Matched unrelated donor bone marrow transplantation for the treatment of platinum refractory ovarian carcinoma: a case report

doi:10.1016/j.ygyno.2003.09.004

Gynecologic Oncology

Volume 92, Issue 1, January 2004, Pages 365-367

https://doi.org/10.1016/j.ygyno.2003.09.004 Get rights and content

Abstract

Background. We are reporting on a case of platinum-refractory low-grade ovarian cancer responding to treatment with an allogeneic bone marrow transplantation from an unrelated donor.

Case. The 37-year-old patient received a preparative regimen consisting of fludarabine 25 mg/m² on days −6, −5, −4, −3 and −2, melphalan 70 mg/m² on days −3 and −2, and thymoglobulin 2 mg/kg on days −3, −2 and −1. An unrelated HLA-compatible bone marrow was infused on day 0. Graft-versus-host disease prophylaxis consisted of tacrolimus and methotrexate. The patient demonstrated complete donor chimerism. Serial CT scans of the abdomen and pelvis over the following 15 months showed a slow regression of the malignant lesion.

Conclusion. Engraftment of an unrelated donor marrow was achieved in a patient with ovarian cancer and induced a tumor response. This suggests the presence of a graft-versus-tumor effect in ovarian cancer. Further study is underway.

Introduction

Platinum-refractory ovarian cancer is associated with an overall poor prognosis and long-lasting remissions are rarely seen [1]. Matched unrelated bone marrow grafts have been used extensively for the treatment of hematological malignancies. The presence of a graft-versus-tumor effect has been well documented in that setting [2]. We are reporting a case of platinum-refractory low-grade ovarian carcinoma treated with a matched unrelated bone marrow transplantation.

Section snippets

Case report

A 37-year-old female was originally diagnosed with stage IIIc low-grade papillary serous carcinoma of the ovary in October 2000. She underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy and optimal tumor reductive surgery followed by six cycles of paclitaxel and carboplatin finishing in February 2001. One month later, in March 2001, a computerized tomography of the abdomen and pelvis revealed a new pelvic lesion, which was biopsy-proven to be ovarian cancer (Fig. 1). This

Discussion

Allogeneic transplantation was originally recognized as a potentially curative treatment for patients with hematological malignancies. In this patient population, it has been demonstrated that the presence of graft-versus-host disease is associated with fewer relapses, leading investigators to the concept of a graft-versus-leukemia effect [2]. Furthermore, post-transplantation donor lymphocyte infusions (DLI) can promote the graft-versus-leukemia effect and in many circumstances induce

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Melphalan and purine analog-containing preparative regimens: reduced intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation
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Cited by (6)

Synergistic cytotoxicity of interferonα-2b and interleukin-2 in combination with PBMC against ovarian cancer: Development of an experimental model for cellular therapy
2009, Gynecologic Oncology
Citation Excerpt :
Tumor regression was seen in all four patients, which was associated with graft versus host disease (GVHD). Recently, Donato et al. [5] used a non-myeloablative allogeneic HSCT regimen to treat a platinum refractory OC patient. She did not develop any chronic GVHD and showed a continued slow regression of her tumor over a period of 15-months.
Current therapies for ovarian cancer (OC) patients have a modest impact on long-term survival justifying the need for novel treatment strategies. We developed in vitro and in vivo systems to test the effects of cytokines in combination with peripheral blood mononuclear cells (PBMC) on OC cells.
Two OC cell-lines were transfected with a plasmid encoding Red Fluorescent Protein (SKOV3-RFP and CAR3-RFP). Proliferation of these lines in the presence of cytokines alone and in combination was assayed. Cytotoxicity of SKOV3-RFP cells mediated by PBMC and cytokines was determined by lactate dehydrogenase release. Mice were injected intraperitoneally (IP) with SKOV3-RFP cells; solid tumor and ascitic fluid were collected, analyzed, and cell lines were established. Tumor-derived cell lines were re-injected to produce a more tumorigenic line.
IFNα-2b showed an inhibitory effect on OC cell proliferation. The remaining cytokines, either alone or in combination, showed no significant effect. PBMC in combination with IL-2 showed clear dose-dependent cytotoxicity against SKOV3-RFP. IFNα-2b had a synergistic effect with IL-2 and PBMC increasing the cytotoxicity by an average of 20%. Using an animal model, SKOV3-RFP cells continue to express RFP when harvested from the peritoneum and are more tumorigenic when re-injected into mice.
These observations justify the use of IL-2, IFNα-2b, and PBMC in a xenograph animal model of OC to determine if combination cytokine and cellular therapy has an anti-tumor effect in vivo. This approach may prove useful as an in vivo system of IP cytokines administered in combination with cellular therapy.
Rapid expansion of tumor-reactive cells from HLA-matched siblings for a adoptive immunotherapy of melanoma
2007, Cytotherapy
Citation Excerpt :
Allogeneic blood or marrow transplantation is emerging as a promising treatment in patients with some solid tumors, including renal cell carcinoma, breast and ovarian cancers and germ cell tumors [1–7].
Administration of expanded tumor-infiltrating lymphocytes in association with lymphodepleting chemotherapy is effective in some patients with advanced malignant melanoma. However, obtaining lymphocytes and subsequent expansion is labor intensive, making it impractical for broad clinical application. Allogeneic transplantation may have anti-melanoma efficacy because of a graft vs. tumor effect. The disappointing tumor control observed post-transplant suggests that adoptive immunotherapy using melanoma-reactive cells will be essential for sustained responses.
Melanoma cell lines were grown from two patients with advanced disease. High-level CD80 and CD86 expression was obtained in the tumor lines using a retroviral vector for gene transfer. Transduced melanoma and controls were cultured with mononuclear cells from HLA-identical sibling donors.
Expression of CD80 and CD86, particularly the former, promoted marked expansion of lymphocytes from HLA-matched sibling donors. Proliferation of up to 300-fold after 4 weeks of culture was observed. Lymphocytes from cultures stimulated with CD80 demonstrated cytotoxicity against recipient-untransfected melanoma (45–75% specific lysis at an E:T ratio of 50:1). Although expanded lymphocytes were predominantly CD4⁺, cytotoxicity was greatest in the numerically smaller CD8⁺ subpopulation. Both CD4⁺ and CD8⁺ cells secreted IFN-γ (but not IL-4) on exposure to untransduced stimulator melanoma cells.
Our strategy generates a large number of melanoma-reactive lymphocytes from HLA-identical siblings using a 4-week culture strategy. Lymphocytes expanded in this way offer an alternative to tumor-infiltrating lymphocytes for allogeneic cellular immunotherapy after stem cell transplantation in young patients.
Expression of FK506 binding protein 65 (FKBP65) is decreased in epithelial ovarian cancer cells compared to benign tumor cells and to ovarian epithelium
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Immunotherapy for epithelial ovarian cancer - immunological background, critical review of methods and future perspectives
2010, Current Immunology Reviews
Generation of tumour-specific cytotoxic T-cell clones from histocompatibility leucocyte antigen-identical siblings of patients with melanoma
2006, British Journal of Cancer
Stem cell-based treatments for gynecological solid tumors
2005, European Review for Medical and Pharmacological Sciences

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Case ReportMatched unrelated donor bone marrow transplantation for the treatment of platinum refractory ovarian carcinoma: a case report

Abstract

Introduction

Section snippets

Case report

Discussion

Gynecol. Oncol.

Blood

Blood

Case Report
Matched unrelated donor bone marrow transplantation for the treatment of platinum refractory ovarian carcinoma: a case report