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

ABSTRACT Allogeneic hematopoietic stem cell transplantation is often used to treat hematologic malignancies. The efficacy of this procedure is due to both myeloablative conditioning and

graft-versus-leukemia (GVL). However, the disadvantages of allogeneic transplantation include graft-versus-host disease (GVHD), relapse from the original tumor, and patient susceptibility to

opportunistic infections. Lately, allogeneic transplantation has been developed to treat solid tumors, with the expectation that graft-versus-tumor (GVT), like GVL, will have a significant

anti-tumor effect. This effect has been demonstrated in renal carcinomas, and with less evidence in breast cancers. Five patients with malignant ovarian tumors resistant to chemotherapy

underwent allogeneic transplantation, four from bone marrow, and one from peripheral blood stem cells. All donors were HLA-identical siblings. One patient received a myeloablative

conditioning regimen, while the other four received a non-myeloablative regimen. Two patients received donor lymphocyte infusions (DLI). Four of the patients presented with acute or chronic

GVHD associated with tumor regression of at least 50%. These tumor regressions were measured by CA-125 levels and CT scans. The fifth patient died of rapid progression just after

transplantation. Of the four transplantation survivors, three received a non-myeloablative regimen which did not seem to reduce treatment effectiveness. While it did reduce toxicity, one of

these patients died of GVHD after 127 days. DLI was administered to two patients. These infusions seemed to promote GVHD which was able to control disease progression for one patient and had

no apparent effect on the other. Allograft of hematopoietic stem cells might be of interest in ovarian cancer. The results in one patient also suggest that DLI may be an effective

immunotherapy, although doses and timing need to be determined. The number of cases presented is small, however, and clinical experience on a larger scale will be required to determine the

real clinical efficacy of graft versus cancerous ovarian cells. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS

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access 29 January 2021 REFERENCES * Smith JP, Rutledge F, Wharton JT . Chemotherapy in ovarian cancer. New approaches to treatment _Cancer_ 1972 30: 1565 1571 Article  CAS  PubMed  Google

Scholar  * Tobias JS, Griffiths CT . Management of ovarian carcinoma. Current concepts and future prospects _New Engl J Med_ 1976 294: 881 882 Article  Google Scholar  * Thigpen JT,

Bertelsen K, Eisenhauer EA _et al_. Long-term follow-up of patients with advanced ovarian carcinoma treated with chemotherapy _Ann Oncol_ 1993 4: (Suppl. 4) S35 S40 Article  Google Scholar 

* Platz CE, Benda JA . Female genital tract cancer _Cancer_ 1995 75: (Suppl. 1) 270 294 Article  CAS  PubMed  Google Scholar  * Thigpen T, Vance R, Puneky L _et al_. Chemotherapy in advanced

ovarian carcinoma: current standards of care based on randomized trials _Gynecol Oncol_ 1994 55: S97 S107 Article  CAS  PubMed  Google Scholar  * Francis P, Schneider J, Hann L _et al_.

Phase II trial of docetaxel in patients with platinum-refractory advanced ovarian cancer _J Clin Oncol_ 1994 12: 2301 2308 Article  CAS  PubMed  Google Scholar  * McGuire WP, Hoskins WJ,

Brady MF _et al_. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer _New Engl J Med_ 1996 334: 1 6 Article  CAS 

PubMed  Google Scholar  * Stiff PJ, Bayer R, Kerger C _et al_. High-dose chemotherapy with autologous transplantation for persistent/relapsed ovarian cancer: a multivariate analysis of

survival for 100 consecutively treated patients _J Clin Oncol_ 1997 15: 1291 1293 Article  Google Scholar  * Legros M, Dauplat J, Fleury J _et al_. High-dose chemotherapy with hematopoietic

rescue in patients with stage III to IV ovarian cancer: long-term results _J Clin Oncol_ 1997 15: 1302 1308 Article  CAS  PubMed  Google Scholar  * Edwards RP, Gooding W, Lembersky BC _et

al_. Comparison of toxicity and survival following intraperitoneal recombinant interleukin-2 for persistent ovarian cancer after platinum: 24-hour _versus_ 7-day infusion _J Clin Oncol_ 1997

15: 3399 3407 Article  CAS  PubMed  Google Scholar  * Freedman RS, Kudelka AP, Kavanagh JJ _et al_. Clinical and biological effects of intraperitoneal injections of recombinant

interferon-gamma and recombinant interleukin 2 with or without tumor-infiltrating lymphocytes in patients with ovarian or peritoneal carcinoma _Clin Cancer Res_ 2000 6: 2268 2278 CAS  PubMed

  Google Scholar  * Thomas ED, Strob R, Clift RA _et al_. Bone-marrow transplantation _New Engl J Med_ 1975 292: 895 902 Article  CAS  PubMed  Google Scholar  * Weiden PL, Flournoy N, Thomas

ED _et al_. Anti-leukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts _New Engl J Med_ 1979 300: 1068 1073 Article  CAS  PubMed  Google Scholar  *

Ratanatharathorn V, Uberti J, Karanes C _et al_. Prospective comparative trial of autologous versus allogeneic bone marrow transplantation in patients with non-Hodgkin's lymphoma

_Blood_ 1994 84: 1050 1055 CAS  PubMed  Google Scholar  * Gorin NC, Lebopin M, Fouillard L _et al_. Retrospective evaluation of autologous bone marrow transplantation _vs_ allogeneic bone

marrow transplantation from an HLA identical related donor in acute myelocytic leukemia _Bone Marrow Transplant_ 1996 18: 111 117 CAS  PubMed  Google Scholar  * Sullivan K, Weiden P, Storb R

_et al_. Influence of chronic graft-versus-disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia _Blood_

1989 73: 1720 1728 CAS  PubMed  Google Scholar  * Weiden P, Sullivan K, Flournoy N _et al_. Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after

allogeneic marrow transplantation _New Engl J Med_ 1981 304: 1529 1533 Article  CAS  PubMed  Google Scholar  * Horowitz MM, Gale RP, Sondel PM _et al_. Graft-versus-leukemia reactions after

bone marrow transplantation _Blood_ 1990 75: 555 562 CAS  PubMed  Google Scholar  * Maraninchi D, Gluckman E, Blaise D _et al_. Impact of T-cell depletion on outcome of allogeneic

bone-marrow transplantation for standard-risk leukaemias _Lancet_ 1987 2: 175 178 Article  CAS  PubMed  Google Scholar  * Goldman J, Gale R, Horowitz M _et al_. Bone marrow transplantation

for chronic myelogenous leukemia in chronic phase. Increased risk for relapse associated with T-cell depletion _Ann Intern Med_ 1988 108: 806 814 Article  CAS  PubMed  Google Scholar  *

Blaise D, Gravis G, Maraninchi D . Long-term follow-up of T-cell depletion for bone marrow transplantation _Lancet_ 1993 341: 51 52 Article  CAS  PubMed  Google Scholar  * Kolb H,

Schattenberg A, Goldman J _et al_. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients _Blood_ 1995 86: 2041 2050 CAS  PubMed  Google Scholar  * Giralt

S, Estey E, Albitar M _et al_. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative

therapy _Blood_ 1997 89: 4531 4536 CAS  PubMed  Google Scholar  * Slavin S, Nagler A, Naparstek E _et al_. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to

conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases _Blood_ 1998 91: 756 763 CAS  PubMed  Google Scholar 

* Childs R, Clave E, Contentin N _et al_. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune

responses _Blood_ 1999 94: 3234 3241 CAS  PubMed  Google Scholar  * Childs R, Epperson D, Bahceci E _et al_. Molecular remission of chronic myeloid leukaemia following a non-myeloablative

allogeneic peripheral blood stem cell transplant: _in vivo_ and _in vitro_ evidence for a graft-versus-leukaemia effect _Br J Haematol_ 1999 107: 396 400 Article  CAS  PubMed  Google Scholar

  * Ben-Yosef R, Or R, Nagler A _et al_. Graft-versus-tumour and graft-versus-leukaemia effect in patient with concurrent breast cancer and acute myelocytic leukaemia _Lancet_ 1996 348: 1242

1243 Article  CAS  PubMed  Google Scholar  * Eibl B, Schwaighofer H, Nachbaur D _et al_. Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and

allogeneic bone marrow transplantation for breast cancer _Blood_ 1996 88: 1501 1508 CAS  PubMed  Google Scholar  * Ueno N, Rondon G, Mirza NQ _et al_. Allogeneic peripheral-blood

progenitor-cell transplantation for poor-risk patients with metastatic breast cancer _J Clin Oncol_ 1998 16: 986 993 Article  CAS  PubMed  Google Scholar  * Childs R, Chernoff A, Contentin N

_et al_. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation _New Engl J Med_ 2000 343: 750 758 Article  CAS  PubMed 

Google Scholar  * Bay J-O, Choufi B, Pomel C _et al_. Potential allogeneic graft-versus-tumor effect in a patient with ovarian cancer _Bone Marrow Transplant_ 2000 25: 681 682 Article  CAS 

PubMed  Google Scholar  * Deeg HJ, Henslee-Downey PJ . Management of acute graft-versus-host disease _Bone Marrow Transplant_ 1990 6: 1 8 CAS  PubMed  Google Scholar  * Cahn JY, Bordigoni P,

Tiberghien P _et al_. Treatment of acute graft-versus-host disease with methylprednisolone and cyclosporine with or without an anti-interleukin-2 receptor monoclonal antibody. A multicenter

phase III study _Transplantation_ 1995 60: 939 942 Article  CAS  PubMed  Google Scholar  * Glucksberg H, Storb R, Fefer A _et al_. Clinical manifestations of graft-versus-host disease in

human recipients of marrow from HL-A-matched sibling donors _Transplantation_ 1974 18: 295 304 Article  CAS  PubMed  Google Scholar  * Armitage JO . Bone marrow transplantation _New Engl J

Med_ 1994 330: 827 838 Article  CAS  PubMed  Google Scholar  * Rill DR, Santana VM, Roberts WM _et al_. Direct demonstration that autologous bone marrow transplantation for solid tumors can

return a multiplicity of tumorigenic cells _Blood_ 1994 84: 380 383 CAS  PubMed  Google Scholar  * Storb R, Yu C, Zaucha JM _et al_. Stable mixed hematopoietic chimerism in dogs given donor

antigen, CTLA4Ig, and 100 cGy total body irradiation before and pharmacologic immunosuppression after marrow transplant _Blood_ 1999 94: 2523 2529 CAS  PubMed  Google Scholar  * Sandmaier

BM, McSweeney P, Yu C _et al_. Nonmyeloablative transplants: preclinical and clinical results _Semin Oncol_ 2000 2(SUPPL. 5): 78 81 Google Scholar  * Dansey RD, Baynes RD . Nonablative

allogeneic hematopoietic stem cell transplantation _Curr Opin Oncol_ 2001 13: 27 32 Article  CAS  PubMed  Google Scholar  * Michallet M, Bilger K, Garban F _et al_. Allogeneic hematopoietic

stem-cell transplantation after nonmyeloablative preparative regimens: impact of pretransplantation and posttransplantation factors on outcome _J Clin Oncol_ 2001 19: 3340 3349 Article  CAS

  PubMed  Google Scholar  * Nagler A, Aker M, Or R _et al_. Low-intensity conditioning is sufficient to ensure engraftment in matched unrelated bone marrow transplantation _Exp Hematol_ 2001

29: 362 370 Article  CAS  PubMed  Google Scholar  * Russell LA, Jacobsen N, Heilmann C _et al_. Treatment of relapse after allogeneic BMT with donor leukocyte infusions in 16 patients _Bone

Marrow Transplant_ 1996 18: 411 414 CAS  PubMed  Google Scholar  * Bertz H, Burger JA, Kunzmann R _et al_. Adoptive immunotherapy for relapsed multiple myeloma after allogeneic bone marrow

transplantation (BMT): evidence for a graft-versus-myeloma effect _Leukemia_ 1997 11: 281 283 Article  CAS  PubMed  Google Scholar  * Dazzi F, Szydlo RM, Cross N _et al_. Durability of

responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia _Blood_ 2000 96: 2712 2716 CAS  PubMed  Google

Scholar  Download references ACKNOWLEDGEMENTS This work was supported in part by a special grant of the Ministry of Health (PHRC2000) and Amgen. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS

* Unité de Transplantation Médullaire, Centre Jean Perrin (CLCC), Clermont-Ferrand, France J-O Bay, J Fleury, B Choufi & J Dauplat * Service d'Hématologie, CHU Hôtel Dieu,

Clermont-Ferrand, France O Tournilhac * Unité de Radiodiagnostic, Centre Jean Perrin (CLCC), Clermont-Ferrand, France C Vincent & C Bailly * Unité de Transplantation et de Thérapie

Cellulaire, Institut Paoli Calmettes (CLCC), Marseille, France P Viens, C Faucher & D Blaise Authors * J-O Bay View author publications You can also search for this author inPubMed 

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THIS ARTICLE CITE THIS ARTICLE Bay, JO., Fleury, J., Choufi, B. _et al._ Allogeneic hematopoietic stem cell transplantation in ovarian carcinoma: results of five patients. _Bone Marrow

Transplant_ 30, 95–102 (2002). https://doi.org/10.1038/sj.bmt.1703609 Download citation * Received: 30 October 2001 * Accepted: 14 March 2002 * Published: 22 July 2002 * Issue Date: 01 July

2002 * DOI: https://doi.org/10.1038/sj.bmt.1703609 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link

is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * ovarian cancer * non-myeloablative regimen *

allogeneic transplantation * graft-versus-ovarian cancer