidence intervals 73 – 91%) with a median follow-up of 48 months post-SCT. Treatment-related mortality was 5 of 41 pts (12%). Non-relapse mortality was seen in one patient (3%). One patient has relapsed at over 3 years post-SCT while all recipients of syngeneic SCT remain in remission. Conclusions These results demonstrate that in selected patients, a fully myeloablative allo-SCT utilizing Busulfan-Cyclophosphamide conditioning provides excellent overall survival and disease control with low TRM. Prospective comparisons of RICSCT with myeloablative SCT should be performed in order to better evaluate these strategies.

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

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 617-617 ◽  
Author(s):  
Jean-Hugues Dalle ◽  
Luc Caty ◽  
Regis Peffault ◽  
Alexandra Salmon ◽  
Valerie Mialou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Hematopoietic Stem

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

Gemcitabine, Fludarabine, and Melphalan (G-FM) as Reduced-Intensity Conditioning (RIC) Regimen for Allogeneic Stem Cell Transplantation (Allo-SCT) in Relapsed and Refractory Hodgkin Lymphoma (HL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3003-3003
Author(s):  
Paolo Anderlini ◽  
Rima M Saliba ◽  
Celina Ledesma ◽  
Christina M Chancoco ◽  
Sandra Acholonu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Pulmonary Toxicity ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Cutaneous Toxicity ◽  
Platelet Recovery ◽  
Grade 3

Abstract Abstract 3003FN2 Objective: Progressive disease (PD) remains the main cause of treatment failure following RIC allo-SCT in HL (Peggs KS et al, BJH 2008: 143; 468). We elected to explore the feasibility of adding gemcitabine (G), a highly active agent in relapsed/refractory HL (Santoro A et al, JCO 2000 :18; 2615), to our standard fludarabine (F) - melphalan (M) RIC in patients with relapsed and refractory HL undergoing allo-SCT, with the ultimate goal to augment cytoreduction and reduce the incidence of PD. Main G-associated non-hematologic toxicities include pulmonary, skin toxicities and mucositis. Patients and Methods: Between 8/07 and 3/11, fifteen consecutive HL patients (Unique Patient Number/UPNs 1–15) underwent an allo-SCT with the G-FM regimen. They had failed multiple conventional treatments (median prior chemotherapy regimens: 4; range 2–9), radiation therapy (6/15) and a prior auto-SCT (7/15). The median age was 33 years (range 20–46). Disease status at SCT was chemosensitive relapse (n=4), untreated relapse (n=1), induction failure chemosensitive (n=2), complete remission undetermined (CRU1 and CRU2) (n=8). The median time to PD after auto-SCT was 10 months (range 3–19). The donor was an HLA-identical sibling (n=10) or matched unrelated donor (MUD; n=5, with UPN 6 having a 9/10 match). The conditioning regimen was G 800 mg/m sq IV x1 at day -7 (two patients, UPN 6 and UPN 7 received G 1000 mg/m sq IV x2, day -5 and day -2 as part of a dose escalation attempt stopped for excess toxicity), F (32 mg/m sq IV x4, day -5 to day -2), M (70 mg/m sq IV x2, day -3 and day -2; total dose 140 mg/m sq). Thymoglobulin (4 mg/kg IV) was added in MUD allografts. Graft-vs-host disease (GVHD) prophylaxis included tacrolimus and mini-dose methotrexate (5 mg/m sq). Results: Myeloid recovery was prompt, with an absolute neutrophil count (ANC)>500/mcL at day +12 (range 11–20). Median platelet recovery at 20K/mcL was at day +14 (range 9–26). Chimerism studies indicate 100% donor-derived engraftment in 13/13 evaluable patients (100%). Day 100/overall transplant-related mortality (TRM) were 2/15 (13%) and 2/15 (13%), respectively. Acute GVHD (grade II-IV) occurred in 8/14 evaluable patients, chronic GVHD in 7/13 evaluable patients (extensive in 7). Pulmonary toxicity was seen in four patients (26%). Grade 4 pulmonary toxicity was seen in UPN 6. Otherwise it was grade 1–2 (n=3). Cutaneous toxicity (skin rash, responsive to steroid therapy) was seen in five patients (33%: grade 3 n=1; grade 1–2 n=4). Mucositis was seen in nine patients (60%). It was grade 3 (n=1); grade 1–2 (n=8). Other organ toxicities were not seemingly markedly different from the ones seen with FM140 only. Three patients expired (graft rejection n=1, in UPN 6; CMV pneumonia n=1; PD n=1). Twelve patients are alive (ten progression-free, eleven in CR/CRU) with a median follow-up of 18 months (range 2–33). Actuarial rates of overall survival (OS) and progression-free survival (PFS) at 24 months are 87% (95% CI: 56–96) and 49% (95% CI: 18–74), respectively (see Figure). While a formal comparison with our historical experience with the FM140 regimen is clearly not possible, OS and PFS (actuarial estimates) at 24 months were 64% (95% CI: 49–76), and 32% (95% CI: 20–45), respectively (Anderlini et al, Haematol 2008; 93 :257). Conclusions: The addition of G to FM140 is feasible. Pulmonary, cutaneous toxicities, as well as mucositis, while clinically significant, were manageable and did not contribute to mortality in the patients treated with only one G dose. While quite encouraging, these data remain preliminary. The G-FM regimen deserves further study in a larger cohort of patients. Disclosures: Off Label Use: Gemcitabine, fludarabine and melphalan as part of conditioning regimen for allogeneic stem cell transplantation.

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