Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Société Française de Greffe de Moelle (SFGM)
Tanguy
Unité de Statistiques, Société de Greffe de Moelle, Paris
Search for more papers by this authorMilpied
Service d'Hématologie, Centre Hospitalier Hôtel-Dieu, Nantes
Search for more papers by this authorReiffers
Service d'Hématologie, Centre Hospitalier Haut Levêque, Pessac
Search for more papers by this authorCahn
Service d'Hématologie Adulte, Hôpital Jean Minjoz, Besancon
Search for more papers by this authorBlaise
Unité de Transplantation Médullaire, Institut Paoli Calmettes, Marseilles
Search for more papers by this authorDemeocq
Service d'Hématologie Pédiatrique, Centre Hospitalo-Universitaire Hôtel-Dieu, Clermont Ferrand
Search for more papers by this authorJouet
Service d'Hématologie, Centre Hospitalo-Universitaire Huriez, Lille
Search for more papers by this authorMichallet
Service d'Hématologie, Centre Hospitalo-Universitaire Huriez, Lille
Search for more papers by this authorIfrah
Service d'Hématologie, Centre Hospitalo-Universitaire, Angers
Search for more papers by this authorVilmer
Unité d'Hématologie-Immunologie, Hôpital Robert Debré, Paris
Search for more papers by this authorMolina
Service d'Hématologie, Centre Hospitalo-Universitaire Albert Michallon, Grenoble
Search for more papers by this authorLioure
Service d'Onco-Hématologie, Hôpital Hautepierre, Strasbourg
Search for more papers by this authorCavazzana-Calvo
Service d'Hématologie, Hôpital des Enfants Malades, Paris
Search for more papers by this authorPico
Service d'Hématologie Adulte, Institut Gustave Roussy, Villejuif
Search for more papers by this authorAttal
Service d'Hématologie, Centre Hospitalo-Universitaire Purpan, Toulouse
Search for more papers by this authorCuré
Service d'Onco-Hématologie, Centre Jean Perrin, Clermont Ferrand
Search for more papers by this authorBordigoni
Unité de Transplantation Médullaire, Hôpital de Brabois, Nancy
Search for more papers by this authorBuzyn-Veil
Service d'Hématologie, Hôpital Necker Adultes, Paris
Search for more papers by this authorLeporrier
Service d'Hématologie, Centre Hospitalo-Universitaire, Caen
Search for more papers by this authorFegueux
Service d'Hématologie, Centre Hospitalo-Universitaire, Montpellier
Search for more papers by this authorLutz
Service d'Onco-Hématologie, Hôpital Hautepierre, Strasbourg
Search for more papers by this authorVernant
Service d'Hématologie, Hôpital Pitié Salpêtrière, Paris
Search for more papers by this authorTanguy
Unité de Statistiques, Société de Greffe de Moelle, Paris
Search for more papers by this authorMilpied
Service d'Hématologie, Centre Hospitalier Hôtel-Dieu, Nantes
Search for more papers by this authorReiffers
Service d'Hématologie, Centre Hospitalier Haut Levêque, Pessac
Search for more papers by this authorCahn
Service d'Hématologie Adulte, Hôpital Jean Minjoz, Besancon
Search for more papers by this authorBlaise
Unité de Transplantation Médullaire, Institut Paoli Calmettes, Marseilles
Search for more papers by this authorDemeocq
Service d'Hématologie Pédiatrique, Centre Hospitalo-Universitaire Hôtel-Dieu, Clermont Ferrand
Search for more papers by this authorJouet
Service d'Hématologie, Centre Hospitalo-Universitaire Huriez, Lille
Search for more papers by this authorMichallet
Service d'Hématologie, Centre Hospitalo-Universitaire Huriez, Lille
Search for more papers by this authorIfrah
Service d'Hématologie, Centre Hospitalo-Universitaire, Angers
Search for more papers by this authorVilmer
Unité d'Hématologie-Immunologie, Hôpital Robert Debré, Paris
Search for more papers by this authorMolina
Service d'Hématologie, Centre Hospitalo-Universitaire Albert Michallon, Grenoble
Search for more papers by this authorLioure
Service d'Onco-Hématologie, Hôpital Hautepierre, Strasbourg
Search for more papers by this authorCavazzana-Calvo
Service d'Hématologie, Hôpital des Enfants Malades, Paris
Search for more papers by this authorPico
Service d'Hématologie Adulte, Institut Gustave Roussy, Villejuif
Search for more papers by this authorAttal
Service d'Hématologie, Centre Hospitalo-Universitaire Purpan, Toulouse
Search for more papers by this authorCuré
Service d'Onco-Hématologie, Centre Jean Perrin, Clermont Ferrand
Search for more papers by this authorBordigoni
Unité de Transplantation Médullaire, Hôpital de Brabois, Nancy
Search for more papers by this authorBuzyn-Veil
Service d'Hématologie, Hôpital Necker Adultes, Paris
Search for more papers by this authorLeporrier
Service d'Hématologie, Centre Hospitalo-Universitaire, Caen
Search for more papers by this authorFegueux
Service d'Hématologie, Centre Hospitalo-Universitaire, Montpellier
Search for more papers by this authorLutz
Service d'Onco-Hématologie, Hôpital Hautepierre, Strasbourg
Search for more papers by this authorVernant
Service d'Hématologie, Hôpital Pitié Salpêtrière, Paris
Search for more papers by this authorAbstract
Although recurrent malignancy is the most frequent indication for second stem cell transplantation (2nd SCT), there are few reports that include sufficiently large numbers of patients to enable prognostic factor analysis. This retrospective study includes 150 patients who underwent a 2nd SCT for relapsed acute myeloblastic leukaemia (n = 61), acute lymphoblastic leukaemia (n = 47) or chronic myeloid leukaemia (n = 42) after a first allogeneic transplant (including 26 T-cell-depleted). The median interval between the first transplant and relapse, and between relapse and second transplant was 17 months and 5 months respectively. After the 2nd SCT, engraftment occurred in 93% of cases, 32% of patients developed acute graft-vs.-host disease (GVHD) grade II and 38% chronic GVHD. The 5-year overall and disease-free survival were 32 ± 8% and 30 ± 8%, respectively, with a risk of relapse of 44 ± 12% and a transplant-related mortality of 45 ± 9%. In a multivariate analysis, five factors were associated with a better outcome after 2nd SCT: age < 16 years at second transplant; relapse occurring more than 12 months after the first transplant; transplantation from a female donor; absence of acute GVHD; and the occurrence of chronic GVHD. The best candidates for a second transplant are likely to be patients with acute leukaemia in remission before transplant, in whom the HLA-identical donor was female and who relapsed more than 1 year after the first transplant.
References
- 1 Arcese, W., Goldman, J.M., D'arcangelo, E., Schattenberg, A., Nardi, A., Apperley, J., Frassoni, F., Aversa, F., Prentice, H.G., Ljungman, P. (1993) Outcome for patients who relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia. Chronic Leukemia Working Party. European Bone Marrow Transplantation Group. Blood, 82, 3211 3219.
- 2 Atkinson, K., Biggs, J., Concannon, A., Dodds, A., Dale, B., Norman, J. (1986) Second marrow transplants for recurrence of haematological malignancy. Bone Marrow Transplantation, 1, 159 166.
- 3 Barrett, A.J., Locatelli, F., Treleaven, J.G., Gratwohl, A., Szydlo, R., Zwaan, F.E. (1991) Second transplants for leukaemic relapse after bone marrow transplantation: high early mortality but favourable effect of chronic GVHD on continued remission. A report by the EBMT Leukaemia Working Party. British Journal of Haematology, 79, 567 574.
- 4 Bonini, C., Verzeletti, S., Servida, P., Rossini, S., Traversari, C., Ferrari, G., Nobili, N., Mavilio, F., Bordignon, C. (1994) Transfer of the HSV-tk gene into donor peripheral blood lymphocytes for in vivo immunomodulation of donor anti-tumor immunity after allo BMT . Blood, 84, 110a.
- 5 Bosi, A., Bacci, S., Miniero, R., Locatelli, F., Laszlo, D., Longo, G., Busca, A., Van Lint, M.T., Di Bartolomeo, P., Amici, A.I. (1997) Second allogeneic bone marrow transplantation in acute leukemia: a multicenter study from the Gruppo Italiano Trapianto Di Midollo Osseo (GITMO). Leukemia, 11, 420 424.
- 6 Chiang, K.Y., Weisdorf, D.J., Davies, S.M., Enright, H., Kersey, J.H., McGlave, P.B., Miller, W., Ramsay, N.K., Steinbuch, M., Wagner, J.E., Blazar, B.R. (1996) Outcome of second bone marrow transplantation following a uniform conditioning regimen as therapy for malignant relapse. Bone Marrow Transplantation, 17, 39 42.
- 7
Cox, D.R. (1972) Regression models and life-tables.
Journal of the Royal Statistical Society, 34, 187 220.
10.1111/j.2517-6161.1972.tb00899.x Google Scholar
- 8 Cullis, J.O., Schwarer, A.P., Hughes, T.P., Hows, J.M., Franklin, I., Morgenstern, G., Goldman, J.M. (1992) Second transplants for patients with chronic myeloid leukaemia in relapse after original transplant with T-depleted donor marrow: feasibility of using busulphan alone for re-conditioning. British Journal of Haematology, 80, 33 39.
- 9 Drobyski, W.R., Keever, C.A., Roth, M.S., Koethe, S., Hanson, G., McFadden, P., Gottschall, J.R., Ash, R.C., Van Tuinen, P., Horowitz, M.M., Flomenberg, N. (1993) Salvage immunotherapy using donor leucocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose. Blood, 82, 2310 2318.
- 10 Elmaagacli, A.H., Beelen, D.W., Schaefer, U.W. (1997) A retrospective single centre study of the outcome of five different therapy approaches in 48 patients with relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation. Bone Marrow Transplantation, 20, 1045 1055.
- 11 Frassoni, F., Barrett, A.J., Granena, A., Ernst, P., Garhton, C., Kolb, H., Prentice, H.G., Vernant, J.P., Zwaan, F.E., Gratwohl, A. (1998) Relapse after allogeneic bone marrow transplantation for acute leukaemia: a survey by the EBMT of 117 cases. British Journal of Haematology, 70, 317 320.
- 12 Giralt, S., Escudier, S., Kantarjian, H., Deisseroth, A., Freireich, E.J., Anderson, B.S., O'brien, S., Andreeff, M., Fisher, H., Cork, A. (1993) Preliminary results of treatment with filgrastim for relapse of leukemia and myelodysplasia after allogeneic bone marrow transplantation. New England Journal of Medicine, 329, 757 761.
- 13 Giralt, S., Estey, E., Albitar, M., Van Besien, K., Rondon, G., Anderlini, P., O'brien, S., Khouri, I., Gajewski, J., Mehra, R., Claxton, D., Andersson, B., Beran, M., Przepiorka, D., Koller, C., Kornblau, S., Körbling, M., Keating, M., Kantarjian, H., Champlin, R. (1997) Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood, 89, 4531 4536.
- 14 Hansen, J.A., Jerald, P., Radich, J.P., Petterdorf, E., Martin, P.J., Anasetti, C. (1997) Retransplantation of marrow and hematopoietic stem cells from normal donors. In: Retransplantation (ed. by J.L. Touraine et al.), pp. 17 23. Kluwer Academic Publishers, The Netherlands.
- 15 Higano, C.S., Brixey, M., Bryant, E.M., Durnam, D.M., Doney, K., Sullivan, K.M., Singer, J.W. (1990) Durable complete remission of acute nonlymphocytic leukemia associated with discontinuation of immunosuppression following relapse after allogeneic bone marrow transplantation. A case report of a probable graft-versus-leukemia effect. Transplantation, 50, 175 177.
- 16 Higano, C.S., Raskind, W.H., Singer, J.W. (1992) Use of α interferon for the treatment of relapse of chronic myelogenous leukemia in chronic phase after allogeneic bone marrow transplantation. Blood, 80, 1437 1443.
- 17 Horowitz, M.M., Gale, R.P., Sondel, P.M., Goldman, J.M., Kersey, J., Kolb, H.J., Rimm, A.A., Ringden, O., Rozman, C., Speck, B., Truitt, R.L., Zwaan, E., Bortin, M.M. (1990) Graft-versus-leukemia reactions following bone marrow transplantation in humans. Blood, 75, 555 562.
- 18 Kaplan, E.L. & Meier, P. (1958) Non-parametric estimation from incomplete observations. Journal of the American Statistical Association, 53, 457 481.
- 19 Kishi, K., Takahashi, S., Gondo, H., Shiobara, S., Kanamaru, A., Kato, S., Hirabayashi, N., Moriyama, Y., Harada, M., Asano, S., Hara, H., Shibata, A. (1997) Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes. Bone Marrow Transplantation, 19, 461 466.
- 20 Kolb, H.J., Mittermuller, J., Clemm, C., Holler, E., Ledderose, G., Brehm, G., Heim, M., Wilmanns, W. (1990) Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood, 76, 2462 2465.
- 21 Kumar, L. (1994) Leukemia: management of relapse after allogeneic bone marrow transplantation. Journal of Clinical Oncology, 12, 1710 1717.
- 22 Mehta, J., Powles, R., Treleaven, J., Horton, C., Meller, S., Pinkerton, C.R., Singhal, S. (1997) Outcome of acute leukemia relapsing after bone marrow transplantation: utility of second transplants and adoptive immunotherapy. Bone Marrow Transplantation, 19, 709 719.
- 23 Mrsic, M., Horowitz, M.M., Atkinson, K., Biggs, J.C., Champlin, R.E., Ehninger, G., Gajewski, J.L., Gale, R.P., Herzig, R.H., Prentice, H.G. (1992) Second HLA-identical sibling transplants for leukemia recurrence. Bone Marrow Transplantation, 9, 269 275.
- 24 Offit, K., Burns, J.P., Cunningham, I., Jhanwar, S.C., Black, P., Kernan, N.A., O'reilly, R.J., Chaganti, R.S. (1990) Cytogenetic analysis of chimerism and leukemia relapse in chronic myelogenous leukemia patients after T-cell depleted bone marrow transplantation. Blood, 75, 1346 1355.
- 25 Peto, R., Pike, M.C., Armitage, P. (1977) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. Part II. Analysis and examples. British Journal of Cancer, 35, 1 39.
- 26 Radich, J.P., Sanders, J.E., Buckner, C.D., Martin, P.J., Petersen, F.B., Bensinger, W., McDonald, G.B., Mori, M., Schoch, G., Hansen, J.A. (1993) Second allogeneic marrow transplantation for patients with recurrent leukemia after initial transplant with total-body irradiation-containing regimens. Journal of Clinical Oncology, 11, 304 313.
- 27 Russel, J.A., Bowen, T., Brown, C., Luider, J., Ruether, J.D., Stewart, D., Jorgenson, K., Coppes, M.J., Turner, A.R., Larratt, L., Chaudhry, A., Booth, K., Poon, M.C., Klassen, J. (1996) Second allogeneic transplants for leukemia using blood instead of bone marrow as a source of hematopoietic cells. Bone Marrow Transplantation, 18, 501 505.
- 28 Slavin, S., Naparstek, E., Nagler, A., Ackertein, A., Karpelushnik, J., Or, R. (1995) Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes. Experimental Hematology, 23, 1553 1562.
- 29 Thomas, E.D., Storb, R., Clift, R.A., Fefer, A., Johnson, L., Neiman, P.E., Lerner, K.G., Glucksberg, H., Buckner, C.D. (1975) Bone marrow transplantation. New England Journal of Medicine, 292, 832 843.
- 30 Weiden, P., Flournoy, N., Thomas, E.D., Prentice, R., Fefer, A., Buckner, D., Storb, R. (1979) Antileukemic effect of graft-versus-host disease in human recipients of allogeneic marrow grafts. New England Journal of Medicine, 300, 1068 1073.