Graft Versus Host Disease After Stem Cell Allotransplantation With Low-Dose Total Body Irradiation, Fludarabine, and Antithymocyte Globulin

Grosskreutz, Celia; Scigliano, Eileen; Osman, Keren; Isola, Luis

doi:10.1097/01.tp.0000279294.84222.61

Cited by 5 publications

(5 citation statements)

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“…This regimen was well tolerated and resulted in high rates of donor engraftment and low incidence of acute and chronic graft-versus-host disease (GVHD). These findings were later confirmed in a large cohort with a long follow-up period during which modest rates of acute (25%) and chronic (8%) GVHD were observed [30]. We currently report on a single-center cohort of 20 MM patients who received NST following a wide-variety of prior therapies with both related and unrelated donors.…”

Section: Introductionmentioning

confidence: 52%

“…In that series, the addition of ATG seemed to decrease the incidence of grade I or II GVHD compared with a similar regimen without ATG but did not seem to change the incidence of severe GVHD. A follow-up study in patients with various hematologic malignancies confirmed these results, as at a median follow-up of 862 days there was an overall incidence of a GVHD G I-II of only 15% and G III-IV of 18% for an overall incidence of 33% [30]. Other agents such as alemtuzumab have also been used for the same purpose [35].…”

Section: Discussionmentioning

confidence: 81%

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Non‐myeloablative conditioning and allogeneic transplantation for multiple myeloma

et al. 2010

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In multiple myeloma (MM), allogeneic stem cell transplantation (alloHCT) carries a lower relapse risk than autologous transplantation but a greater transplant-related mortality. Nonmyeloablative conditioning for allogeneic transplantation (NST) reduces transplant-related toxicity. Results are encouraging when used during first remission in low-risk patients, but less-so in relapsed or refractory disease. This is a single-center retrospective analysis of 20 previously treated MM patients who underwent NST from matched-related or matched-unrelated donors from 2000-2006. Median age was 52.7 years (37.2-68.0). Twenty-five percent had advanced or high-risk disease. Eleven still had active disease prior to NST. Conditioning was total body irradiation 200 cGy on a single fraction on day 25, followed by antithymocyte globulin (ATG) 1.5 mg/kg/day and fludarabine 30 mg/m 2 /day on days 24 to 22. All received immunosuppression, most commonly with oral mycofenylate mofetil and cyclosporine beginning on day 25. At day 100, 50% had achieved complete remission. Transplant-related mortality was 25%. Median overall survival (OS) was 21.2 months (0.6-901) and progression-free survival (PFS) 6.6 months (0.6-901). Both OS and PFS were 24% at 3 years. OS was significantly greater for patients with age <52 years (median 27 months vs. 7.9 months, P 5 0.031), and there was a trend toward greater OS for those with b2 microglobulin <2.5 mg/l (median 27 months vs. 7.7 months, P 5 0.08). Donor characteristics and Ig type had no significant effect on survival. These data suggest a benefit of NST in relapsed/refractory MM. Randomized trials must be performed to confirm and further qualify this benefit. Am. J. Hematol. 85:249-254, 2010. V V C 2010 Wiley-Liss, Inc. IntroductionMultiple Myeloma (MM) accounts for 1% of all cancers and 10% of all hematologic malignancies [1]. Melphalanbased high-dose chemotherapy with hematopoietic stem cell support increases the rate of complete remission (CR) and extends event-free and overall survival (EFS and OS) [2]. However, while autologous stem cell transplantation (ASCT) increases survival, it is not curative, and most patients relapse at a median of 3 years [3]. In contrast, allogeneic hematopoietic cell transplantation (alloHCT) carries a lower relapse risk [4], attributed to the graft-versus-myeloma (GVM) effect [5][6][7], but a greater transplantrelated mortality (TRM), estimated at 15 to 40% [8,9]. Currently, the transplant regimen of choice is nonmyeloablative allogeneic stem cell transplantation (NST), which aims to reduce transplant-related toxicity, while utilizing the GVM effect to control disease.There are now several publications on the benefit of alloHCT when planned after first reducing tumor burden by ASCT, particularly in the upfront setting [10]. In prospective trials, comparing first-line tandem ASCT-NST with double-ASCT, ASCT-NST yielded a much higher rate of CR (55 vs. 26%) and greater OS compared with the double-ASCT group in those with low-risk profiles [11]. However, ASCT-NST did n...

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Section: Introductionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 81%

Non‐myeloablative conditioning and allogeneic transplantation for multiple myeloma

et al. 2010

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“…MMF is most commonly combined with a calcineurin inhibitor for promotion of engraftment and prevention of GVHD after nonmyeloablative HCT. 1–3 MMF is rapidly hydrolyzed by esterase in the blood, gut wall, liver and tissues to MPA. 4,5 MPA is then glucuronidated hepatically and extrahepatically by UDP-glucuronosyl transferase (UGT) enzymes to the primary inactive metabolite, MPA glucuronide (MPAG).…”

Section: Introductionmentioning

confidence: 99%

Comparison of two mycophenolate mofetil dosing regimens after hematopoietic cell transplantation

Jacobson

El-Massah

Rogosheske

et al. 2009

Bone Marrow Transplant

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Mycophenolic acid (MPA)is the active component of mycophenolate mofetil (MMF). Low MPA exposure is associated with a higher incidence of acute GVHD and possibly worse engraftment. Therapeutic plasma targets have been proposed in hematopoietic cell transplantation (HCT), however, are difficult to achieve in adult patients with MMF doses of 2 g/day. Mycophenolate pharmaco-kinetics was prospectively studied in adults undergoing nonmyeloablative HCT who received MMF 3 g/day with CYA. The first 15 individuals received 1.5 g every 12 h and the second 15 received 1 g every 8 h. Sampling was performed in each patient with i.v. and oral administration. There were no differences in total or unbound MPA 24-h cumulative area under the curves (AUCs), concentrations at steady state (Css)or troughs between the two dosing regimens (all P>0.01). The previously proposed total MPA Css target of 3 μg/ml and trough ≥1 μ/ml were achieved in only 13–27% and 20–53% of patients, respectively, on 3 g/day. However, the 3 g/day regimens readily achieved satisfactory unbound 24-h cumulative AUC targets of 0.600 μg*h/ml in 87–100% of subjects. There appears to be no significant difference in daily MPA exposure when MMF of 3 g/day is divided into two or three equal doses.

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“…BU, Flu, ATG, and TBI 4 Gy provides a well-tolerated regimen with antileukemic activity comparable to that of other conventional myeloablative conditioning regimens [23]. Similarly, a series of 65 patients reported by Grosskreutz et al [24] suggested that the addition of ATG to TBI 2 Gy and Flu resulted in an improved transplantation outcome in patients with lymphoid malignancies.…”

Section: Discussionmentioning

confidence: 80%

Fludarabine, Antithymocyte Globulin, and Very Low-Dose Busulfan for Reduced-Intensity Conditioning before Allogeneic Stem Cell Transplantation in Patients with Lymphoid Malignancies

Malard

Cahu

Clavert

et al. 2011

Biology of Blood and Marrow Transplantation

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This retrospective report compared the results of a reduced-intensity conditioning (RIC) regimen including fludarabine (Flu), and very low-dose oral busulfan (BU) (4 mg/kg total dose) in combination with antithymocyte globulin (ATG) (Flu/ATG/BU) to the classical Flu and low-dose total body irradiation (TBI) (2 Gy) regimen (Flu/TBI) in patients with lymphoid malignancies. With a median follow-up of 42 months, the cumulative incidence of transplant-related mortality (TRM) was 22% in the Flu/ATG/BU group versus 41% in the Flu/TBI group (P = .09). Grade 3-4 acute graft-versus-host disease (aGVHD) and extensive chronic GVHD (cGVHD) incidents were 15% versus 44% (P = .006), and 12% versus 58% (P = .0003), in the Flu/ATG/BU group versus the Flu/TBI group, respectively. The Kaplan-Meier estimate of overall survival (OS) at 2 years was comparable between both groups (71%; 95% confidence interval [CI] 58%-86%, in the Flu/ATG/BU group vs 60%; 95% CI 44%-83%, in the Flu/TBI group, P = .20). The estimate of progression-free survival (PFS) was 63% (95% CI 50%-80%) in the Flu/ATG/BU group versus 52% (95% CI, 36%-76%) in the Flu/TBI group (P = .18), suggesting that reduced-intensity conditioning (RIC) based on Flu, very low-dose BU, and ATG has the potential to induce long-term remissions in patients with lymphoid malignancies.

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Graft Versus Host Disease After Stem Cell Allotransplantation With Low-Dose Total Body Irradiation, Fludarabine, and Antithymocyte Globulin

Abstract: The addition of ATG to TBI 200cGy and fludarabine resulted in a modest incidence of GVHD. The best transplant outcomes were observed in pts with lymphoid malignancies.

Cited by 5 publications

References 20 publications

Non‐myeloablative conditioning and allogeneic transplantation for multiple myeloma

Non‐myeloablative conditioning and allogeneic transplantation for multiple myeloma

Comparison of two mycophenolate mofetil dosing regimens after hematopoietic cell transplantation

Fludarabine, Antithymocyte Globulin, and Very Low-Dose Busulfan for Reduced-Intensity Conditioning before Allogeneic Stem Cell Transplantation in Patients with Lymphoid Malignancies

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