scholarly journals Use of a reduced-intensity conditioning regimen for allogeneic transplantation in patients with chronic myeloid leukemia

2003 ◽  
Vol 32 (2) ◽  
pp. 125-129 ◽  
Author(s):  
M Das ◽  
T K Saikia ◽  
S H Advani ◽  
P M Parikh ◽  
S Tawde
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity Conditioning Regimen ◽  
Reduced Intensity

Phase I/I Clinical Trial for the Evaluation of Bortezomib within the Reduced Intensity Conditioning Regimen (RIC) and Post-Allogeneic Transplantation As Gvhd Prophylaxis Among High-Risk Myeloma Patients. EudraCT: 2005–004858-27

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3025-3025
Author(s):  
Jose Antonio Perez-Simón ◽  
Teresa Caballero-Velazquez ◽  
Cristina Encinas ◽  
Cristina Castilla-Llorente ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
Reduced Intensity Conditioning ◽  
Advisory Committees ◽  
Gvhd Prophylaxis ◽  
Reduced Intensity Conditioning Regimen ◽  
Reduced Intensity

Abstract Abstract 3025 Introduction: Although allogeneic stem cell transplantation (allo-SCT) is the only curative treatment for MM, it is associated to a high morbility and mortality. Moreover, relapses are common after allo-RIC. Accordingly, new strategies are required to reduce both the risk of relapse and the toxicity of the procedure. As we have previously demonstrated, Bz induces a selective depletion of alloreactive T-cells and has immunomodulatory properties which might be of potential benefit for GVHD control. The primary end point of this study was to evaluate the efficacy of allo-RIC in terms of response when Bz was added as part of a reduced intensity conditioning prior to allo-SCT. Secondary end points included incidence of GVHD and analysis of the toxicity of the procedure when Bz is also administered post-infussion as part of the GVHD prophylaxis. Method: Prior to allo-RIC, patients received two cycles of Bz plus dexamethasone. Conditioning consisted of fludarabine (30 mg/m2 intravenously on days -9 to -5) and melphalan (70 mg/m2 intravenously on days -4, -3) plus Bz 1, 3mg/m2 on day - 11 and -2. GVHD prophylaxis included cyclosporine (CsA) and methotrexate for the first 9 patients and CsA plus MTX and Bz on days +3 and +7 for the remaining 7 patients. From day +50 post allo-RIC 7 cycles of Bz (+1, +8, +15) were administered, the first two cycles every 28 days and the rest every 56. Results: 16 patients from the Twenty-one initially enrolled, were evaluable. All 16 patients had received at least 2 lines of therapy including autologous-SCT. Disease status was CR or nCR in 4 patients, 9 had PR and the remaining 3 patients had relapsed / progressive disease. 15 patients maintained or improved status at transplant including all × patients with active disease at transplant. Eight patients (50%) relapsed, four with extramedullary involvement. No patient developed grade 4 aGVHD.Grades 2–3 aGVHD occurred in 6 patients (37%). Interestingly, two out of the nine (29%) patients who received Bz on days +3 and 7 developed grades 2–3 acute GVHD as compared to four of the nine (44%) who did not receive it. In terms of toxicity, one patient did not achieve platelet engraftment and 2 patients developed peripheral neuropathy requiring treatment withdrawal. 8 patients died, four of them due to relapse (MRT: 25%). With a median follow-up of 457 days overall survival was 46%. Conclusions: The current trial is the first evaluating the efficacy and safety of Bz as part of a reduced intensity conditioning regimen among patients with high risk MM undergoing allogeneic transplantation. Regarding the efficacy of the procedure all but one patient improved disease status post-alloRIC although relapse rate was still high in this heavily pretreated population. In addition, Bz post-alloSCT is well tolerated and may decrease the incidence of GVHD. Disclosures: Perez-Simón: Janssen-Cilag: Patents & Royalties. Off Label Use: This study evaluates the efficacy of Bortezomib as part of a reduced intensity conditioning regimen among patients with high risk MM undergoing allogeneic transplantation. Rosiñol:Celgene: Honoraria; Janssen: Honoraria. San Miguel:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Clofarabine versus fludarabine‐based reduced‐intensity conditioning regimen prior to allogeneic transplantation in adults with AML/MDS

2016 ◽  
Vol 5 (11) ◽  
pp. 3068-3076 ◽  
Author(s):  
Patrice Chevallier ◽  
Myriam Labopin ◽  
Regis Peffault La Tour ◽  
Bruno Lioure ◽  
Claude‐Eric Bulabois ◽  
...  
Keyword(s):  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity Conditioning Regimen ◽  
Reduced Intensity

Comparison of Reduced-Intensity Conditioning Regimen and Conventional Conditioning Regimen for Allografting in Chronic Myeloid Leukemia in the First Chronic Phase.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4658-4658
Author(s):  
Michael Doubek ◽  
Marta Krejci ◽  
Yvona Brychtova ◽  
Jiri Mayer
Keyword(s):  
Total Dose ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Chronic Phase ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity Conditioning Regimen ◽  
Blood Stem Cells ◽  
Reduced Intensity

Abstract The role of conventional allogeneic blood stem cells transplantation (SCT) in the treatment of chronic myeloid leukemia (CML) in the first chronic phase (CP) is not exactly defined yet. The role of allogeneic transplantation after the reduced-intensity conditioning regimen is even more unclear. Our work aims to compare the effect of reduced-intensity conditioning regimen and conventional conditioning regimen in the treatment of CML in the first CP. We performed a retrospective analysis of the patients with CML, who underwent the allogeneic SCT in our department from 1997 after a conventional regimen BuCy (busulfan in a total dose of 14–16mg/kg and cyclophosphamide in a total dose of 120 mg/kg) and after reduced-intensity regimen comprising of fludarabine (Flu, in a dose 30 mg/m2/d, 6 days) oral busulfan (Bu) in a total dose 8 mg/kg, and ATG at a dose of 10 mg/kg/d (4 days). For the analysis we chose as comparable groups of patients as possible. We analysed only patients with transplanted peripheral blood stem cells from their HLA identical sibling. Into the analysis we included 17 patients transplanted after the regimen BuCy and 13 patients transplanted after the regimen Flu+Bu+ATG. The patients transplanted after the regimen Flu+Bu+ATG were significantly older in comparison to the patient transplanted after the regimen BuCy (median of 51 years compared to 33 years). The median period from the date of diagnosis till the date of transplantation was 6 months in regimen Flu+Bu+ATG and 5 months in regimen BuCy. A profylaxis of the graft-versus-host disease (GVHD) comprised of cyclosporine A in regimen Flu+Bu+ATG and of cyclosporine A plus methotrexate in regimen BuCy. After the regimen BuCy we noticed higher mortality till the day +100 (11.8% versus 0; p<0.01), higher incidence of acute GVHD (76.5% versus 38.5%; p=0.05), higher incidence of hepatic veno-occlusive disease (VOD) (11.8% versus 0; p<0.01) and higher non-hematologic toxicity (100% versus 76.5%; p<0.01). The two compared regimens do not significantly differ in the incidence of chronic GVHD, cytomegalovirus reactivation and febrile neutropenia. We did not find any difference in the induction of complete chimerism after the transplantation. After the regimen BuCy it was observed that the achievement of complete molecular remission (CMR) of the disease was faster. Six months after transplantation, the ratio of patients in CMR was 64.7% (BuCy) versus 46.1% (Flu+Bu+ATG). At the present time 70.6% of patients transplanted after the regimen BuCy and 76.9% after the regimen Flu+Bu+ATG are in CMR. Stable sustained CMR has been observed in 70.6% of patients treated by regimen BuCy and in 53.8% of patients treated by Flu+Bu+ATB (non-significant). Four patients died consequent to the transplantation after the regimen BuCy (on VOD, bleeding, ARDS and extensive chronic GVHD with sepsis) and one patient after the regimen Flu+Bu+ATG (on relaps of the leukemia and GVHD after the donor lymphocyte infusion). A long-term survival is 76.5% of patients transplanted after BuCy and 92.3% of patients transplanted after Flu+Bu+ATG. After the regimen Flu+Bu+ATG we have found 4 relapses (one haematological and 3 molecular), after the regimen BuCy we have found 3 relapses, all of them were molecular. Our comparison shows, that the regimen BuCy is more toxic, on the other hand it leads to sustained CMR more often. When analysing the overall survival, both regimens are equal, despite the fact that the regimen Flu+Bu+ATG was used in older patients.

Gemtuzumab Ozogamicin (Mylotarg®) as Part of Reduced-Intensity Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients with Relapsed Acute Myeloid Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1245-1245
Author(s):  
Martin Bornhaeuser ◽  
Thomas Illmer ◽  
Uwe Platzbecker ◽  
Johannes Schetelig ◽  
Markus Schaich ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Liver Toxicity ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Gemtuzumab Ozogamicin ◽  
Reduced Intensity Conditioning ◽  
Conditioning Therapy ◽  
Reduced Intensity ◽  
Acute Myeloid

Abstract Gemtuzumab ozogamicin (GO) has been successfully used in older patients with relapsed CD33+ acute myeloid leukemia. Retrospective analyses suggest that the use of GO within a few months before or after hematopoietic stem cell transplantation (HCT) is associated with a increased risk for sinusoidal obstruction syndrome (SOS) or veno-occlusive liver disease (VOD). Ongoing studies investigate the use of GO in the induction and post-remission therapy of AML patients. We hypothesized that GO might be safe and effective as part of a reduced intensity conditioning regimen containing fludarabine and total-body irradiation (TBI) Fifteen patients relapsing after conventional induction chemotherapy (n=9) or after previous transplantation (autologous n=3; allogeneic n=3) were included so far. The last twelve patients were treated within an ongoing phase II trial. The preparative regimen contained 6 mg/m2 and 3 mg/m2 GO on day −21 and day −14 before allogeneic transplantation. Patients who responded to GO treatment and were below the age of 60 (n=8) received fludarabine 120 mg/m2 and 800 cGy TBI (n=6) during GO-induced aplasia followed by allogeneic HCT. Patients older than 60 years or those with relapsing AML <12 months after the first transplant received 200 cGy TBI (n=7). Tacrolimus and mycophenolate mofetil was administered as GvHD prophylaxis in all patients. Two patients with refractory disease did not undergo transplantation. Six patients (40%) had a complete or partial response and directly proceeded to allogeneic transplantation. In seven cases without response to GO, an additional salvage regimen was directly followed by conditioning therapy and transplantation. Patients received G-CSF mobilized peripheral blood progenitor cells from matched-sibling (n=4) or unrelated donors (n=9) with a maximum of 1 allele mismatch (9/10). Primary engraftment was observed in all patients. Only one patient experienced grade 4 hyperbilirubinemia associated with sepsis and death on day +11. Grade I liver toxicity was observed in four patients. With a median follow-up of 10 months (range 1−48), no case of SOS, VOD or delayed liver toxicity was documented. Grade II–IV acute GvHD occurred in 7 patients (54%). Out of seven patients alive, six are still in complete remission. Reasons for death in the other patients were leukemia relapse (n=6) and acute GvHD (n=2). Patients who responded to GO had a significantly higher probability of disease-free survival (67%) at one year than patients whose blast counts could not be reduced by GO treatment (0%, p=0.007). These data suggest, that GO can be combined with a TBI-containing, fludarabine-based conditioning regimen before allogeneic HCT in patients with relapsed AML. No increased incidence of VOD has to be expected even in recipients who had undergone previous conditioning therapy and transplantation. Nevertheless, additional chemotherapy during aplasia before allogeneic transplantation is required in 60–70% of patients who do not respond to GO. For responding patients the combined regimen is associated with minimal toxicity and a considerable chance for long-term cure.

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