6: Post-transplantation high-dose cyclophosphamide (Cy) is effective single agent GVHD prophylaxis that permits prompt immune reconstitution after myeloablative HLA matched related and unrelated bone marrow transplantation (BMT)

Luznik, Leo; Fuchs, Ephraim J.; Chen, A.R.; Kaup, Michele; Bright, Emilie C.; Bolaños-Meade, Javier; Hess, Allan D.; Jones, Richard J.

doi:10.1016/j.bbmt.2006.12.008

Cited by 19 publications

(18 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A preliminary analysis of blood concentrations of CD4 ϩ and CD8 ϩ T lymphocytes compares favorably with levels seen after T cell-replete bone marrow transplantation and GVHD prophylaxis with cyclosporine and methotrexate (data not shown). 48,49 The low overall incidence of infection-related complications is consistent with favorable immunologic recovery after posttransplantation cyclophosphamide. It is possible that the timing of the high-dose, posttransplantation cyclophosphamide results in selective killing of activated alloreactive T cells while sparing resting T cells specific for infectious agents.…”

Section: Discussionmentioning

confidence: 76%

High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease

Luznik

Bolaños-Meade

Zahurak

et al. 2010

Blood

362

307

View full text Add to dashboard Cite

Because of its potent immunosuppressive yet stem cell-sparing activity, highdose cyclophosphamide was tested as sole prophylaxis of graft-versus-host disease (GVHD) after myeloablative allogeneic bone marrow transplantation (alloBMT). We treated 117 patients (median age, 50 years; range, 21-66 years) with advanced hematologic malignancies; 78 had human leukocyte antigen (HLA)-matched related donors and 39 had HLAmatched unrelated donors. All patients received conventional myeloablation with busulfan/cyclophosphamide (BuCy) and T cell-replete bone marrow followed by 50 mg/kg/d of cyclophosphamide on days 3 and 4 after transplantation. The incidences of acute grades II through IV and grades III through IV GVHD for all patients were 43% and 10%, respectively. The nonrelapse mortality at day 100 and 2 years after transplantation were 9% and 17%, respectively. The actuarial overall survival and event-free survivals at 2 years after transplantation were 55% and 39%, respectively, for all patients and 63% and 54%, respectively, for patients who underwent transplantation while in remission.

show abstract

Section: Discussionmentioning

confidence: 76%

High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease

Luznik

Bolaños-Meade

Zahurak

et al. 2010

Blood

362

307

View full text Add to dashboard Cite

show abstract

“…30 However, the costs of sirolimus and its monitoring, as well as the trend toward more endothelial injury syndromes, may counterbalance these advantages. Other GVHD regimens that either lower methotrexate dose 31 or replace methotrexate with other agents, 32,33 have either not yet been tested in prospective trials or are associated with increased risks of GVHD.…”

Section: Org Frommentioning

confidence: 99%

“…There was no difference in the incidence of malignant disease relapse in the 2 study arms (28% [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] (Figure 4A-B). In multivariable analysis, advanced disease status at transplantation predicted relapse (P 5 .026), disease-free survival (P 5 .017), and overall survival (P 5 .034).…”

Section: Disease Relapse and Survivalmentioning

confidence: 99%

Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT

Cutler

Logan

Nakamura

et al. 2014

Blood

190

139

View full text Add to dashboard Cite

• Tac/Sir prophylaxis provides equivalent GVHD-free survival when compared with Tac/Mtx in MRD transplantation.• Tac/Sir is associated with more rapid engraftment and reduced oropharyngeal mucositis after MRD transplantation.Grades 2-4 acute graft-versus-host disease (GVHD) occurs in approximately 35% of matched, related donor (MRD) allogeneic hematopoietic cell transplantation (HCT) recipients. We sought to determine if the combination of tacrolimus and sirolimus (Tac/Sir) was more effective than tacrolimus and methotrexate (Tac/Mtx) in preventing acute GVHD and early mortality after allogeneic MRD HCT in a phase 3, multicenter trial. The primary end point of the trial was to compare 114-day grades 2-4 acute GVHD-free survival using an intention-to-treat analysis of 304 randomized subjects. There was no difference in the probability of day 114 grades 2-4 acute GVHD-free survival (67% vs 62%, P 5 .38). Grades 2-4 GVHD was similar in the Tac/Sir and Tac/Mtx arms (26% vs 34%, P 5 .48). Neutrophil and platelet engraftment were more rapid in the Tac/Sir arm (14 vs 16 days, P < .001; 16 vs 19 days, P 5 .03). Oropharyngeal mucositis was less severe in the Tac/Sir arm (peak Oral Mucositis Assessment Scale score 0.70 vs 0.96, P < .001), but otherwise toxicity was similar. Chronic GVHD, relapse-free survival, and overall survival at 2 years were no different between study arms (53% vs 45%, P 5 .06; 53% vs 54%, P 5 .77; and 59% vs 63%, P 5 .36). Based on similar long-term outcomes, more rapid engraftment, and less oropharyngeal mucositis, the combination of Tac/Sir is an acceptable alternative to

show abstract

“…In this sense, the cyclophosphamide-using cell therapy may be a choice of treatment because the lower levels of mixed chimerism can reduce the risk of GVHD (35,36). Recently, similar posttransplant administration of cyclophosphamide has been applied to clinical nonmyeloablative allogeneic SCT for hematologic malignancies (37,38). We hope that the concept that a high level of chimerism may not be essential for the in vivo antitumor effect against solid cancer in our current study will help reduce the risk of GVHD during the course of nonmyeloablative allogeneic SCT for the treatment of patients with advanced RCC.…”

Section: Discussionmentioning

confidence: 99%

Posttransplant Administration of Cyclophosphamide and Donor Lymphocyte Infusion Induces Potent Antitumor Immunity to Solid Tumor

Eto¹,

Kamiryo

Takeuchi

et al. 2008

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Nonmyeloablative allogeneic stem cell transplantation (SCT) has been increasingly used for the treatment of hematologic and solid malignancies, and mature donor T cells are considered to be the main effectors of the graft-versus-tumor (GVT) activity. However, the association between degree of donor chimerism and intensity of GVT effects has not been fully elucidated. We recently proposed a unique nonmyeloablative cell therapy using posttransplant cyclophosphamide and donor lymphocyte infusion, by which a significant antitumor effect against murine renal cell carcinoma, RENCA, was induced, although the level of mixed chimerism was relatively low. In this study, we attempted to clarify a role of chimerism for in vivo antitumor effects on GVTeffects in radiation-associated nonmyeloablative SCT. Experimental Design: We assessed antitumor effects on RENCA tumors and the degree of donor chimerism after several doses of irradiation followed by allogeneic SCTand compared the results with those of cyclophosphamide-based cell therapy. Results: Allogeneic SCT following sublethal irradiation (6 Gy) induced almost complete donor chimerism, whereas cyclophosphamide-based cell therapy produced low levels of donor chimerism. Nonetheless, GVTactivity was much more potent in cyclophosphamide-based cell therapy than irradiation-conditioned SCT. Furthermore, cyclophosphamide-conditioned SCT induced more potent immune reconstitution with less severe graft-versus-host disease than irradiationconditioned SCT. Conclusions: Our results indicate that a high level of chimerism is not essential for the in vivo antitumor effect of nonmyeloablative allogeneic cell therapy against solid tumor and that the recovery of peripheral lymphocytes after the initial immunosuppression might be a critical event for the elicitation of in vivo antitumor effects of that treatment modality.

show abstract

6: Post-transplantation high-dose cyclophosphamide (Cy) is effective single agent GVHD prophylaxis that permits prompt immune reconstitution after myeloablative HLA matched related and unrelated bone marrow transplantation (BMT)

Cited by 19 publications

References 0 publications

High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease

High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease

Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT

Posttransplant Administration of Cyclophosphamide and Donor Lymphocyte Infusion Induces Potent Antitumor Immunity to Solid Tumor

Contact Info

Product

Resources

About