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Published in: Annals of Hematology 5/2005

01-05-2005 | Original Article

Reduced-intensity conditioning followed by allografting of CD34-selected stem cells and ≤106/kg T cells may have an adverse effect on transplant-related mortality

Authors: Udo F. Hartwig, Nils Winkelmann, Thomas Wehler, Sebastian Kreiter, Peter M. Schneider, Ralf G. Meyer, Andrew J. Ullmann, Christoph Huber, Karin Kolbe, Wolfgang Herr

Published in: Annals of Hematology | Issue 5/2005

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Abstract

In patients undergoing allogeneic peripheral blood stem cell (PBSC) transplantation after reduced-intensity conditioning (RIC), graft-versus-host disease (GVHD) represents a major cause of morbidity and mortality. T-cell depletion (TCD) prevents GVHD but carries potential risks of graft failure, opportunistic infections, and disease relapse. We explored ex vivo TCD of stem cell allografts that were administered after RIC treatment. Thirteen high-risk patients with hematological malignancies were treated with a fludarabine/melphalan-based RIC regimen followed by transplantation of immunomagnetically selected CD34+ PBSC from HLA-identical sibling or matched unrelated donors. Patients were sequentially enrolled in two cohorts: group A (n=6) received antithymocyte globulin (ATG) during conditioning and 105 donor T cells/kg at transplantation, while group B (n=7) received 106 donor T cells/kg without ATG pretreatment. Primary graft failure occurred in two patients of group A and in one patient of group B. Complete donor chimerism persisting more than 1 year was achieved in two cases per cohort. Acute grade II to IV or chronic extensive GVHD were observed in a total of six patients (group A, 2; group B, 4). Procedure-related deaths were mainly due to severe pneumonia occurring in two patients of group A and in five patients of group B. These results suggest that CD34 selection of reduced-intensity PBSC allografts may cause adverse effects upon specific antimicrobial immunity which can lead to fatal infections, particularly in high-risk patients. In our study, simultaneous add-back of ≤106/kg donor T cells was unable to compensate for this deficiency.
Literature
1.
go back to reference Alyea EP, Soiffer RJ, Canning C, Neuberg D, Schlossman R, Pickett C, Collins H, Wang Y, Anderson KC, Ritz J (1998) Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant. Blood 91:3671–3680PubMed Alyea EP, Soiffer RJ, Canning C, Neuberg D, Schlossman R, Pickett C, Collins H, Wang Y, Anderson KC, Ritz J (1998) Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant. Blood 91:3671–3680PubMed
2.
go back to reference Bacigalupo A (2000) Second EBMT workshop on reduced intensity allogeneic hemopoietic stem cell transplants (RI-HSCT). Bone Marrow Transplant 29:191–195 Bacigalupo A (2000) Second EBMT workshop on reduced intensity allogeneic hemopoietic stem cell transplants (RI-HSCT). Bone Marrow Transplant 29:191–195
3.
go back to reference Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Barbanti M, Sacchi N, Van Lint MT, Bosi A (2001) Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midoll Osseo (GITMO). Blood 98:2942–2947 Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Barbanti M, Sacchi N, Van Lint MT, Bosi A (2001) Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midoll Osseo (GITMO). Blood 98:2942–2947
4.
go back to reference Baron F, Siquet J, Schaaf-Lafontaine N, Baudoux E, Hermanne JP, Fillet G, Beguin Y (2002) Pre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation. Haematologica 87:78–88 Baron F, Siquet J, Schaaf-Lafontaine N, Baudoux E, Hermanne JP, Fillet G, Beguin Y (2002) Pre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation. Haematologica 87:78–88
5.
go back to reference Bunn D, Lea CK, Bevan DJ, Higgins RM, Hendry BM (1996) The pharmacokinetics of anti-thymocyte globulin (ATG) following intravenous infusion in man. Clin Nephrol 45:29–32 Bunn D, Lea CK, Bevan DJ, Higgins RM, Hendry BM (1996) The pharmacokinetics of anti-thymocyte globulin (ATG) following intravenous infusion in man. Clin Nephrol 45:29–32
6.
go back to reference Carella AM, Lerma E, Dejana A, Corsetti MT, Celesti L, Bruni R, Benvenuto F, Figari O, Parodi C, Carlier P, Florio G, Lercari G, Valbonesi M, Casarino L, De Stefano F, Geniram A, Venturino M, Tedeschi L, Palmieri G, Piaggio G, Podesta M, Frassoni F, Van Lint MT, Marmont AM, Bacigalupo A (1998) Engraftment of HLA-matched sibling hematopoietic stem cells after immunosuppressive conditioning regimen in patients with hematologic neoplasias. Haematologica 83:904–909 Carella AM, Lerma E, Dejana A, Corsetti MT, Celesti L, Bruni R, Benvenuto F, Figari O, Parodi C, Carlier P, Florio G, Lercari G, Valbonesi M, Casarino L, De Stefano F, Geniram A, Venturino M, Tedeschi L, Palmieri G, Piaggio G, Podesta M, Frassoni F, Van Lint MT, Marmont AM, Bacigalupo A (1998) Engraftment of HLA-matched sibling hematopoietic stem cells after immunosuppressive conditioning regimen in patients with hematologic neoplasias. Haematologica 83:904–909
7.
go back to reference Charkrabarti S, Mackinnon S, Chopra R, Kottaridis PD, Peggs K, O’Gorman P, Chakraverty R, Marshall T, Osman H, Mahendra P, Craddock C, Waldmann H, Hale G, Fegan CD, Yong K, Goldstone AH, Linch DC, Milligan DW (2002) High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood 99:4357–4363 Charkrabarti S, Mackinnon S, Chopra R, Kottaridis PD, Peggs K, O’Gorman P, Chakraverty R, Marshall T, Osman H, Mahendra P, Craddock C, Waldmann H, Hale G, Fegan CD, Yong K, Goldstone AH, Linch DC, Milligan DW (2002) High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood 99:4357–4363
8.
go back to reference Chakraverty R, Peggs K, Chopra R, Milligan DW, Kottaridis PD, Verfuerth S, Geary J, Thuraisundaram D, Branson K, Chakrabarti S, Mahendra P, Craddock C, Parker A, Hunter A, Hale G, Waldmann H, Williams CD, Yong K, Linch DC, Goldstone AH, Mackinnon S (2002) Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood 99:1071–1078 Chakraverty R, Peggs K, Chopra R, Milligan DW, Kottaridis PD, Verfuerth S, Geary J, Thuraisundaram D, Branson K, Chakrabarti S, Mahendra P, Craddock C, Parker A, Hunter A, Hale G, Waldmann H, Williams CD, Yong K, Linch DC, Goldstone AH, Mackinnon S (2002) Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood 99:1071–1078
9.
go back to reference Childs R, Clave E, Contentin N, Javasekra D, Hensel N, Leitman S, Read EJ, Carter C, Bahceci E, Young NS, Barrett AJ (1999) Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. Blood 94:3234–3241PubMed Childs R, Clave E, Contentin N, Javasekra D, Hensel N, Leitman S, Read EJ, Carter C, Bahceci E, Young NS, Barrett AJ (1999) Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. Blood 94:3234–3241PubMed
10.
go back to reference Couriel D, Canosa J, Engler H, Collins A, Dunbar C, Barett AJ (1996) Early reactivation of cytomegalovirus and high risk of interstitial pneumonitis following T-depleted BMT for adults with hematological malignancies. Bone Marrow Transplant 18:347–353 Couriel D, Canosa J, Engler H, Collins A, Dunbar C, Barett AJ (1996) Early reactivation of cytomegalovirus and high risk of interstitial pneumonitis following T-depleted BMT for adults with hematological malignancies. Bone Marrow Transplant 18:347–353
11.
go back to reference Craddock C, Bardy P, Kreiter S, Johnston R, Apperley J, Marks D, Huber C, Kolbe K, Goulding R, Lawler M, Goldman J, Hughes T, Derigs G (2000) Engraftment of T-cell-depleted allogeneic haematopoietic stem cells using a reduced intensity conditioning regimen. Br J Haematol 111:797–800 Craddock C, Bardy P, Kreiter S, Johnston R, Apperley J, Marks D, Huber C, Kolbe K, Goulding R, Lawler M, Goldman J, Hughes T, Derigs G (2000) Engraftment of T-cell-depleted allogeneic haematopoietic stem cells using a reduced intensity conditioning regimen. Br J Haematol 111:797–800
12.
go back to reference Dazzi F, Szydlo RM, Goldman JM (1999) Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplant: where we now stand. Exp Hematol 10:1477–1486 Dazzi F, Szydlo RM, Goldman JM (1999) Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplant: where we now stand. Exp Hematol 10:1477–1486
13.
go back to reference Fagioli F, Ricchiardi A, Carnevale-Schianca F (2002) Non-myeloablative allogeneic hematopoietic stem cell transplants. Haematologica 87 [8 Suppl]:13–19 Fagioli F, Ricchiardi A, Carnevale-Schianca F (2002) Non-myeloablative allogeneic hematopoietic stem cell transplants. Haematologica 87 [8 Suppl]:13–19
14.
go back to reference Ferrera JLM, Antin JH (1999) Pathophysiology of graft-versus-host disease. In: Thomas ED, Blume KG, Forman SJ (eds) Hematopoietic stem cell transplantation. Blackwell Scientific Publications, Boston, MA, pp 305–315 Ferrera JLM, Antin JH (1999) Pathophysiology of graft-versus-host disease. In: Thomas ED, Blume KG, Forman SJ (eds) Hematopoietic stem cell transplantation. Blackwell Scientific Publications, Boston, MA, pp 305–315
15.
go back to reference Giralt S, Hester J, Huh Y, Hirsch-Ginsberg C, Rondon G, Seong D, Lee M, Gajewski J, Van Besien K, Khouri I (1995) CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. Blood 86:4337–4343 Giralt S, Hester J, Huh Y, Hirsch-Ginsberg C, Rondon G, Seong D, Lee M, Gajewski J, Van Besien K, Khouri I (1995) CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. Blood 86:4337–4343
16.
go back to reference 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, Korbling M, Keating M, Kantarjian H, Champlin R (1997) Engraftment of allogeneic hematopoietic progenitor cells with purine analogue-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 89:4531–4536PubMed 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, Korbling M, Keating M, Kantarjian H, Champlin R (1997) Engraftment of allogeneic hematopoietic progenitor cells with purine analogue-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 89:4531–4536PubMed
17.
go back to reference Goerner M, Kordelas L, Thalheimer M, Luft T, Pfeiffer S, Ustaoglu F, Punzel M, Weber-Nordt R, Moos M, Goldschmidt H, Ho AD (2002) Stable mixed chimerism after T cell-depleted allogeneic hematopoietic stem cell transplantation using conditioning with low-dose total body irradiation and fludarabine. Bone Marrow Transplant 29:621–624 Goerner M, Kordelas L, Thalheimer M, Luft T, Pfeiffer S, Ustaoglu F, Punzel M, Weber-Nordt R, Moos M, Goldschmidt H, Ho AD (2002) Stable mixed chimerism after T cell-depleted allogeneic hematopoietic stem cell transplantation using conditioning with low-dose total body irradiation and fludarabine. Bone Marrow Transplant 29:621–624
18.
go back to reference Goldman JM, Gale RP, Horowitz MM, Biggs JC, Champlin RE, Gluckman E, Hoffmann RG, Jacobsen SJ, Marmont AM, McGlave PB (1988) Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: increased risk of relapse associated with T-cell depletion. Ann Intern Med 108:806–814PubMed Goldman JM, Gale RP, Horowitz MM, Biggs JC, Champlin RE, Gluckman E, Hoffmann RG, Jacobsen SJ, Marmont AM, McGlave PB (1988) Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: increased risk of relapse associated with T-cell depletion. Ann Intern Med 108:806–814PubMed
19.
go back to reference Ho VT, Soiffer RJ (2001) The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation. Blood 98:3192–3204 Ho VT, Soiffer RJ (2001) The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation. Blood 98:3192–3204
20.
go back to reference Ho AYL, Kenyon M, El-Hemaidi I, Devereux S, Pagliuca A, Mufti GJ (2003) Reduced-intensity allogeneic hematopoietic stem cell transplantation with alemtuzumab conditioning regimens: survival does not plateau until after day 200. Blood 101:779–780 Ho AYL, Kenyon M, El-Hemaidi I, Devereux S, Pagliuca A, Mufti GJ (2003) Reduced-intensity allogeneic hematopoietic stem cell transplantation with alemtuzumab conditioning regimens: survival does not plateau until after day 200. Blood 101:779–780
21.
go back to reference Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, Rimm AA, Ringden O, Rozman C, Speck B (1990) Graft-versus-leukemia reactions after bone marrow transplantation. Blood 75:555–562PubMed Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, Rimm AA, Ringden O, Rozman C, Speck B (1990) Graft-versus-leukemia reactions after bone marrow transplantation. Blood 75:555–562PubMed
22.
go back to reference Horwitz ME, Barrett AJ, Brown MR, Carter CS, Childs R, Gallin JI, Holland SM, Linton GF, Miller JA, Leitman SF, Read EJ, Malech HL (2001) Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft. N Engl J Med 344:881–888 Horwitz ME, Barrett AJ, Brown MR, Carter CS, Childs R, Gallin JI, Holland SM, Linton GF, Miller JA, Leitman SF, Read EJ, Malech HL (2001) Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft. N Engl J Med 344:881–888
23.
go back to reference Khouri IF, Keating M, Körbling M, Przepiorka D, Anderlini P, O’Brien S, Giralt S, Ippoliti C, von Wolff B, Gajewski J, Donato M, Claxton D, Ueno N, Andersson B, Gee A, Champlin R (1998) Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonmyeloablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment of lymphoid malignancies. J Clin Oncol 18:2817–2824 Khouri IF, Keating M, Körbling M, Przepiorka D, Anderlini P, O’Brien S, Giralt S, Ippoliti C, von Wolff B, Gajewski J, Donato M, Claxton D, Ueno N, Andersson B, Gee A, Champlin R (1998) Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonmyeloablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment of lymphoid malignancies. J Clin Oncol 18:2817–2824
24.
go back to reference Kolb HJ, Mittermüller 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 76:2462–2465PubMed Kolb HJ, Mittermüller 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 76:2462–2465PubMed
25.
go back to reference Kottaridis PD, Milligan DW, Chopra R, Chakraverty RK, Chakrabarti S, Robinson S, Peggs K, Verfuerth S, Pettengell R, Marsh JC, Schey S, Mahendra P, Morgan GJ, Hale G, Waldmann H, de Elvira MC, Williams CD, Devereux S, Linch DC, Goldstone AH, Mackinnon S (2000) In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 96:2419–2425 Kottaridis PD, Milligan DW, Chopra R, Chakraverty RK, Chakrabarti S, Robinson S, Peggs K, Verfuerth S, Pettengell R, Marsh JC, Schey S, Mahendra P, Morgan GJ, Hale G, Waldmann H, de Elvira MC, Williams CD, Devereux S, Linch DC, Goldstone AH, Mackinnon S (2000) In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 96:2419–2425
26.
go back to reference Kreiter S, Winkelmann N, Schneider PM, Schuler M, Fischer T, Ullmann AJ, Huber C, Derigs HG, Kolbe K (2001) Failure of sustained engraftment after non-myeloablative conditioning with low-dose TBI and T cell-reduced allogeneic peripheral stem cell transplantation. Bone Marrow Transplant 28:157–161 Kreiter S, Winkelmann N, Schneider PM, Schuler M, Fischer T, Ullmann AJ, Huber C, Derigs HG, Kolbe K (2001) Failure of sustained engraftment after non-myeloablative conditioning with low-dose TBI and T cell-reduced allogeneic peripheral stem cell transplantation. Bone Marrow Transplant 28:157–161
27.
go back to reference Ljungman P, Brand R, Einsele H, Frassoni F, Niederwieser D, Cordonnier C (2003) Donor CMV serologic status and outcome of CMV-seropositive recipients after unrelated donor stem cell transplantation: an EBMT megafile analysis. Blood 102:4255–4260 Ljungman P, Brand R, Einsele H, Frassoni F, Niederwieser D, Cordonnier C (2003) Donor CMV serologic status and outcome of CMV-seropositive recipients after unrelated donor stem cell transplantation: an EBMT megafile analysis. Blood 102:4255–4260
28.
go back to reference Maraninchi D, Gluckman E, Blaise D, Guyotat D, Rio B, Pico JL, Leblond V, Michallet M, Dreyfus F, Ifrah N (1987) Impact of T-cell depletion on outcome of allogeneic bone-marrow transplantation for standard-risk leukaemias. Lancet 2:175–178CrossRefPubMed Maraninchi D, Gluckman E, Blaise D, Guyotat D, Rio B, Pico JL, Leblond V, Michallet M, Dreyfus F, Ifrah N (1987) Impact of T-cell depletion on outcome of allogeneic bone-marrow transplantation for standard-risk leukaemias. Lancet 2:175–178CrossRefPubMed
29.
go back to reference Martin PJ, Hansen JA, Buckner CD, Sanders JE, Deeg HJ, Stewart P, Appelbaum FR, Clift R, Fefer A, Witherspoon RP (1985) Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts. Blood 3:664–672 Martin PJ, Hansen JA, Buckner CD, Sanders JE, Deeg HJ, Stewart P, Appelbaum FR, Clift R, Fefer A, Witherspoon RP (1985) Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts. Blood 3:664–672
30.
go back to reference McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG, Chauncey TR, Gooley TA, Hegenbart U, Nash RA, Radich J, Wagner JL, Minor S, Appelbaum FR, Bensinger WI, Bryant E, Flowers ME, Georges GE, Grumet FC, Kiem HP, Torok-Storb B, Yu C, Blume KG, Storb RF (2001) Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 97:3390–3400CrossRefPubMed McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG, Chauncey TR, Gooley TA, Hegenbart U, Nash RA, Radich J, Wagner JL, Minor S, Appelbaum FR, Bensinger WI, Bryant E, Flowers ME, Georges GE, Grumet FC, Kiem HP, Torok-Storb B, Yu C, Blume KG, Storb RF (2001) Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 97:3390–3400CrossRefPubMed
31.
go back to reference Nash RA, Storb R (1996) Graft-versus-host effect after allogeneic hematopoietic stem cell transplantation: GVHD and GVL. Curr Opin Immunol 8:674–680 Nash RA, Storb R (1996) Graft-versus-host effect after allogeneic hematopoietic stem cell transplantation: GVHD and GVL. Curr Opin Immunol 8:674–680
32.
go back to reference Niederwieser D, Maris M, Shizuru JA, Petersdorf E, Hegenbart U, Sandmaier BM, Maloney DG, Storer B, Lange T, Chauncey T, Deininger M, Ponisch W, Anasetti C, Woolfrey A, Little MT, Blume KG, McSweeney PA, Storb RF (2003) Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with haematological diseases. Blood 101:1620–1629CrossRefPubMed Niederwieser D, Maris M, Shizuru JA, Petersdorf E, Hegenbart U, Sandmaier BM, Maloney DG, Storer B, Lange T, Chauncey T, Deininger M, Ponisch W, Anasetti C, Woolfrey A, Little MT, Blume KG, McSweeney PA, Storb RF (2003) Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with haematological diseases. Blood 101:1620–1629CrossRefPubMed
33.
go back to reference Passweg JR, Meyer-Monard S, Gregor M, Favre G, Heim D, Ebnoether M, Tichelli A, Gratwohl A (2002) High stem cell dose will not compensate for T cell depletion in allogeneic non-myeloablative stem cell transplantation. Bone Marrow Transplant 30:267–271 Passweg JR, Meyer-Monard S, Gregor M, Favre G, Heim D, Ebnoether M, Tichelli A, Gratwohl A (2002) High stem cell dose will not compensate for T cell depletion in allogeneic non-myeloablative stem cell transplantation. Bone Marrow Transplant 30:267–271
34.
go back to reference Popplewell LL, Forman SJ (2002) Is there an upper age limit for bone marrow transplantation? Bone Marrow Transplant 29:277–284 Popplewell LL, Forman SJ (2002) Is there an upper age limit for bone marrow transplantation? Bone Marrow Transplant 29:277–284
35.
go back to reference Prentice HG, Blacklock HA, Janossy G, Gilmore MJ, Price-Jones L, Tidman N, Trejdosiewicz LK, Skeggs DB, Panjwani D, Ball S (1984) Depletion of T lymphocytes in donor marrow prevents significant graft-versus-host disease in matched allogeneic leukaemic marrow transplant recipients. Lancet 3:472–476 Prentice HG, Blacklock HA, Janossy G, Gilmore MJ, Price-Jones L, Tidman N, Trejdosiewicz LK, Skeggs DB, Panjwani D, Ball S (1984) Depletion of T lymphocytes in donor marrow prevents significant graft-versus-host disease in matched allogeneic leukaemic marrow transplant recipients. Lancet 3:472–476
36.
go back to reference Schetelig J, Kröger N, Held TK, Thiede C, Krusch A, Zabelina T, Dubiel M, Rick O, Bornhauser M, Ehninger G, Zander AR, Siegert W (2002) Allogeneic transplantation after reduced conditioning in high risk patients is complicated by a high incidence of acute and chronic graft-versus-host disease. Haematologica 87:299–305 Schetelig J, Kröger N, Held TK, Thiede C, Krusch A, Zabelina T, Dubiel M, Rick O, Bornhauser M, Ehninger G, Zander AR, Siegert W (2002) Allogeneic transplantation after reduced conditioning in high risk patients is complicated by a high incidence of acute and chronic graft-versus-host disease. Haematologica 87:299–305
37.
go back to reference Schneider PM, Kreiter S et al (2003) Quantification of fluorescent STR genotyping results for chimerism control after bone marrow transplantation. In: Brinkmann B, Carracedo A (eds) Prog. Forensic Genetics, 9 Int. Congress Series 1239. Elsevier, Amsterdam, pp 653–656 Schneider PM, Kreiter S et al (2003) Quantification of fluorescent STR genotyping results for chimerism control after bone marrow transplantation. In: Brinkmann B, Carracedo A (eds) Prog. Forensic Genetics, 9 Int. Congress Series 1239. Elsevier, Amsterdam, pp 653–656
38.
go back to reference Slavin S, Naparstek E, Nagler A, Ackerstein A, Kapelushnik Y, Or R (1995) Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes. Exp Hematol 14:1553–1562 Slavin S, Naparstek E, Nagler A, Ackerstein A, Kapelushnik Y, Or R (1995) Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes. Exp Hematol 14:1553–1562
39.
go back to reference Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R (1998) Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and non-malignant hematologic disease. Blood 91:756–763PubMed Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R (1998) Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and non-malignant hematologic disease. Blood 91:756–763PubMed
40.
go back to reference Storb R, Yu C, Wagner JL, Deeg HJ, Nash RA, Kiem HP, McSweeney P, Leisenring W, Schulman H (1997) Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 89:3048–3054PubMed Storb R, Yu C, Wagner JL, Deeg HJ, Nash RA, Kiem HP, McSweeney P, Leisenring W, Schulman H (1997) Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 89:3048–3054PubMed
41.
go back to reference Sykes M, Preffer F, McAfee S, Seidman SL, Weymouth D, Andrews DM, Colby C, Sackstein R, Sachs DH, Spitzer TR (1999) Mixed lymphohaemopoietic chimerism and graft-versus-lymphoma effects after non-myeloablative therapy and HLA-mismatched bone marrow transplantation. Lancet 353:1755–1759CrossRefPubMed Sykes M, Preffer F, McAfee S, Seidman SL, Weymouth D, Andrews DM, Colby C, Sackstein R, Sachs DH, Spitzer TR (1999) Mixed lymphohaemopoietic chimerism and graft-versus-lymphoma effects after non-myeloablative therapy and HLA-mismatched bone marrow transplantation. Lancet 353:1755–1759CrossRefPubMed
42.
go back to reference Thomas ED, Storb R, Clift RA, Fefer A, Johnson L, Neiman PE, Lerner KG, Glucksberg H, Buckner CD (1975) Bone marrow transplantation. N Engl J Med 292:895–902PubMed Thomas ED, Storb R, Clift RA, Fefer A, Johnson L, Neiman PE, Lerner KG, Glucksberg H, Buckner CD (1975) Bone marrow transplantation. N Engl J Med 292:895–902PubMed
43.
go back to reference Tiberghien P, Ferrand C, Lioure B, Milpied N, Angonin R, Deconinck E, Certoux JM, Robinet E, Saas P, Petracca B, Juttner C, Reynolds CW, Longo DL, Herve P, Cahn JY (2001) Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft. Blood 97:63–72 Tiberghien P, Ferrand C, Lioure B, Milpied N, Angonin R, Deconinck E, Certoux JM, Robinet E, Saas P, Petracca B, Juttner C, Reynolds CW, Longo DL, Herve P, Cahn JY (2001) Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft. Blood 97:63–72
44.
go back to reference Urbano-Ispizua A, Rozman C, Pimentel P, Solano C, de la Rubia J, Brunet S, Perez-Oteiza J, Ferra C, Zuazu J, Caballero D, Carvalhais A, Diez JL, Espigado I, Martinez C, Campilho F, Sanz MA, Sierra J, Garcia-Conde J, Montserrat E, Spanish Group for Allogenic Peripheral Blood Transplantation (2001) The number of CD3+ cells is the most important factor for graft failure after allogeneic transplantation of CD34+ selected cells from peripheral blood from HLA-identical siblings. Blood 97:383–387 Urbano-Ispizua A, Rozman C, Pimentel P, Solano C, de la Rubia J, Brunet S, Perez-Oteiza J, Ferra C, Zuazu J, Caballero D, Carvalhais A, Diez JL, Espigado I, Martinez C, Campilho F, Sanz MA, Sierra J, Garcia-Conde J, Montserrat E, Spanish Group for Allogenic Peripheral Blood Transplantation (2001) The number of CD3+ cells is the most important factor for graft failure after allogeneic transplantation of CD34+ selected cells from peripheral blood from HLA-identical siblings. Blood 97:383–387
45.
go back to reference Urbano-Ispizua A, Rozman C, Pimentel P, Solano C, de la Rubia J, Brunet S, Perez-Oteyza J, Ferra C, Zuazu J, Caballero D, Bargay J, Carvalhais A, Diez JL, Espigado I, Alegre A, Rovira M, Campilho F, Odriozola J, Sanz MA, Sierra J, Garcia-Conde J, Montserrat E, Spanish Group for Allogeneic Peripheral Blood Transplantation (Grupo Espanol de Trasplante Hemopoyetico) and Instituto Portugues de Oncologia-Porto (2002) Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings. Blood 100:724–727 Urbano-Ispizua A, Rozman C, Pimentel P, Solano C, de la Rubia J, Brunet S, Perez-Oteyza J, Ferra C, Zuazu J, Caballero D, Bargay J, Carvalhais A, Diez JL, Espigado I, Alegre A, Rovira M, Campilho F, Odriozola J, Sanz MA, Sierra J, Garcia-Conde J, Montserrat E, Spanish Group for Allogeneic Peripheral Blood Transplantation (Grupo Espanol de Trasplante Hemopoyetico) and Instituto Portugues de Oncologia-Porto (2002) Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings. Blood 100:724–727
46.
go back to reference Weiden PL, Flournoy N, Thomas ED, Prentice R, Fefer A, Buckner CD, Storb R (1979) Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med 300:1068–1073PubMed Weiden PL, Flournoy N, Thomas ED, Prentice R, Fefer A, Buckner CD, Storb R (1979) Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med 300:1068–1073PubMed
Metadata
Title
Reduced-intensity conditioning followed by allografting of CD34-selected stem cells and ≤106/kg T cells may have an adverse effect on transplant-related mortality
Authors
Udo F. Hartwig
Nils Winkelmann
Thomas Wehler
Sebastian Kreiter
Peter M. Schneider
Ralf G. Meyer
Andrew J. Ullmann
Christoph Huber
Karin Kolbe
Wolfgang Herr
Publication date
01-05-2005
Publisher
Springer-Verlag
Published in
Annals of Hematology / Issue 5/2005
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-004-1001-5

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