Allogeneic hematopoietic stem cell transplantation in ovarian carcinoma: results of five patients

Bay, J.-O.; Fleury, J; Choufi, B; Tournilhac, Olivier; Vincent, Catherine; Bailly, C; Dauplat, J.; Viens, Patrice; Faucher, Catherine; Blaise, Didier

doi:10.1038/sj.bmt.1703609

Cited by 77 publications

(47 citation statements)

References 44 publications

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“…Two patients received additional donor lymphocyte infusions after transplant. Four of the patients developed acute or chronic graft-versus-host disease associated with tumor regression of at least 50% as assessed by CT scan or CA-125 levels [37]. Although initial results are provocative, further study is needed to determine whether this therapeutic strategy would be of benefit in patients with relapsed ovarian cancer.…”

Section: Strategies For Long-term Management Of Recurrent Diseasementioning

confidence: 99%

“…The effectiveness of donor lymphocyte infusion in inducing the remission of recurrent malignancy has been shown for almost all hematologic malignancies, although its efficacy varies across tumor subtypes [35]. More recently, investigators have begun to use this strategy in the treatment of solid tumors [36] including relapsed progressive ovarian cancer [37]. In an initial study, five patients with relapsed and chemoresistant ovarian cancer underwent alloHSCT from HLA identical siblings.…”

Section: Strategies For Long-term Management Of Recurrent Diseasementioning

confidence: 99%

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Future directions in the management of ovarian cancer

Disis

Rivkin²

2003

Hematology/Oncology Clinics of North America

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Section: Strategies For Long-term Management Of Recurrent Diseasementioning

confidence: 99%

Section: Strategies For Long-term Management Of Recurrent Diseasementioning

confidence: 99%

Future directions in the management of ovarian cancer

Disis

Rivkin²

2003

Hematology/Oncology Clinics of North America

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“…Three patients underwent a reduced regimen, which allocated response to GvOV rather than chemotherapy. 12 These preliminary results suggest that allo HCT for OC is a feasible procedure with a potential therapeutic benefit in patients who develop GvHD. However, the low patient number of previous studies did not allow evaluating the true benefit of allo HCT in OC.…”

mentioning

confidence: 92%

“…The median time to reach an absolute granulocyte count of 1.0 Â 10 9 /L was 14 days [range [11][12][13][14][15][16][17][18][19][20][21][22][23][24] and a platelet count of 20 Â 10 9 /L was 12 days [range 9-42]. Platelet counts did not fall below 20 Â 10 9 /L in 5 recipients (Table 1).…”

Section: Engraftment and Chimerismmentioning

confidence: 99%

Allogeneic hematopoietic stem cell transplantation in ovarian cancer—the EBMT experience

Bay¹,

Cabrespine-Faugeras²,

Tabrizi³

et al. 2010

Intl Journal of Cancer

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Although preliminary results suggest that allogeneic hematopoietic stem cell transplantation (allo HCT) for ovarian cancer (OC) is a feasible procedure, the low patient number in previous studies had limited ability to evaluate the true benefit of allo HCT in OC. This retrospective multicenter study included 30 patients with OC allografted between 1995 and 2005 to determine the outcome of patients with OC treated with allo HCT. Prior to allo HCT, patients were in complete response (n 5 1), partial response (n 5 7), stable disease (n 5 11) or had progressive disease (n 5 13). An objective response (OR) was observed in 50% (95% CI, 33-67) of patients. Three patients of responding patients had an objective response following the development of acute graft-versus-host disease (aGvHD). The cumulative incidence of chronic GvHD (cGVHD) was 34% (95% CI, 18-50). Transplant relative mortality rates were 7 and 20% on day 100 and 1 year, respectively. With a median follow-up of 74.5 months (range 16-148), median progression free survival (PFS) was 6 months and median overall survival (OS) was 10.4 months. Patients who developed cGvHD following allo HCT had a significant OS improvement compared to those who did not (17.6 months vs. 6.5 months, p 5 0.042). However, PFS was not similarly significantly improved in patients who developed cGvHD (12 months versus 3.7 months, p 5 0.81). Allo HCT in OC may lead to graft-versus-OC effects. Their clinical relevance remains to be shown.Ovarian cancer (OC), the fifth-leading cause of death for women in the United States and Europe, is the most deadly of the gynecologic malignancies. 1 Current systemic therapy consists of a combination of carboplatin and paclitaxel. Even after extensive surgery and chemotherapy, up to 50% of patients suffer from relapsing disease. Median overall survival (OS) for patients after recurrence is $2 years. 2 To improve outcome, high-dose chemotherapy regimens have been tried usually based on carboplatin combinations. These appear to delay relapse but have no influence on OS. [3][4][5] Allogeneic hematopoietic stem cell transplantation (allo HCT) is an effective therapy for many hematological malignancies. The therapeutic benefit of allogeneic transplantation relies not only on high-dose chemotherapy administered before transplantation but also is largely related to an immune-mediated graft-versus-leukemia effect, due to transplantation of the donor's immune system along with the hematopoietic tissue. Recent data from experimental animal models and from preliminary clinical experience suggest that a graft-versus-tumor effect, analogous to the graft-versusleukemia effect, may be generated against solid tumors such as renal cell cancer, breast cancer and OC. 6 Regarding OC, immunotherapy agents such as systemic or intraperitoneal interleukin-2 7-9 and adoptive transfer of tumor-infiltrating lymphocytes 10 have been used with success, testifying to the

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“…Other tumours including breast and ovarian cancers and germ cell tumours may also benefit from this approach (Bay et al, 2000(Bay et al, , 2002Pedrazzoli et al, 2002;Hanel et al, 2003;Donato et al, 2004), which is thought to exert its major antitumour effect via donor immune cells active against recipient malignancy (known as the graft-versus-tumour or GVT effect). The GVT effect makes the use of lymphocytes from HLA-identical donors preferable to the use of the patient's own lymphocytes for the purpose of generating cells for immunotherapy.…”

mentioning

confidence: 99%

Generation of tumour-specific cytotoxic T-cell clones from histocompatibility leucocyte antigen-identical siblings of patients with melanoma

Gottlieb

Lionello

et al. 2006

Br J Cancer

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Lymphodepletion and infusion of autologous expanded tumour-infiltrating lymphocytes is effective therapy for patients with malignant melanoma. Antitumour responses are likely to be mediated by HLA class I-and II-restricted immune responses directed at tumour antigens. We assessed whether the peripheral blood of normal HLA-matched siblings of patients with melanoma could be used to generate lymphocytes with antimelanoma activity for adoptive immunotherapy after allogeneic blood or marrow transplantation. Melanoma cell lines were derived from two donors and were used to stimulate the mononuclear cells of three HLAidentical siblings. CD4 þ clones dominated cultures. Of these, approximately half were directly cytotoxic towards recipient melanoma cells and secreted interferon-g in response to tumour stimulation. More than half of the noncytotoxic clones also secreted interferong after melanoma stimulation. No CD4 þ clones responded to stimulation with recipient haemopoietic cells. The majority of CD8 þ clones directly lysed recipient melanoma, but did not persist in long-term culture in vitro. No crossreactivity with recipient haemopoietic cells was observed. The antigenic target of one CD4 þ clone was determined to be an HLA-DR11-restricted MAGE-3 epitope. Antigenic targets of the remaining clones were not elucidated, but appeared to be restricted through a non-HLA-DR class II molecule. We conclude that the blood of allogeneic HLA-matched sibling donors contains melanoma-reactive lymphocyte precursors directed at tumour-associated antigens. Adoptive immunotherapy with unselected or ex vivo-stimulated donor lymphocytes after allogeneic stem cell transplantation has a rational basis for the treatment of malignant melanoma.

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Allogeneic hematopoietic stem cell transplantation in ovarian carcinoma: results of five patients

Cited by 77 publications

References 44 publications

Future directions in the management of ovarian cancer

Future directions in the management of ovarian cancer

Allogeneic hematopoietic stem cell transplantation in ovarian cancer—the EBMT experience

Generation of tumour-specific cytotoxic T-cell clones from histocompatibility leucocyte antigen-identical siblings of patients with melanoma

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