Reduced-intensity allogeneic hematopoietic stem cell transplantation for acute leukemias: ‘what is the best recipe?’

Kassim, Adetola A.; Chinratanalab, Wichai; Ferrara, James L.M.; Mineishi, Shin

doi:10.1038/sj.bmt.1705075

Cited by 25 publications

(19 citation statements)

References 96 publications

(97 reference statements)

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“…Regimens have been classified according to the degree of myelosuppression and immunosuppression that they induce. 6 These differences have been shown to influence the kinetics of engraftment and response. [7][8][9][10][11] The combination of fludarabine phosphate with melphalan (Flu/Mel) in RIC regimens is a moderately intensive regimen.…”

Section: Introductionmentioning

confidence: 99%

Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen suitable for allogeneic transplantation that maintains the graft versus malignancy effect

Dasgupta

Rule

Johnson

et al. 2006

Bone Marrow Transplant

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Reduced intensity conditioning (RIC) for allogeneic stem cell transplantation allows stable donor cell engraftment with the maintenance of a graft versus malignancy effect. Many different regimens exist employing various combinations of chemotherapy, radiotherapy and T-cell depletion. We examined the role of non-T-cell depleted RIC regimens in 56 patients with haematological malignancies. Patients received fludarabine phosphate for 5 days (30 mg/m 2 in 35 patients, 25 mg/m 2 in 21 patients) and melphalan for 1 day (140 mg/m 2 in 36 patients, 100 mg/m 2 in 20 patients). Immunosuppression was with CyA alone in 33 patients and CyA/MTX in 23 patients. Twenty-four of the 26 patients with chimerism data showed 495% donor chimerism at 3 months post transplant. aGVHD occurred in 18% of patients receiving CyA/MTX compared to 53% of patients receiving CyA. The 100-day mortality rate was 0.16 (95%CI 0.08-0.28) and 1-year nonrelapse mortality was 0.24 (95%CI 0.13-0.38). Thirty-three patients remained alive and in CR at a median of 19 months post transplant (range 3-38 months). We have shown that patients transplanted with fludarabine phosphate, melphalan 100 mg/m 2 and with CyA/MTX as post transplant immunosuppression can achieve good disease control with an acceptable level of toxicity. Further studies are required to confirm these findings.

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Section: Introductionmentioning

confidence: 99%

Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen suitable for allogeneic transplantation that maintains the graft versus malignancy effect

Dasgupta

Rule

Johnson

et al. 2006

Bone Marrow Transplant

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“…Existing therapies for leukemia rely on chemotherapy composed of steroids, anthracyclines and nucleoside analogs, and/or stem cell transplantations. [1][2][3] Despite a relatively high cure rate (upwards of 85%), long-term sequelae are often seen in patients and include cardiac complications and an increased risk of second malignancies. 4,5 Therefore, a major challenge in leukemia research is to develop new therapies to decrease toxicity, maintain remission, and prolong survival of patients.…”

Section: Introductionmentioning

confidence: 99%

Caspase-8 dependent histone acetylation by a novel proteasome inhibitor, NPI-0052: a mechanism for synergy in leukemia cells

Miller¹,

Rudra²,

Keating

et al. 2009

Blood

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“…3 Since the late 1990s, several other non-myeloablative regimens have been developed, using PBSC as source of stem cells. 5 This choice is explained by the high level of CD34 + cells and T lymphocytes in PBSC grafts, which allows a better engraftment than BM grafts. [8][9][10][11][12] However, PBSC has also been shown to increase the risk of chronic GVHD (cGVHD) compared with BM.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5] Traditionally, the goal of the preparative regimen has been eradication of the malignancy as well as providing sufficient immunosuppression and creating marrow space to prevent graft rejection. This belief has been questioned to reduce the toxicity of the conditioning and generate more graft-versus-malignancies effects.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow graft as a source of allogeneic hematopoietic stem cells in patients undergoing a reduced intensity conditioning regimen

Gómez¹,

Duléry²,

Langlois

et al. 2014

Bone Marrow Transplant

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In an attempt to reduce the incidence of chronic GVHD (cGVHD) after reduced-intensity conditioning (RIC), we used BM instead of PBSC and added melphalan 100 mg/m 2 to the classical association of fludarabine, 30 mg/m 2 /day for 3 days and TBI, 200 cGy (FLUIM regimen). Between 2000 and 2012, 51 patients received BM with the FLUIM regimen (group A), and 124 received BM (n = 22) or PBSC (n = 102) with another RIC regimen (group B). Donors were siblings (n = 123) or HLA-matched 10/10 unrelated (n = 52). Full donor-type chimerism at day 100 was more often recorded in group A (86%) than in group B (62%); P o0.001. There was no difference between the two groups in terms of OS and EFS, acute GVHD, relapse and non-relapse mortality incidence. cGVHD occurred more often in group B (41%) than in group A (23%); P = 0.021. In multivariate analysis, the two risk factors associated with the development of cGVHD were conditioning in group B (hazard ratio (HR) = 2.871, 95% confidence interval (CI) (1.372-6.006); P = 0.005) and CD34 + count (HR = 1.009, 95% CI (1.006-1.011); P o 0.001). In conclusion, the FLUIM regimen followed by BM leads to more frequent full-donor chimerism and a reduced incidence of cGVHD without compromising relapse and survival.

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Reduced-intensity allogeneic hematopoietic stem cell transplantation for acute leukemias: ‘what is the best recipe?’

Cited by 25 publications

References 96 publications

Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen suitable for allogeneic transplantation that maintains the graft versus malignancy effect

Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen suitable for allogeneic transplantation that maintains the graft versus malignancy effect

Caspase-8 dependent histone acetylation by a novel proteasome inhibitor, NPI-0052: a mechanism for synergy in leukemia cells

Bone marrow graft as a source of allogeneic hematopoietic stem cells in patients undergoing a reduced intensity conditioning regimen

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