High-dose chemotherapy with hematopoietic rescue in patients with stage III to IV ovarian cancer: long-term results.

Legros, Michel; Dauplat, J.; Fleury, J; Curé, Hervé; F, Suzanne; Chassagne, J; Bay, Jacques Olivier; Sol, Chang Hyo; Canis, Michel; P, Condat; Choufi, Bachra; Tavernier, F; Glenat, C; Chollet, Philippe; Plagne, R

doi:10.1200/jco.1997.15.4.1302

Cited by 91 publications

(71 citation statements)

References 15 publications

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Section: Case Reportmentioning

confidence: 99%

“…According to our experience in autologous transplantation, the prognosis of the patient was poor and intensive chemotherapy followed by autologous peripheral blood stem cell transplantation was unlikely to be able to cure the disease. 5 Because of the good performance status of the patient, a bone marrow allograft was proposed with an HLA-identical, sex mismatched adult sibling.Before the allograft procedure the patient presented with abdominal tumor nodules, a progression of pulmonary metastatic lesions and the elevation of CA125 (169 U). The conditioning regimen consisted of myleran 4 mg/kg daily for 4 consecutive days and cyclophophamide 50 mg/kg daily for 4 consecutive days.…”

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confidence: 99%

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Potential allogeneic graft-versus-tumor effect in a patient with ovarian cancer

Bay¹,

Choufi²,

Pomel

et al. 2000

Bone Marrow Transplant

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Summary:A 33-year-old woman developed progressive ovarian cancer resistant to classical chemotherapy agents. We performed a bone marrow allograft after a myeloablative regimen. During hematological recovery, she developed acute graft-versus-host disease (GVHD). From this time her tumor diminished progressively. One year post transplant she has limited chronic liver GVHD and is still free of disease. The complete remission of advanced ovarian cancer was probably related to the GVHD which might therefore provide a new treatment option for this disease. Bone Marrow Transplantation (2000) 25, 681-682. Keywords: ovarian cancer; allograft transplantation; graft-versus-host diseaseThe graft-versus-leukemia (GVL) effect has been reported in hematological malignancies after allogeneic treatments. This immunological effect has been recently described in patients with solid tumors after allogeneic bone marrow transplantation (graft-versus-tumor effect). 1-3 Ovarian carcinoma represents an additional target for this type of immunotherapy. 4 In this context, we report the first case of a patient who achieved a complete response after allogeneic bone marrow transplantation for ovarian cancer. Case reportA 33-year-old woman was diagnosed with ovarian cancer in May 1995. She presented with a serous papillary adenocarcinoma stage III C (FIGO). A partial remission was achieved after six chemotherapy courses (PAC: doxorubicin 240 mg total dose received (TDR), cyclophosphamide 6400 mg TDR, cisplatin 720 mg TDR). After this first-line chemotherapy complete surgery was performed, followed by intraperitoneal chemotherapy (doxorubicin 5 mg and cisplatin 25 mg once daily for 5 consecutive days). She relapsed 10 months later in September 1997. At this time she presented with an occlusive syndrome, subcutaneous tumor nodules and pulmonary metastases. This relapse was confirmed by an elevation of CA125 (164 U) and tomodensitometric examination. She was treated with seven courses of paclitaxel 1765 mg TDR and carboplatin 3140 mg TDR. A transitory partial response was obtained after four courses, but was followed by disease progression. According to our experience in autologous transplantation, the prognosis of the patient was poor and intensive chemotherapy followed by autologous peripheral blood stem cell transplantation was unlikely to be able to cure the disease. 5 Because of the good performance status of the patient, a bone marrow allograft was proposed with an HLA-identical, sex mismatched adult sibling.Before the allograft procedure the patient presented with abdominal tumor nodules, a progression of pulmonary metastatic lesions and the elevation of CA125 (169 U). The conditioning regimen consisted of myleran 4 mg/kg daily for 4 consecutive days and cyclophophamide 50 mg/kg daily for 4 consecutive days. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. Complete hematological recovery was obtained, with full cytogenetic chimerism at day 30. Acute grade III GVHD (Glucksberg) involving the skin and...

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Section: Case Reportmentioning

confidence: 99%

mentioning

confidence: 99%

Potential allogeneic graft-versus-tumor effect in a patient with ovarian cancer

Bay¹,

Choufi²,

Pomel

et al. 2000

Bone Marrow Transplant

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“…Highdose chemotherapy improved PFS but had failed to improve OS. [3][4][5] New drugs such as topotecan lead to a biological response but induced severe hematologic toxicities. 17 Since Child et al had demonstrated in kidney cancer a GvT effect, the first potential evidence of allogeneic antitumoral response in solid tumors, 18 allo HCT was the next logical step.…”

Section: Discussionmentioning

confidence: 99%

“…Among these patients, 1 was in CR at the time of allo HCT, while 7 were in PR, 11 in SD and 13 had PD. The median number of prior chemotherapy lines was 3 [range [2][3][4][5][6][7]. Seventeen donors were female (53%) with a median age of 46 years (range 27-65; Table 1).…”

Section: Patients' and Donors' Characteristicsmentioning

confidence: 99%

“…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.…”

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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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A multicenter randomized phase II trial of granulocyte-colony stimulating factor-supported, platinum-based chemotherapy with flexible midcycle cisplatin administration in patients with advanced ovarian carcinoma

Hidalgo

Mendiola

López‐Vega

et al. 1998

Cancer

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BACKGROUND The purpose of this study was to analyze whether the addition of granulocyte‐colony stimulating factor (G‐CSF) to platinum‐based combination chemotherapy could increase platinum dose intensity and response rates and decrease hematologic toxicity in patients with advanced epithelial ovarian carcinoma. METHODS Patients with untreated advanced ovarian carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stage IIC‐IV) were treated after maximum debulking surgery with cyclophosphamide, 750 mg/m2, and carboplatin, 350 mg/m2, on Day 1 plus cisplatin, 75 mg/m2, on Day 14 when clinically indicated (adequate bone marrow and renal function). Patients were randomized to receive chemotherapy alone (Arm A) or chemotherapy supported with G‐CSF (5 μg/kg subcutaneously on Days 2‐13; Arm B). RESULTS Between November 1993 and April 1995, 80 patients were included. Seventy‐eight patients were evaluable for dose intensity calculations. Both groups were well matched with regard to age, Eastern Cooperative Oncology Group performance status, histopathologic subtype, tumor grade, FIGO stage, and residual tumor after surgery. The dose intensities calculated in mg/m2/week for cyclophosphamide and carboplatin were similar in both groups; however, the dose intensity of cisplatin was higher in Arm B (5.7 mg/m2 vs. 10.3 mg/m2). The occurrence of Common Toxicity Criteria Grade 3‐4 neutropenia was less common in the G‐CSF arm (55% vs. 7.7%). Response rates (52% vs. 68%) and pathologic complete responses (32% vs. 25%) were similar in both groups. CONCLUSIONS The addition of G‐CSF to this platinum‐based chemotherapy regimen in patients with advanced ovarian carcinoma resulted in a modest increment in platinum dose intensity and appeared to reduce the incidence of Grade 3‐4 neutropenia. Cancer 1998;83:719‐725. © 1998 American Cancer Society.

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High-dose chemotherapy with hematopoietic rescue in patients with stage III to IV ovarian cancer: long-term results.

Cited by 91 publications

References 15 publications

Potential allogeneic graft-versus-tumor effect in a patient with ovarian cancer

Potential allogeneic graft-versus-tumor effect in a patient with ovarian cancer

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

A multicenter randomized phase II trial of granulocyte-colony stimulating factor-supported, platinum-based chemotherapy with flexible midcycle cisplatin administration in patients with advanced ovarian carcinoma

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