Acute GVHD prophylaxis with standard-dose, micro-dose or no MTX after fludarabine/melphalan conditioning

Chen, G L; Zhang, Y; Hahn, Theresa; Abrams, Scott I.; Ross, Maureen; Liu, H; McCarthy, Philip L.

doi:10.1038/bmt.2013.167

Cited by 9 publications

(5 citation statements)

References 32 publications

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“…Acute graft versus host disease (GvHD) prophylaxis was assigned as tacrolimus (TAC) only, TAC / mycophenolate mofetil (MMF), or a calcineurin inhibitor (TAC or cyclosporine) / methotrexate ± other (methylprednisolone of MMF). [6] TAC doses were adjusted to maintain blood levels of 5-10 ng/dl during the first 100 days then tapered off in the absence of GvHD by 6 months. MMF was discontinued at day +60 in the absence of GvHD.…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

Early versus Late Preemptive Allogeneic Hematopoietic Cell Transplantation for Relapsed or Refractory Acute Myeloid Leukemia

Chen

Liu

Zhang

et al. 2014

Biology of Blood and Marrow Transplantation

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Many patients with relapsed or refractory acute myeloid leukemia (AML) do not receive allogeneic hematopoietic cell transplant (alloHCT) because they are unable to achieve a complete remission (CR) after reinduction chemotherapy. Starting in January 2003, we prospectively assigned patients with AML with high risk clinical features to pre-emptive alloHCT (p-alloHCT) as soon as possible after reinduction chemotherapy. High risk clinical features were associated with poor response to chemotherapy: 1) primary induction failure (PIF), 2) second or greater relapse, and 3) first complete remission interval <6 months. We hypothesized that any residual disease would be maximally reduced at the time of transplant resulting in the best milieu and most lead time for developing a graft versus leukemia effect resulting in improved long term overall survival without excess toxicity. This is an analysis of the effect of transplant timing on p-alloHCT in 30 patients with high risk clinical features out of 156 consecutive AML patients referred for alloHCT. We compared early p-alloHCT within 4 weeks of reinduction chemotherapy prior to count recovery with late p-alloHCT 4 weeks after reinduction chemotherapy with count recovery. Overall and progression free survival (OS, PFS) at 2 years were not significantly different for early versus late palloHCT (OS 23% versus 33%, p>0.1; PFS 18% versus 22%, p>0.1). Day 100 and one year transplant related mortality were similar (33.3% versus 22.2%, p>0.1 and 44.4% versus 42.9%, p>0.1, respectively). Pre-emptive alloHCT allowed 30 patients to be transplanted who would normally not receive alloHCT. Clinical outcomes for early p-alloHCT are similar to those for late p-alloHCT without excess toxicity. Early p-alloHCT is a feasible alternative to late p-alloHCT for maximizing therapy of AML that is poorly responsive to induction chemotherapy.

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Section: Patients Materials and Methodsmentioning

confidence: 99%

Early versus Late Preemptive Allogeneic Hematopoietic Cell Transplantation for Relapsed or Refractory Acute Myeloid Leukemia

Chen

Liu

Zhang

et al. 2014

Biology of Blood and Marrow Transplantation

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“…Moreover, a systematic review of 11 studies showed increased incidence of grades III–IV acute GVHD for patients received MMF when compared to those received MTX for GVHD prophylaxis (RR 1.61, 95% CI 1.18–2.30) [ 23 ]. Chen G et al reported that tacrolimus (TAC)/MMF resulted in higher grades III–IV acute GVHD (49%) when compared with TAC/MTX (19%), TAC/micro-MTX/MMF (23%) following myeloablative conditioning (p<0.015) [ 25 – 26 ]. Also, this is comparable with other single-center NMA and MA studies which revealed that MMF-based GVHD prophylaxis increased incidences of acute GVHD (11.6–54.5%) when compared with other regimen [ 25 – 27 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of non-myeloablative conditioning regimens for lymphoproliferative disorders

Hong

Le‐Rademacher

Artz

et al. 2014

Bone Marrow Transplant

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Hematopoietic cell transplantation (HCT) with non-myeloablative conditioning (NMA) for lymphoproliferative diseases (LD) includes fludarabine with and without low-dose total body irradiation (TBI). Transplant outcomes were compared among patients ≥40 years with LD who received a HCT with TBI (N=382) and no-TBI (N=515) NMA from 2001 to 2011. The groups were comparable except for donor, graft, prophylaxis for graft-versus-host disease (GVHD), disease status and year of HCT. Cumulative incidences of grades II–IV GVHD at 100 days, were 29% and 20% (p=0.001), and chronic GVHD at 1 year were 54% and 44% (p=0.004) for TBI and no-TBI, respectively. Multivariate analysis of progression/relapse, treatment failure and mortality showed no outcome differences by conditioning. Full donor chimerism at day 100 was observed in 82% vs. 64% in the TBI and no-TBI groups, respectively (p=0.006). Subset of four most common conditioning/ GVHD prophylaxis combinations demonstrated higher rates of grades II–IV acute (p<0.001) and chronic GVHD (p<0.001) among recipients of TBI-mycophenolate mofetil (MMF) compared to other combinations. TBI-based NMA conditioning induces faster full donor chimerism but overall survival outcomes are comparable to no-TBI regimens. Combination of TBI and MMF are associated with higher rates of GVHD without impact on survival outcomes in patients with LD.

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“…Acute graft-versus-host disease (GvHD) prophylaxis consisted of tacrolimus, methotrexate, and mycophenolate as previously described [10]. Antibacterial, antifungal, and antiviral prophylaxes were given according to institutional standards.…”

Section: Supportive Carementioning

confidence: 99%

Reduced-Intensity Conditioning with Fludarabine, Melphalan, and Total Body Irradiation for Allogeneic Hematopoietic Cell Transplantation: The Effect of Increasing Melphalan Dose on Underlying Disease and Toxicity

Chen

Hahn

Wilding

et al. 2019

Biology of Blood and Marrow Transplantation

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A B S T R A C T Disease relapse and toxicity are the shortcomings of reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (alloHCT). We hypothesized that adding total body irradiation (TBI) to and decreasing melphalan (Mel) from a base RIC regimen of fludarabine (Flu) and Mel would increase cytoreduction and improve disease control while decreasing toxicity. We performed a phase II trial of Flu 160 mg/m 2 , Mel 50 mg/m 2 , and TBI 400 cGy (FluMelTBI-50, n = 61), followed by a second phase II trial of Flu 160 mg/m 2 , Mel 75 mg/m 2 , and TBI 400 cGy (FluMelTBI-75, n = 94) as RIC for alloHCT. Outcomes were compared with a contemporaneous cohort of 162 patients who received Flu 125 mg/m 2 and Mel 140 mg/m 2 . Eligibility criteria were equivalent for all 3 regimens. All patients were ineligible for myeloablative/intensive conditioning. The median (range) follow-up for all patients was 51 (15 to 103) months. Day 100 donor lymphoid chimerism and transplant-related mortality, neutrophil and platelet engraftment, acute and chronic graft versus host disease incidence, overall survival (OS), and progression-free survival (PFS) were equivalent between FluMel, FluMelTBI-50, and FluMelTBI-75. Stomatitis was decreased for FluMelTBI versus FluMel (P < .01). PFS for patients not in complete remission on alloHCT was improved for FluMelTBI-75 versus FluMel (P = .03). On multivariate analysis, OS (P = .05) and PFS (P = .05) were significantly improved for FluMelTBI-75 versus FluMel. FluMelTBI-75 is better tolerated than FluMel, with improved survival and disease control.

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Acute GVHD prophylaxis with standard-dose, micro-dose or no MTX after fludarabine/melphalan conditioning

Cited by 9 publications

References 32 publications

Early versus Late Preemptive Allogeneic Hematopoietic Cell Transplantation for Relapsed or Refractory Acute Myeloid Leukemia

Early versus Late Preemptive Allogeneic Hematopoietic Cell Transplantation for Relapsed or Refractory Acute Myeloid Leukemia

Comparison of non-myeloablative conditioning regimens for lymphoproliferative disorders

Reduced-Intensity Conditioning with Fludarabine, Melphalan, and Total Body Irradiation for Allogeneic Hematopoietic Cell Transplantation: The Effect of Increasing Melphalan Dose on Underlying Disease and Toxicity

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