Comparison of Cyclosporine A and Mycophenolate Mofetil vs Cyclosporine A and Methotrexate in Reduced Intensity Conditioning HLA Sibling Allogeneic Stem Cell Transplantation. A Case-Match Single-Center Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4994-4994
Author(s):  
Jose L. Piñana ◽  
David Valcárcel ◽  
Rodrigo Martino ◽  
Rocio Parody ◽  
Anna Sureda ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mycophenolate Mofetil ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cyclosporine A ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Reduced Intensity Conditioning ◽  
Gvhd Prophylaxis ◽  
Reduced Intensity

Abstract BACKGROUND: Graft-versus-host disease (GVHD) is the major obstacle to successful allogeneic stem cell transplantation (SCT) transplantation. Cyclosporine (Csa) in combination with methotrexate (MTX) is the most commonly used prophylactic regimen. The combination of CsA and Mycophenolate Mofetil (MMF) has recently been introduced. In this case-match study we retrospectively analyzed the introduction of MMF as GVHD prophylaxis in comparison with a short course of MTX in the setting of reduced intensity conditioning allogeneic SCT (Alo-RIC). PATIENTS AND METHODS: We analyzed 59 Alo-RIC recipients who received an Alo-HSCT from an HLA-identical sibling between April 2000 and June 2006. The median follow-up for the whole group was 473 days (8 to 2139 days). The study group included 40 males and 19 females. Median age was 59 years (range 43 to 72). Diagnoses were acute leukemia/myelodisplastic syndrome) (n=19/22), mutiple myeloma (n= 6), chronic myeloid leukemia (n=5) and non- Hodgkin lymphoma (NHL) (n= 4). GVHD prophylaxis consisted of Csa/MTX (MTX group) in 37 patients and Csa/MMF (MMF group) in 22 patients. The conditioning regimen was based on fludarabine in combination with busulfan (42 recipients) or melfalan (17 cases). RESULTS: The occurrence of mucositis grade 2–4 was higher in the MTX group than in the MMF group (62% vs 28% p= 0.015). No significant differences were found between MMF vs MTX groups in time to neutrophil recovery (16 +/−3 days vs 15 +/− 2days) (p= 0.5). Median time to the achievement of complete T-cell donor chimerism in the MTX and MMF groups was 79 days (range 19–740) and 76 days (range 24–223) respectively (P=0.4). The 1- year non-relapse mortality was similar in MTX and MMF groups 14% (95% C.L. 6–31%) vs 28% (95% C.L. 13–60%) respectively; P=0.2. Cumulate incidence of acute GVHD for MTX and MMF groups was 49% (95% C.L. 35–68%) and 68% (95% C.L. 51–91%) respectively (P= 0.6). Patients in the MTX group showed a trend to a higher incidence of chronic GVHD than the Csa/MMF group, 55% (95% C.L. 40–74%) vs 42% (95% C.L. 23–75%) (P=0.2). No differences were found between MTX vs MMF groups in 1-year overall survival [78%(64–92%) vs 53%(38–76%); P=0.1] nor in 1-year relapse incidence [37% (95%CI 21–64%) vs 19% (95%CI 10–37%) P=0.1) We conclude that the Csa/MMF combination appears to be equivalent to the standard Csa/MTX aGVHD prophylaxis in Alo-RIC. MMF showed significantly less mucositis.

Pilot Study of Reduced-Intensity Conditioning Followed by Allogeneic Stem Cell Transplantation in Patients with Myelofibrosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1512-1512
Author(s):  
Nicolaus Kroeger ◽  
Tatjana Zabelina ◽  
Heike Schieder ◽  
Jens Panse ◽  
Francis Ayuk ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pilot Study ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity

Abstract We evaluated in a prospective pilot- study the effect of reduced intensity conditioning with busulfan (10 mg/kg), fludarabine (150 mg/m²) and anti-thymocyte globulin followed by allogeneic stem cell transplantation from related and unrelated donors in 14 patients with myelofibrosis. Study objectives were engraftment, chimerism, treatment- related mortality (TRM) and response. The median age of the patients was 51 (range, 32 – 63) years. According the Lille score there were low risk (n=4), intermediare risk (n= 7) and high risk (n=3) The median time until leukocyte (> 1.0 x 109/l) and platelet (> 20 x 109/l) engraftment was 16 (range, 11 – 26) days and 26 (range, 9 – 139) days, respectively. No graft failure occurred. Complete donor chimerism on day 100 was seen in 13 patients (93%). Acute graft-versus host disease (GvHD) grade II-IV occurred in 50% and grade III/IV 29 % of the patients. The incidence of chronic GvHD was 54 %. Two patients died due to treatment complications, resulting in a TRM at one year of 15% (95% CI: 0–35%). Hematological response after allogeneic transplantation was seen in all patients and complete histopathological remission was observed in 90%of patients. After a median follow-up of 13 (range, 3 – 48) months, the 3-years estimated overall and disease-free survival is 85 % (95 % CI: 65–100 %).

Allogeneic Stem Cell Transplantation (allo-SCT) from a HLA Identical Sibling for CR1 AML Patients Aged above 55 Years Old after a Reduced Intensity Conditioning: A Survey from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1140-1140
Author(s):  
Didier Blaise ◽  
Zina Chir ◽  
Michel Attal ◽  
Jean-Henri Bourhis ◽  
Jean-Jacques Sotto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
High Survival ◽  
Reduced Intensity Conditioning ◽  
Preparative Regimen ◽  
The Impact ◽  
Reduced Intensity

Abstract Background: AML incidence increases with age. Allogeneic stem cell transplantation (Allo-SCT) offers the best leukemic control but is associated with high non-relapse mortality (NRM). Recent advances using non-myeloablative strategies have established the feasibility of allo-SCT in elderly patients. However in the context of AML, an important reduction of the intensity of the preparative regimen may be also associated with a loss of leukemic control, offsetting the impact of toxicity reduction in elderly. Methods: We retrospectively analyzed AML patients in first complete remission (CR1) reported to the SFGM-TC, aged above 55 and transplanted from a HLA identical sibling donor prior to 01/01/05. Results: 62 patients prepared with a non-myeloablative conditioning (NMAC) (fludarabine (75mg/m2) + TBI (2Gy)) (N=14) or a reduced intensity conditioning (RIC) (busulfan (4 to 8 mg/m2) + fludarabine (150 to 180 mg/m2) + thymoglobulin (2.5 to 12.5 mg/m2)) (N=48). GVHD prophylaxis used CSA+MMF for NMAC, CSA +/− MMF for RIC. With few exceptions, all patients in a given centre were treated identically. Major characteristics were: age 58 (55–67), M/F= 27/35. Time between diagnosis and allo-SCT: 171 days (101–467). BMT/PBSCT: 7/55. Pts have been considered for allo-SCT because of poor prognosis factors: no favorable cytogenetics (100%), secondary AML (15%), 2 chemotherapy course to achieve CR1 (24%) or M0, M6 or M7 FAB (20%). All pts engrafted. Acute GVHD occurred in 16 pts (grade 1: 6; grade 2: 6; grade 3–4: 4) and chronic GVHD in 18 pts (limited: 8; extensive: 10) with no difference in the 2 groups. The cumulative incidences of grade 2–4 aGVHD and cGVHD were 16% (95%CI: 7–25) and 29% (95%CI: 18–40) respectively. 15 pts relapsed and 8 died from NRM. Relapse and NRM cumulative incidences were 24% (95%CI: 13–35) and 13% (95%CI: 5–21) respectively. 49 pts were evaluable for cGVHD: of the 18 expressing cGVHD none have relapsed as compared to 12 of the 31 who did not present cGVHD (39%, 95%CI: 22–56) (p=.007). The 2 year KM survival and DFS probabilities are 63% (47–76) and 56% (42–69). In a landmark analysis investigating patients alive on day 100, 2 year DFS are 94% and 38% respectively with or without cGVHD (p=0.001) and 2 year KM OS are respectively 94% and 45% (p=0.01). Conclusions: We conclude that such a strategy in elderly can afford a high relapse control with low NRM conducting to high survival probability at 2 years. Results are achieved through the allogeneic effect as expressed by cGVHD inviting to a careful immunomodulation in the early post transplant period to further improve results.

Cyclosporine a and Mycophenolate Mofetil Vs Cyclosporine a and Methotrexate as Gvhd Prophylaxis in Reduced Intensity Conditioning Hematopoietic Stem Cell Transplantation from HLA-Identical Sibling Donor.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2229-2229
Author(s):  
Jose Luis Piñana ◽  
David Valcarcel ◽  
Rodrigo Martino ◽  
Francesc Fernandez ◽  
Pere Barba ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mycophenolate Mofetil ◽  
Cyclosporine A ◽  
Chronic Gvhd ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Sibling Donor ◽  
Gvhd Prophylaxis ◽  
Reduced Intensity

Abstract J.L.Piñana is supported by grants from the Instituto de Salud Carlos III (expedient CM06/00139, Ministerio de Sanidad) Background: Cyclosporine A (Csa) with methotrexate (MTX) is the most common prophylactic regimen against acute graft versus host disease (aGVHD). Although some studies show that Mycophenolate Mofetil (MMF) in combination with Csa for patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is associated with early hematologic recovery, less toxicity as mucositis and no diferencies in terms of aGVHD. Limited data is available comparing these two combinations in reduced intensity conditioning Allo-HSCT (Allo-RIC). In this case-control study from two Spanish BMT centers, we retrospectively analyzed the introduction of MMF as GVHD prophylaxis in comparison with a short course of MTX in a large series of patients who underwent HLA identical sibling donor Allo-RIC. Patients and methods: We include 145 consecutive Allo-RIC patients, who received peripheral blood (PB) as source of stem cells, between April 2000 and August 2007. The median follow-up for the whole group was 514 days (8 to 3170 days). The study group included 91 males and 54 females. Median age was 55 years (range 18 to 71 years). Diagnoses were acute leukemia/myelodisplastic syndrome/myeoloproliferative disorders) (n=37/15/13), multiple myeloma (n= 32), Hodgkin lymphoma (n= 6), chronic lymphocytic leukemia (n=15) and non-Hodgkin lymphoma (NHL) (n= 27). GVHD prophylaxis consisted of CsA/MMF in 52 and CsA/MTX in 93 patients. The conditioning regimen was based on fludarabine in combination with busulfan (59 recipients) or melphalan (86 cases). Results: The occurrence of mucositis grade 2–4 was higher in the CsA/MTX group than in the CsA/MMF group (57% vs 23% p= 0.001). No significant differences were found between CsA/MMF and CsA/MTX groups in time to neutrophil recovery (15 +/−3 days vs 15 +/− 2days) (p= 0.5). Cumulate incidence of acute GVHD were 50% (95% C.I., 38–65) for CsA/MMF group and 48% (95% C.I. 39–60%) for CsA/MTX group (p= 0.9). Although chronic GVHD was also similar [71% (95% C.I. 58–86%) in CsA/MMF group vs 68% (95% C.I. 57–80%) in Csa/MTX group (p= 0.7)], we observed that the development of chronic GVHD was delayed in the CsA/MMF group [174 days (range 100–365) vs 134 days (range 84–302) p= 0.008)]. Non relapse mortality (NRM) at 100 days was higher in MTX group (6% vs 18%, p=0.04). However, relapse and overall survival at median follow-up were still similar between groups (25% vs 18%, p= 0.4 and 52% vs 51%, p=0.7, respectively). Conclusion: We conclude that the combination Csa/MMF appears to be at least equivalent to the standard Csa/MTX GVHD prophylaxis in HLA identical sibling donor Allo-RIC. The toxicity profile of Csa/MMF was better, reflected by a significantly less incidence of mucositis.

scholarly journals Alemtuzumab As Pre-Conditioning Is Safe and Feasible in Patients with T-Cell Lymphoid Neoplasms Undergoing Allogeneic Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5863-5863
Author(s):  
Sara Lozano ◽  
Amaya Zabalza ◽  
Intza Aoiz ◽  
Mohamed Hamdi Djatri ◽  
Pedro Arregui ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
Chronic Gvhd ◽  
Infectious Complications ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity

Abstract Background: In vivo T-cell depletion with Alemtuzumab reduces the incidence of acute and chronic graft-versus-host disease (GvHD) and graft failure, yet it results in an increase of opportunistic infections and delayed immune recovery. In addition, Alemtuzumab has considerable anti-lymphoma activity in T-cell neoplasms. We report on a pilot study analysing the safety and feasibility of Alemtuzumab as pre-conditioning prior to reduced intensity conditioning allogeneic stem cell transplantation (RIC-alloSCT) in patients diagnosed with T-cell non-Hodgkin lymphoma. Methods: Six consecutive patients diagnosed with a T-cell lymphoid malignancy underwent RIC-alloSCT from a HLA-identical sibling (n=5) or a matched unrelated donor (n=1). Diagnosis were Angioimmunoblastic T-cell lymphoma (n=3), hepato-splenic gamma-delta T-cell lymphoma (n=1), T/NK cavum lymphoma (n=2) and Sèzary Syndrome (n=1). All received unmanipulated peripheral blood stem cells; At transplantation 2 patients were in CR, and 4 in PR. Median number of prior regimens was 2 (range 2-5). Conditioning regimen included Fludarabine (5 x 30mg/m2) and Melphalan (2 x 70mg/m2) in all cases. GvHD prophylaxis comprised Cyclosporine A and Methotrexate. The pre-conditioning protocol consisted on 6 escalating doses of intravenous Alemtuzumab starting on day -28 (3 mg on day -28, 10 mg on day -26 followed by four doses of 30 mg on days -24 to -17) given 3 times a week (MWF) on an out-patient basis. Results: Five patients received all six doses of Alemtuzumab as planned whereas one patient received only four doses for logistic reasons related to donor availability. Acetaminophen, Hydrocortisone and Dexchlorpheniramine were administered as pre-medication in all cases with no severe infusional reaction observed. There were no delays in proceeding to SCT conditioning and patients develop no infectious complications during the Alemtuzumab - alloSCT interval. All patients engrafted with a median time to neutrophil engraftment of 23 days (range 14-27). Acute skin GvHD (grade I and III) was observed in 2 patients (33.3%), both obtaining a CR with topical and systemic corticosteroids respectively. Two patients developed mild ocular chronic GvHD (one after subsequent infusions of donor lymphocytes - DLI) but none has suffered from extensive chronic GvHD. No opportunistic infection was observed apart from CMV reactivation that developed in 3 out of 4 seropositive patients (no CMV disease was observed). All patients experienced delayed immune reconstitution (CD4 >200/ul) at a median of 321 days (range 229-518). All 4 patients in PR prior to alloSCT achieved a complete remission. Only one patient (diagnosed with Sèzary Syndrome) experienced a relapsed and responded to DLI. With a median follow-up of 42 months, all patients remain alive and in CR. Conclusions: Our preliminary results suggest that administration of Alemtuzumab prior to reduced intensity conditioning is feasible and safe. In addition to providing T-cell depletion, Alemtuzumab may improve the response rate in T-cell lymphoid malignancies without increasing the risk of infectious complications. These results require further validation in larger phase II studies. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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.

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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