Outcome of Sibling Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantations in Low-Grade B Cell Lymphoproliferative Disorders. A Single Centre Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5059-5059
Author(s):  
Ronan Desmond ◽  
Marianna David ◽  
Eibhlin Conneally ◽  
Paul Browne ◽  
Mairead Ni Conghaile ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Chronic Gvhd ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Lymphoproliferative Disorders ◽  
Mixed Chimerism ◽  
Low Grade ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity

Abstract Reduced intensity conditioning allogeneic stem cell transplantations (allo-SCT) have been developed to exploit graft-versus-malignancy effect while reducing the toxicity of allo-SCT. We report the outcome of 21 patients with low-grade B cell lymphoproliferative disorders transplanted in a single center. The mean age of the patients was 54 years (range 32–66) with 11 males, 10 females. Follicular lymphoma was the diagnosis in 10 patients, CLL in 5, mantle cell lymphoma in 4, MALT lymphoma in 1 and lymphoplasmocytoid lymphoma in 1 patient. The median number of prior treatment lines was 2. All patients received peripheral blood stem cell transplants from sibling donors and no patients had undergone a prior autologous SCT. 12/21 patients (57%) received a ATG based conditioning regimen while the remainder, 9/21 (42%) received a Campath containing conditioning regimen. Full donor chimerism was confirmed in 17/19 (89%) patients. Acute graft versus host disease (GVHD) developed in 5/21 (23%) of the patients. Chronic GVHD occurred in 7/21 (33%) with 5/21 occuring post donor lymphocyte infusion (DLI). DLI has been administered in 11/21 patients (52%), 2 for progressive disease and 9 for re-emerging mixed chimerism. Non-relapse mortality (NRM) at 100 days and 1 year were 5% and 12.5% respectively. With a median follow up of 21 months (range 3–54) the overall survival rates (OS) at 1 year and 2 years were 72% and 58% respectively. Progression free survival (PFS) at 1 year and 2 years were 66% and 50%. We have shown that reduced intensity conditioning allogeneic stem cell transplantation is associated with a low TRM comparible to that of autologous transplantation and allows long term control of low grade B-cell lymphoproliferative disorders.

Impact of Dendritic Cell CD16+ Recovery on Outcome after Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1409-1409
Author(s):  
Carme Talarn ◽  
Alvaro Urbano-Ispizua ◽  
Rodrigo Martino ◽  
Montse Batlle ◽  
Concha Herrera ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Critical Role ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Poor Prognostic Factor ◽  
Reduced Intensity

Abstract Dendritic cells (DCs) play a critical role in the regulation of alloimmune responses. Therefore, the number and function of these cells after allogeneic stem cell transplantation (allo-SCT) might influence patients’ outcome, an aspect scarcely investigated, particularly in the setting of reduced-intensity conditioning transplants (allo-RIC). Against this background, we studied DCs recovery in 92 patients (median age 50, range 17–67; male 57%), undergoing allo-RIC from HLA identical donors in five Spanish institutions between October 2002 and December 2004. Median follow up was 250 days (range, 25–708). Conditioning regimen consisted on fludarabine 150 mg/m2 + melphalan 140 mg/m2 for lymphoid malignancies (n=54), and fludarabine 150 mg/m2 + busulphan 10 mg/kg for myeloid malignancies (n=38); 71 (90%) patients had advanced disease. Peripheral blood samples were obtained at 1, 3, 6 and 12 months after transplant. DCs were identified as positive for HLA-DR and negative for lineage markers (CD3, CD14, CD19, and CD56). The expression of CD33, CD123 and CD16 was used to identify DC1, DC2 and DC CD16+ subsets, respectively; the immunophenotypic analysis being centralized at a single institution. The most significant association with clinical outcome was found with DC CD16+ levels at three months after transplantantation. Thus, at that time point, patients with a DC CD16+ count lower than the median (<1.5×104/mL) had a significantly higher incidence of relapse (59% vs. 45%; p=0.04), more transplant related mortality (30% vs. 0%; p=0.01), worse event free survival (EFS) (24% vs. 51%; p=0.002) and overall survival (0% vs. 55%; p=0.002). Only two factors were associated with worse EFS in the multivariate analysis: autologous transplantation before allo-RIC (RR 6.5, 95%CI 1.6–26.2; p=0.008), and DC CD16+ count lower than the median at +3m (RR 13.1; 95% CI 1.7–100.5; p=0.01). In conclusion, this study shows that besides a well-known poor prognostic factor (i.e., prior autologous transplantation) a low DC CD16+ count at three months after allo-RIC is associated with a poorer outcome, this probably reflecting impaired immunosurveillance mechanisms.

Long Term Results of Fludarabine/Melphalan as Reduced Intensity Conditioning Regimen (RIC) for Transplantation in Mantle Cell Lymphoma (MCL): Age Matters

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4388-4388
Author(s):  
Jorge Gayoso ◽  
Rodrigo Martino ◽  
Pascual Balsalobre ◽  
Javier De la Serna ◽  
José Francisco Tomás ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Long Term Results ◽  
Mixed Chimerism ◽  
Reduced Intensity Conditioning ◽  
Who Grade ◽  
Reduced Intensity

Abstract Introduction: Myeloablative allogeneic stem cell transplantation in patients (pts) with MCL has been traditionally used only in young pts without co-morbidities due to its high toxicity. During the last 10 years, many different reduced intensity conditioning (RIC) regimens have been introduced into clinical practice trying to reduce this toxicity, preserving the establishment of a meaningful graft-tumor effect (GVT). However, few homogeneus pts series have been reported focused on MCL, with encouraging results in some studies. Thus, we report herein the outcome of 18 consecutive MCL pts who received an allo-PBSC-RIC from an HLA-identical sibling donor with a long follow-up. Patients and methods: The RIC consisted in iv fludarabine 125–150 mg/m2 from day-8 to -4 and iv melphalan 80 or 140 mg/m2 on day-3 to -2. Rituximab 375 mg/m2 was added to RIC in 8 pts on days-9, +1, +8 and +15. GVHD prophylaxis consisted in standard cyclosporine and methotrexathe. Gradual cyclosporine tappering from day +50 was initiated if mixed chimerism or persistent disease were present. We focus on engraftment kinetics, early toxicities, non-relapse mortality (NRM), chimerism kinetics, GVHD as well as estimated anti-tumoral efficacy, progression-free and overall survival (PFS and OS). Results: 18 MCL pts were included from 2000 to 2008, with a median follow-up of 50 months. Median age was 56 years (range: 43–68), 13 were males, with a median pre-RIC treatment lines of 2 (1–4) including 2 autoHSCT. Before alloRIC, 13 pts (72%) were in 1st or later CR, while 5 pts (28%) were in chemo-sensitive PR. Median CD34+/kg infused cells were 5,8 ×106 (4,3–10,8) and 2,0 ×108 (0,7–4,1) CD3+ lymphocytes/kg. All pts engrafted, reaching ANC>500 on day +16 (13–20) and platelets>20.000 on day +12 (8–32), with no graft failures. Early toxicity (<day +100) included WHO grade 3–4 mucositis in 8 (44%), febrile neutropenia in 6 (33%) and bacterial infections in 4 (22%) with 2 deaths (1 varicella-zoster encephalitis and 1 refractory acute GVHD). There were 2 other deaths during the 1st year, both due to infections in the setting of extensive chronic GVHD, for a 1-year NRM of 22%. Complete donor T-cell chimerism (CC) was present at day +30 in 71% of evaluated pts and in 100% pts at day +90. Acute grade II–IV GVHD ocurred in 39% of pts at risk, with 17% of grade III–IV. Chronic GVHD affected 12/16 pts (75%), wich was extensive in 6 (38%). Only 1 patient (trasplanted in PR after 2 treatment lines) relapsed (6%). The 5-year estimated PFS and OS were both 77% (CI95%=58–97%) and 14 pts remain alive in CR. The only apparent prognostic factor in our study is age: 8 pts aged 60 or older have an OS of 33,3% vs 100% for the 10 pts younger than 60 years (p<0.001). Conclusions: AlloRIC with fludarabine and melphalan in MCL pts offers a good toxicity profile, with high engraftment rate and good long term disease-free survival, especially in pts younger than 60. The very low long-term relapse rate seen in the context of a high incidence of chronic GVHD supports the continued sensitivity of MCL to a GVT effect. Figure Figure

Reduced Intensity Conditioning Regimen for Allografting Following Autografting Is Feasible and Has a Strong Anti Multiple Myeloma Activity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5130-5130
Author(s):  
A.M. Carella ◽  
Germana Beltrami ◽  
Maria T. Corsetti ◽  
Potito Scalzulli ◽  
Nicola Cascavilla ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progressive Disease ◽  
Chronic Gvhd ◽  
Intensive Therapy ◽  
Conditioning Regimen ◽  
Mixed Chimerism ◽  
Reduced Intensity Conditioning ◽  
Conditioning Regimens ◽  
Age Range ◽  
Reduced Intensity

Abstract The development of reduced intensity conditioning regimens (RICT) has renewed interest in allografting for patients with multiple myeloma (MM). Taking advantage of this new approach, we firstly postulated that combining maximal tumor reduction achieved with autografting and the benefits of RICT, we could achieve more cures of multiple myeloma (MM) with acceptable toxicity. Sixteen patients, 51 years of age (range, 36–63) with previously treated stage III MM were given melphalan 140 mg/m2 and autologous peripheral blood progenitor cells (PBPC) reinfusion. The regimen-related toxicities were moderate with a median of 8 and 11 days of neutropenia and thrombocitopenia, respectively. Forty-six to 156 days later (median, 79 days), the patients received fludarabine 30 mg/m2/d x 3 days plus 2 Gy TBI and HLA-identical donor mobilized PBPC. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. Donor lymphocyte infusions were given to eight patients with stable mixed chimerism or progressive disease who did not show signs of aGVHD. Engraftment occurred in 14 patients (87%). Ten patients (62%) are alive with 9 of them in continuous complete remission 11–36 months (median, 30 months) after transplants. All remitters patients achieved full chimerism and developed GVHD. Grade II–III acute GVHD occurred in 7 patients (43%) but no patient died of aGVHD. Three patients (18%) developed extensive chronic GVHD requiring intensive therapy. Six patients died; five of them of progressive disease and one of progressive disease combined with extensive cGVHD and interstitial pneumonitis. In conclusion, this 2-step approach is feasible and demonstrated to have a strong antimyeloma activity with reduced deaths due to acute toxicities.

Favorable Outcomes with Acceptable Toxicity Using a Reduced Intensity Conditioning Regimen for Patients Otherwise Ineligible for Related Donor Allogeneic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5137-5137
Author(s):  
Peter Westervelt ◽  
Wendy Holmes ◽  
Robert Emmons ◽  
Pamela Becker ◽  
Phil Lowry ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity Conditioning Regimen ◽  
Reduced Intensity

Abstract Allogeneic stem cell transplantation represents a potentially curative treatment modality for patients with advanced hematologic malignancies. However, the toxicity associated with fully myeloablative conditioning regimens has historically limited its use to younger, otherwise healthy patients. To investigate the feasibility of allogeneic stem cell transplantation in older (over 55 years) or otherwise higher risk patients (eg, prior transplant) with fully HLA-matched sibling donors, a reduced intensity conditioning regimen consisting of fludarabine (30 mg/M2 IV qd X 6, day −8 to −3), ATGAM 10 mg/kg IV qod X 4, day −7/−5/−3/−1) and melphalan (100 mg/M2 IV X 1, day −2) was employed in a single institution setting. GVHD prophylaxis consisted of cyclosporine (2 mg/kg IV bid, adjusted, beginning day −1) and methotrexate (10 mg/m2 IV, day +1/+3/+6). RESULTS: 21 patients with a variety of hematologic malignancies (AML=4, MDS=5, NHL=5, CML/MPD=3, HD=2, MM=1, CLL=1) were enrolled. Mean age was 54 years (range 28–66). 7 patients had undergone prior autologous transplants. Median followup among surviving patients was 42 months (range 3–58 months). Peripheral blood chimerism at day +100 was >95% donor in 16/18 patients, 80% (with subsequent conversion to 95%) in one patient, and >95% recipient (with documented relapse) in one patient. Acute GVHD grade 1–2 was seen in 52% and grade 3–4 in 10% of patients. Chronic GVHD was observed in 9/20 evaluable patients (45%). Infectious complications included documented bacteremia (6 cases), candida albicans fungemia (1), aspergillus pneumonitis (3), nocardia pneumonitis (2), CMV viremia (6), CMV colitis (1). Veno-occlusive disease (self-limited, grade 1–2) was observed in 4/21 patients (19%). Relapse was observed in 5/21 patients (24%) at a median 249 days post-transplant (range 97–328 days). Event-free survival was 90% (19/21) at 100 days, 58% (11/19) at 1 year and 47% (8/17) at 3 years. Overall survival was 95% (20/21) at 100 days, 68% (13/19) at 1 year and 47% (8/17) at 3 years. Primary causes of death were relapse (4/9), infection (4/9), and idiopathic pneumonitis/multi-organ failure (1/9). Chronic GVHD was a significant contributing factor in 3/4 fatal infections. PTLD was observed in one patient, who subsequently died of CMV infection/sepsis syndrome. CONCLUSIONS. Allogeneic BM/SCT using a reduced intensity conditioning regimen is feasible among older patients, and those who are otherwise poor candidates for myeloablative BM/SCT regimens; however, GVHD, infection, and relapse remain formidable obstacles to achieving successful outcomes.

The Different Dynamics of Chimerism Evolution Determines the Success of Myeloablative, Reduced Intensity Conditioning and T-Cell Depleted Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5288-5288
Author(s):  
Ismael Buño ◽  
Pascual Balsalobre ◽  
Ainhoa Simón ◽  
Gustavo Iglesias ◽  
Cintia Manzano ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
T Lymphocytes ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Mixed Chimerism ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity

Abstract Background: The dynamics of chimerism evolution determines the success of allogeneic stem cell transplantation (SCT). Several factors such as the intensity of the conditioning regimen, the T-cell content of the graft or the GVHD prophylaxis, influence the degree of chimerism after SCT. Objective: To evaluate the dynamics of chimerism after different SCT settings (ablative, reduced intensity conditioning -RIC- and T-cell depleted -TCD-) and its influence in the success of the procedure. Patients and Methods: The study includes 68 SCT: 32 ablative (including 7 from HLA matched unrelated donors -UD-), 19 RIC and 17 TCD (including 8 from haploidentical donors and 2 from UD with 1 HLA disparity). Chimerism analysis was performed by FISH for the sex chromosomes or STR-PCR (sensitivity 1 Samples obtained on days +30, +100, +180, +365 and once a year thereafter, included bone marrow (BM) and peripheral blood (PB). Moreover, chimerism was analyzed in PB and leukocyte lineages (T lymphocytes CD3+, B lymphocytes CD19+ and myeloid cells CD15+ isolated (purity >95%) by immunomagnetic means, AutoMACS, Miltenyi Biotec), every 2 weeks, starting on day +15 (except in ablative), and until complete chimerism (CC) was achieved. Results of chimerism follow-up were censored once the diagnosis of relapse or rejection was established. Results: The incidence (% patients) of mixed chimerism (MC) on day +30 (ablative: BM 27%, PB 15%; RIC: BM 40%, PB 41%, CD3 40%; TCD: BM 31%, PB 33%, CD3 54%), as well as its dynamics (MC on day +100: ablative BM 8%, PB 4%; RIC BM 8%, PB 15%, CD3 22%; TCD BM 20%, PB 40%, CD3 37%) were different in the three SCT settings. All except 2 CD15 samples analyzed showed CC. Moreover, the percentage of recipient cells (%R) was significantly higher after RIC and TCD than after ablative SCT, as well as in T lymphocytes than in BM or PB (7/8 cases with simultaneous studies showed MC in T lymphocytes and CC in PB). All RIC SCT evolved to CC by day +180 while TCD SCT showed persistent MC (2 patients with stable MC after one year). The incidence of rejection was greater after RIC (2/19) and TCD (4/17) than after ablative SCT (2/32). All these patients showed MC, mainly in T lymphocytes, which allowed early diagnosis and successful treatment with immunosuppression withdrawal and donor leukocyte infusion. Patients with CC in PB/T lymphocytes on day +30 had a higher incidence of GVHD>I than those with MC. In the present series, however, a relationship between chimerism and relapse, disease free survival or overall survival, was not observed. Conclusions: SCT with greater incidence of MC (RIC and TCD) favor immune tolerance between donor and recipient which reduces the risk/severity of GVHD at the expense of a higher incidence of graft rejection.

Reduced Intensity Conditioning Regimens Do Not Offer a Survival Advantage to Myeloma Patients Receiving Allogeneic Stem Cell Hematopoietic Transplantation: A Societe Française De Greffe De Moelle Et De Therapie Cellulaire (SFGM-TC) Registry Study,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4113-4113
Author(s):  
Yvan Beaussant ◽  
Etienne Daguindau ◽  
Aurore Vivot ◽  
Mohamad Mothy ◽  
Herve Avet-Loiseau ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
New Drugs ◽  
Rank Test ◽  
Reduced Intensity Conditioning ◽  
Conditioning Regimens ◽  
Reduced Intensity

Abstract Abstract 4113 Purpose: Despite the raise of major new drugs in the management of multiple myeloma (MM), it is still an incurable disease and allogeneic stem cell transplantation (alloSCT) is currently the sole potential curative therapy mediated by a graft-versus-myeloma (GVM) effect. For over ten years, reduced intensity conditioning regimens (RIC) in alloSCT has been developed to maintain the GVM effect and to decrease the high transplanted related mortality (TRM) associated with myeloablative conditioning (MAC) in myeloma patients. Yet, as numerous studies have assessed RIC alloSCT versus autologous SCT, only few data provides a comparison between RIC and MAC for MM in large series. Our study aims to compare RIC and MAC alloSCT for MM on a large retrospective French cohort. Methods: We report a retrospective multicenter study based on the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) registry, evaluating the outcome of patients undergoing alloSCT for MM. Between 1995 and 2009, 811 patients allografted for MM were registered. Data concerning disease characteristics and the allograft procedure were screened using the French Promise® database; computerized discrepancy errors and data verification of every single file ensure data quality, important missing data were directly retrieved in each centre. We assign the type of conditioning regimen for each patient according to the registry's data reported by the local physician and check this information according to the following rules. We consider as myeloablative (MAC) all regimens containing > 8 mg/kg oral busulfan, > 600 cGY TBI, ≥ 200 mg/kg cyclophosphamide or combinations as BEAM like regimens. All other chemotherapy combinations with or without TBI are defined as RIC regimens generally including fludarabine. Patients were excluded when major data or conditioning information were not available; 566 patients (70% of the entire cohort) were finally eligible for analysis, 478 RIC and 88 MAC. Chi-squared test and T-test were used for comparisons. Survival analyses (Overall survival, OS; progression-free survival, PFS) are made using the Kaplan-Meier curve and log rank test. Multivariate analysis is made using the Cox proportional hazards model. Results: The RIC and MAC populations were statistically different regarding age (respectively 53 versus 46 years, p<.0001), number of prior transplant (> 1 prior transplant in 94% RIC versus 77% MAC, p<.0001), time to transplantation (<12 months after diagnosis in 22% RIC versus 38% MAC, p=.001) and stem cell source (peripheral blood 84% RIC versus 52% MAC, p<.0001, and bone marrow 10% RIC versus 45% MAC, p<.0001). The 2-year OS is 69.5% after RIC and 79.9% after MAC (p<.0001); 5-year OS is 49.7% after RIC and 60.2% after MAC (p<.0001, fig.1). The 2 year PFS is 49.3% and 70.1% and 5-year PFS is 29.6% and 40.8% after RIC and MAC respectively (p<.0001, fig.2). Factors associated with better OS and PFS in multivariate analysis are the following in the whole cohort: < 12 months between diagnosis and alloSCT (p=.0078 and p=.0037, respectively); disease status at transplantation (at least partial response, p=.0409 and p=.0026); no or limited acute graft-versus-host disease (GvHD) (p<.0001 and p=.0094) and presence of chronic GvHD (p<.0001 and p<.0001). On multivariate analysis, the intensity of conditioning regimen (RIC vs MAC) do not appear statistically significant for OS (p = 0.64) and PFS (p = 0.17). For patients transplanted between 2006 and 2009, neither high risk-cytogenetic nor bortezomib use before transplantation seems to affect the outcome in multivariate analysis. Conclusions: In the French practice, MAC regimens have had more limited indications due to their higher toxicity. This study suggests that the outcome after MAC-alloSCT is comparable to that after RIC-alloSCT with a trend to a better OS in the late follow-up (after 5 years) after MAC. The aspect of flattening in the survival curves suggests that the anti-tumoral action of the conditioning regimen remains essential on the anti-myeloma effect after alloSCT and that should be considered in the transplantation procedure. Disclosures: No relevant conflicts of interest to declare.

Comparison Of Unrelated Cord Blood (CB) and Peripheral Blood Stem Cell (PB) Transplantation In Adults With Myelodysplastic Syndrome (MDS) After Reduced Intensity Conditioning Regimen (RIC): A Collaborative Study From Eurocord and Chronic Malignancies Working Party (CMWP-EBMT)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3334-3334
Author(s):  
Marie Robin ◽  
Annalisa Ruggeri ◽  
Myriam Labopin ◽  
Dietger Niederwieser ◽  
Reza Tabrizzi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Myelodysplastic Syndrome ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Unrelated Cord Blood ◽  
Reduced Intensity

Abstract Background Outcome of patients with intermediate or high risk IPSS myelodysplastic syndrome (MDS) is poor in the absence of hematopoietic stem cell transplantation (HSCT). Choice of the best stem cell source is debated in this poor risk population. Unrelated cord blood transplantation (UCBT) has been used for patients lacking an HLA identical donor. This is the first study comparing well matched unrelated adult peripheral blood (PB) stem cell transplant to mismatched UCBT for patients with MDS. Method Patients with MDS transplanted from 2005 to 2011 with either unrelated CB or PB receiving a reduced intensity conditioning (RIC) were included. All PB donors were Human Leucocyte Antigens (HLA)-allele matched (10/10) or one allele mismatched (9/10) (-A, -B, -C, DRB1, -DQB1). Overall survival (OS) and disease-free survival (DFS) were estimated by Kaplan-Meier. Relapse incidence (RI), non-relapse mortality (NRM), engraftment, acute and chronic graft-versus-host disease (GVHD) were calculated using cumulative incidence (CInc) methods. Risk factors for outcomes were analyzed by Cox and Fine & Gray models. Results 502 patients transplanted with PB or 129 with CB (80 with double units) were compared. Among the PB recipients, 363 (72%) were 10/10 matched and 123 (25%) 9/10 matched. Most CB (98%) recipients had at least one HLA mismatch on 6 antigens tested (-A, -B antigen level and DRB1 allelic level), 32% had one mismatch and 66% had 2 mismatches. Median follow-up was 12 months for PB and 24 months for CB. MDS was transformed into AML in 416 patients. MDS WHO classification was: RA in 37, RCMD in 31, RAEB1 in 50 and RAEB2 in 87 and unclassified in 10 patients. Considering only patients with MDS, cytogenetic according to IPSS was: good in 96, intermediate in 57 and poor in 65 patients. PB and CB groups were different for age, gender, incidence of secondary AML (CB: 71% vs PB: 64%) and conditioning regimen. CInc of engraftment was lower in CB patients, 78 vs 96% (p<0.0001). Grade II to IV acute GVHD was 29% and 31% for PB and CB. Chronic GVHD was more frequent after PB (42% vs 23%, p=0.001). The unadjusted 2-year OS and DFS were better in patients transplanted with PB (46% vs 30% and 43% vs 28%, p=0.0001). There was no statistical difference for OS and DFS between single and double UCBT. RI was not significantly different (25 vs 30%, p=0.09) whereas NRM was higher in patients transplanted with CB (42 vs 33%, p=0.02). In multivariate analysis, OS (Hazard ratio (HR): 0.59, 95% confidence interval (CI): 0.44-0.80) and DFS (HR: 0.57, 1.89, 0.79) were higher in patients transplanted with PB compared to CB. Furthermore, after adjustment, CB was also a risk factor for higher NRM ((PB, HR: 0.55, 95%CI: 0.37-0.80) and RI ((PB, HR: 0.62, 95%CI: 0.39-0.97). The analyses were performed using 3 groups of patients according to donor HLA type: PB 10/10, PB 9/10 and CB. The unadjusted 2-year OS and DFS were better with PB 10/10 than with PB 9/10 or CB: 49%, 37% and 30% (p=0.0001) and 45%, 36%, 28% (p<0.0001), respectively. NRM was not significantly different between CB and PB 9/10: 42% vs 36%. RI was similar after CB and PB 9/10: 28% vs 30%. Chronic GVHD was significantly lower after CB (PB 9/10: 37% vs CB 23%, p=0.004). The multivariate analysis showed an advantage of OS for PB 10/10 compared to PB 9/10 (HR: 1.45, 95%CI: 1.06-1.97, p=0.02) whereas there was no significant difference between PB 9/10 and CB (HR: 1.24, 95%CI: 0.84-1.83, p=0.29). Likewise, DFS was better after PB 10/10 (HR: 0.57, 95%CI: 0.43-0.77, p=0.05) and it was similar after PB 9/10 or CB (HR: 1.34, 95%CI: 0.92-1.97, p=0.13). In the 9/10 PB no differences in the results were observed according to the specific mismatched locus (A, B, DRB1, vs C, DQB1) Conclusion Despite the limitation of a retrospective registry based study and the short term follow up, our study shows that transplants with PB from matched unrelated donor gives the best outcomes. In the absence of a 10/10 unrelated matched PB donor, a 9/10 PB donor or mismatched CB give similar results. Therefore, for MDS patients without a HLA 10/10 unrelated donor a 9/10 regardless of the specificity of the locus where the mismatch occurs mismatched HLA locus or a HLA mismatched CB are both alternative options for transplantation. Disclosures: Gluckman: Cord use: Honoraria; gamida: Honoraria.

Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors

Blood ◽  
2003 ◽  
Vol 102 (10) ◽  
pp. 3829-3836 ◽  
Author(s):  
Naoto T. Ueno ◽  
Yee Chung Cheng ◽  
Gabriela Rondón ◽  
Nizar M. Tannir ◽  
James L. Gajewski ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Solid Tumors ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Donor Chimerism ◽  
Reduced Intensity

AbstractWe evaluated the feasibility and efficacy of a reduced-intensity conditioning (RIC) regimen of fludarabine and melphalan to achieve rapid complete donor chimerism after allogeneic stem cell transplantation (SCT) in patients with metastatic solid tumors. Between January 1999 and January 2003, 8 patients with metastatic breast cancer (BC) and 15 with metastatic renal cell carcinoma (RCC) underwent allogeneic SCT after an RIC regimen of 5 days of fludarabine and 2 days of melphalan. Filgrastim-mobilized stem cells from HLA-identical related or unrelated donors were infused. Prophylaxis for graft-versus-host disease (GVHD) consisted of tacrolimus and methotrexate. All 22 evaluable patients had 100% donor chimerism at day 30 and at all measurement times thereafter. One patient died 19 days after SCT. Nine patients (39%) had grades II to IV acute GVHD and 10 patients (43%) had chronic GVHD. Five patients (22%) died of nonrelapse treatment-related complications. Treatment-related disease response was seen in 10 patients (45%), with 3 complete responses, 2 partial responses, and 5 minor responses. Fludarabine-melphalan is a feasible and effective RIC regimen for allogeneic SCT in metastatic BC and RCC. It induces rapid complete donor chimerism without the need for donor lymphocyte infusion. Tumor regression associated with GVHD is consistent with graft-versus-tumor effect. (Blood. 2003;102:3829-3836)

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