Abstract
NST is becoming a widely accepted method for allogeneic HSCT. Much experience has been gained, and the biology, indications and limitations are becoming clearer. N onmyeloablative conditioning allows consistent engraftment of allografts from matched related, unrelated, and even partially matched donors. NST has been able to reduce the toxicity of allogeneic HSCT. The better immediate outcome produces better overall DFS. NST was feasible in elderly patients with almost no upper age limit56, and in patients with organ dysfunction or other comorbidities precluding standard ablative conditioning. NST has also reduced the regimen-related toxicity of allogeneic HSCT in high-risk setting such as HSCT in heavily pretreated patients or following failure of a prior transplant procedure and in the unrelated setting. 49,51 NST is rapidly becoming the treatment of choice in these indications where toxicity of standard ablative therapy is unacceptable. In certain malignancies such as in NHL, Hodgkin’s disease and mUltiple myeloma, standard ablative NST has been reported to result in exceptionally high treatment related mortality, and NST is being investigated as a more reasonable alternative. NST may reduce the toxicity of the procedure even in younger patients who are eligible for ablative HSCT as well, however the long-term impact on patient outcome in this group is not yet established, and NST merits further investigation in prospective comparative trials. As described above, the known susceptibility of the underlying malignancy to GVT, the response to prior chemotherapy and bulk of residual disease, and the type of donor are other factors to consider when considering NST, and when selecting a regimen. The optimal preparative regimen needs to be defined. Ultimately less chemotherapy will be used and more specific immune-modulation, rather than intense nonspecific immunosuppression, will be used to achieve HVG tolerance. Preliminary animal models using costimulation blockade for specific induction of tolerance are promising steps towards achievement of this goa1.36
Although much progress has been achieved with consistent achievement of engraftment with NST, GVHD and disease recurrence remain major obstacles to successful treatment. Existing clinical data suggest that NST does limit the incidence and severity of GVHD. Limitation of regimen-related toxicity, and bilateral transplantation tolerance afforded by mixed chimerism, are believed to have a major role in limiting GVHD. However GVHD remains the primary cause of treatment-related mortality. The development of techniques to separate GVHD and GVL are essential for further improvement of NST outcome. Better understanding of the biology and targets of GVHD and GVL may allow the elimination of alloreactive T -cells responsible for GVHD from the graft while retaining T -cells with GVL and infection control potential. Recurrence of the underlying malignancy is a major complication when NST is attempted in patients with chemo-refractory diseases and with high tumor bulk. Reduced toxicity regimens such as the FBI ATG regimen have been somewhat more successful in controlling disease progression until a potent GVT effect is established. However novel approaches are urgently required. NST serves as a platform for cellular immunotherapy. Judicious use of pre-emptive DLI needs to be explored. DLI may be amplified by activation of donor lymphocytes with IL-2 or in vivo administration of IL_2. 42 Identification of tumor antigens will lead the way to ex-vivo generation and expansion of tumor specific cytotoxic T-lymphocytes to be used as potent immunotherapy without the hazards of GVHD.
Allogeneic transplantation is rapidly changing from administration of supra-lethal doses of chemotherapy and radiation, trying to physically eliminate the ‘last tumor cell’, to the more subtle and tolerated sophisticated immunotherapy. This effort will focus on specific induction of HVG tolerance followed by induction of tumor-specific GVT effect to cure the underlying malignancy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Thomas ED, Storb R, Clift RA, Fefer A, Johnson L, Nieman PE, Lender KG, Glucksberg H, Buckner CD. Bone marrow transplantation.N Engl JMed1975;292:832–843.
Armitage JO. Bone marrow transplantation.N Engl J Med1994;330:827–838.
Slavin S. New strategies for bone marrow transplantation.Curr Opin Immunol2000;12:542–551.
Champlin R, Khouri, Shimoni A, Gajewski J, Kornblau S, Molldrem J, Ueno N, Giralt S, Anderlini P. Harnessing graft-versus-malignancy: nonmyeloablative preparative regimens for allogeneic haematopoietic transplantation. An evolving strategy for adoptive immunotherapy.Br J Haematol2000; 11: 18–29.
Gale RP, Champlin RE. How does bone marrow transplantation cure leukemia?Lancet1984; 2:28–30.
Slavin S, Weiss L, Morecki S, Weigensberg M. Eradication of murine leukemia with histocompatible marrow grafts in mice conditioned with total lymphoid irradiation (TLI).Cancer Immunol Immunother1981;11:155–161.
Bortin MM, Rimm AA, Saltzxtein EC. Graft versus leukemia: Quantification of adoptive immunotherapy in murine leukemia.Science1973;179: 811–813.
Truiit R, LeFever A, Shih CY. Graft-versus leukemia reactions: Experimental models and clinical trials. In: Gale RP, Champlin RE, edi. Progress in bone-marrow transplantation. New-York: Alan R Liss; 1987: 219–32.
Horowitz M, Gale R, Sondel PM, Goldman JM, Kersey J, Kolb HJ, Rimm AA, Ringden O, Rozman C, Speck B, et al. Graft-versus leukemia reactions after bone marrow transplantation.Blood1990; 75: 555–562.
Goldman J, Gale R, Horowitz MM, Biggs JC, Champlin RE, Gluckman E, Hoffmann RG, Jacobsen SJ, Marmont AM, McGlave PB, et al. Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: increased risk of relapse associated with T-cell depletion.Ann Inter Med1988;108: 806–814.
Fefer A, Cheever MA, Greeberg PD. Identical-twin bone marrow (syngeneic) transplantation for hematologic cancers.J Natl Cancer Inst1986; 76: 1269–1271.
Gale RP, Horowitz MM, Ash RC, Champlin RE, Goldman JM, Rimm AA, Ringden O, Stone JA, Bortin MM. Identical twin bone marrow transplantation for leukemia.Ann Inter Med1994;120:646–652.
Weiden PL, Flournoy N, Thomas ED, Prentice R, Fefer A, Buckner CD, Storb R. Anti-leukemic effect of graft-versus-host disease in human recipients of allogeneic marrow grafts.N Engl J Med1979;300:1068–1073.
Weiden P, Sullivan K, Flournoy N, Storb R, Thomas E. Antileukemic effect of chronic graft-versus host disease: contribution to improved survival after allogeneic marrow transplantation.N Engl J Med1981;304:1529–1532.
Sullivan K, Storb R, Buckner CD, Fefer A, Fisher L, Weiden PL, Witherspoon RP, Appelbaum FR, Banaji M, Hansen J, et al. Graftversus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms.N Engl J Med1989;320:828–834.
Radich JP, Gehly G, Gooley T, Bryant E, Clift RA, Collins S, Edmands S, Kirk J, Lee A, Kessler P, et al. Polymerase chain reaction detection of the BCR-ABL fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: results and implications in 346 patients.Blood1995;85:2632–2638
Collins RH Jr, Rogers ZR, Bennett M, Kumar V, Nikein A, Fay JW. Hematologic relapse of chronic myelogenous leukemia following allogeneic transplantation: Apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppressi on.Bone Marrow Transplant1992;10:391–5.
Stavin S, Naparstek E, Nagler A, Ackerstein A, Kapelushnik Y, Or R. Allogeneic cell therapy for relapse leukemia following bone marrow transplantation with donor peripheral blood lymphocytes.Exp Hematol1995;23:1553–1562.
Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W, Ljungman P, Ferrant A, Verdonck L, NiederwieserDet al. Graft-versus-leukemia effect of donor lymphocyte infusions in marrow grafted patients.Blood1995;86:2041–2050.
Collins RH Jr, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R, Goodman SA, Wolff SN, Hu W, Verfaillie C, List A, Dalton W, Ognoskie N, Chetrit A, Antin JH, Nemunaitis J. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation.J Clin Oncol1997; 15:433–444.
Tricot G, Vesole DH, Jagannath S, Hilton J, Munshi N, BarlogieB.Graftversus-myeloma effect: Proof of principle.Blood1996;87:1196–1198.
Lokhorst HM, Schattenberg A, Cornelissen JJ, Thomas LL, Verdonck LF. Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation.Blood1997;90:4206–4211.
Rondon G, Giralt S, Huh Y, Khouri I, Andersson B, Andreeff M, Champlin R. Graft-versus-leukemia effect after allogeneic bone marrow transplantation for chronic lymphocytic leukemia.Bone Marrow Transplant1996;18:669–672.
Khouri I, Keating MJ, Korbling M, Przepiorka D, Anderlini P, O’Brien S, Ippoliti C, von Wolff B, Gajewski J, Donato M, Claxton D, Ueno N, Andersson B, Gee A, Champlin R. Transplant lite: Induction of graft vs malignancy using fludarabine based nonablative chemotherapy and allogeneic progenitor-cell transplantation as treatment for lymphoid malignancies.J Clin Oncol1998;16:2817–2824.
Ueno NT, Rondon G, Mirza NQ, Geisler DK, Anderlini P, Giralt SA, Andersson BS, Claxton DF, Gajewski JL, Khouri IF, Korbling M, Mehra RC, Przepiorka D, Rahman Z, Samuels BI, van Besien K, Hortobagyi GN, Champlin RE. Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer.J Clin Oncol1998;16:986–993.
Slavin S, Nagler A, Naparstek E, Kapelushnik J, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S. Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R. 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 diseases.Blood1998;91:756–763.
Slavin S, Strober S, Fuks Z, Kaplan HS. Long-term survival of skin allografts in mice treated with fractionated total lymphoid irradiation.Science1976;193:1252–1254.
Slavin S, Strober S, Fuks Z, Kaplan HS. Transplantation of allogeneic bone marrow without graft vs host diseae using total lymphoid irradiation.JExp Med1978;147:963–972.
Prigozhina T, Gurevitch O, Slavin S. Non-myeloablative conditioning to induce bilateral tolerance after allogeneic bone marrow transplantation in mice.Exp Hematol1999;27:1053–1510.
Morecki S, Leshem B, Weigensberg M, Bar S, Stavin S. functional clonal deletion versus active suppression in transplantation tolerance induced by total lymphoid irradiation (TLI).Transplantation1985;40:201–210.
Prigozhina T, Gurevitch O, Zhu J, Slavin S. Permanent and specific transplantation tolerance induced by a non-myeloablative treatment to a wide variety of allogeneic tissues.Transplantation1997;63:1394–1399.
Weiss L, Slavin S. Prevention and treatment of graft vs host disease by down-regulation of anti-host reactivity with veto cells of host origin.Bone Marrow Transplant1999;23:1139–1143.
Bachar-Lustig E, Rachamim N, Li HW, Lan F, Reisner Y. Megadose of T cell-depleted bone marrow overcome MHC barriers in sublethally irradiated mice.Nat Med1995; 1: 1268–1273.
Bachar-Lustig E, Li HW, Gur H, Krauthgamer R, Marcus H, Reisner Y. Induction of donor-type chimerism and transplantation tolerance across major histocompatibility barriers in sublethally irradiated mice by Sca-1(+)Lin(-) bone marrow progenitor cells: synergism with nonalloreactive (host x donor)F(1) T cells.Blood1999;94:3212–3221.
Sykes M, Szot GL, Swenson K, Pearson DA. Induction of high levels of allogeneic hematopoietic reconstitution and donor-specific tolerance without myelosuppressive conditioning.Nat Med1997;3:783–787.
Wekerle T, Kurtz J, Ito H, Ronquillo JV, Dong V, Zhao G, Shaffer J, Sayegh MH, Sykes M. Allogeneic bone marrow transplantation with costimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment.Nat Med2000;6:464–469.
Storb R, Yu C, Barnett T, Wagner J, Deeg HJ, Nash RA, Kiem HP, McSweeney P, Seidel K, Georges G, Zaucha JM. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation.Blood1997;89:3048–3054.
Storb R, Yu C, Zaucha JM, Deeg HJ, Georges G, Kiem HP, Nash RA, McSweeney PA, Wagner JL. Stable mixed hematopoietic chimerism in dogs given donor antigen, CTLA4Ig, and 100 cGy total body irradiation before and pharmacologic immunosuppression after marrow transplant.Blood1999;94:2523–2529
Antin JH, Ferrara JLM. Cytokine dysregulation and acute graft-vs-host disease.Blood1992;80:2964–2968.
Hill GR, Crawford JM, Cooke KR, Brinson YS, Pan LY, Ferrara JLM. Total body irradiation and acute graft-vs-host disease: The role of gastrointestinal damage and inflammatory cytokines.Blood1997;90:3204–3213.
Naparstek E, Or R, Nagler A, Cividalli G, Engelhard D, Aker M, Gimon Z, Manny N, Sacks T, Tochner Z, Weiss L, Samuel S, Brautbar C, Hale G, Waldmann H, Steinberg SM, Slavin S. T-cell depleted allogeneic bone marrow transplantation for acute leukemia using Campath-1 antibodies and post-transplant administration of donor’s peripheral blood lymphocytes for prevention of relapse.Br J Haematol1995;89:506–515.
Slavin S, Naparstek E, Nagler A, Ackerstein A, Samuel S, Kapelushnik J, Brautbar C, Or R. Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse post allogeneic transplantation.Blood1996;87:2195–2204.
Plunkett W, Sanders P. Metabolism and action of purine nucleoside analogs.Pharmacol Ther1991;49:239–245.
Frank DA, Mahajan S, Ritz J. Fludarabine-induced immunosuppression is associated with inhibition of STAT1 signaling.Nat Med1999;5:444–447.
Li L, Keating MJ, Plunket W, Yang LY. Fludarabine-mediated repair inhibition of cis-platin induced DNA lesions in human chronic myelogenous leukemia-blast crisis K562 cells: induction of synergistic cytotoxicity independent of reversal of apoptosis resistance.Molecular Pharmacol1997;52:798–806.
Or R, Weiss L, Teiman S, Polliack A. Fludarabine monophosphate reduces the incidence and severity of graft-versus-host disease in a murine model of bone marrow transplantation.Blood1997; 90: 471.
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. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: Harnessing graft-versus-leukemia without myeloablative therapy.Blood1997;89:4531–4536.
Slavin S, Nagler A, Naparstek E, Varadi G, Ben-Yosef R, Panighari S, Samuel S, Ackerstein A, Or R. Well tolerated nonmyeloablative fludarabine-based protocols for the treatment of malignant and nonmalignant disorders with allogeneic bone marrow and blood stem cell transplantation.Blood1999; 94(supp 1): 351a.
Nagler A, Aker M, Or R, Naparstek E, Varadi G, Brautbar C, Slavin S. Low-intensity conditioning is sufficient to ensure engraftment in matched unrelated bone marrow transplantation.Exp Hematol2001;29:362–370.
Pugatsch T, Aker M, Shapira M, Slavin S, Or R. Kinetics of engraftment post non-myeloablative stem cell transplantation (full donor chimerism).Blood2000; 96(supp 1): 172.
Nagler A, Or R, Naparstek E, Varadi G, Slavin S. Second allogeneic stem cell transplantation using non-myeloablative conditioning for patients who relapsed or developed secondary malignancies following autologous transplantation.Exp Hematol2000;28:1096–1104.
Giralt S, Thall PF, Khouri I, Wang X, Braunschweig I, Ippolitti C, Claxton D, Donato M, Bruton J, Cohen A, Davis M, Andersson BS, Anderlini P, Gajewski J, Kornblau S, Andreeff M, Przepiorka D, Ueno NT, Molldrem J, Champlin R. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation.Blood2001;97:631–637.
Childs R, Clave E, Contentin N, Jayasekara D, Hensel N, Leitman S, Read EJ, Carter C, Bahceci E, Young NS, Barrett AJ. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood transplantation: Full donor T-cell chimerism precedes alloimmune responses.Blood1999;94:3234–3241.
Carella AM, Cavaliere M, Lerma E, Ferrara R, Tedeschi L, Romanelli A, Vinci M, Pinotti G, Lambelet P, Loni C, Verdiani S, De Stefano F, Valbonesi M, Corsetti MT. Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin’s disease and non-Hodgkin’s lymphoma.J Clin Oncol2000;18:3918–3924.
Shimoni A, Giralt S, Khouri I, Champlin R. Allogeneic hematopoietic transplantation for acute and chronic myeloid leukemia: nonmyeloablative preparative regimens and induction of the graft-versusleukemia effect.Curr Oncol Rep2000;2:132–139.
Shimoni A, Anderlini P, Andersson B, Andreeff M, Braunschweig I, Claxton D, Cohen A, Donato M, Estey E, Gajewski J, Khouri I, Korbling M, Kornblau S, Molldrem J, Ueno N, Champlin R, Giralt S. Allogeneic transplantation for leukemia in patients older than 60 years: Age should not exclude treatment with non-myeloablative regimens.Blood1999; 94(supp 1), 710.
McSweeney P, Wagner J, Maloney DG, Radich J, Shizuru J, Bensinger WI, Bryant E, Chauncey TR, Flowers MED, Kaufman M, Minor CS, Nash RA, Blume K, Storb R. Outpatient PBSC allografts using immunosuppression with low dose TBI before and cyclosporine and mycophenolate mofetil after transplant.Blood1998; 92(Suppl 1) 519a.
Storb R, Yu C, Sandmaier BM, McSweeney PA, Georges G, Nash RA, Woolfrey A. Mixed hematopoietic chimerism after marrow allografts. Transplantation in the ambulatory care setting.Ann NY Acad Sci1999; 872:372–375.
Sykes M, Preffer F, McAfee S, Saidman SL, Weymouth D, Andrews DM, Colby C, Sackstein R, Sachs DH, Spitzer TR. Mixed lymphohaematopoietic chimerism and graft-versus-lymphoma effects after non-myeloablative therapy and HLA mismatched bone-marrow transplantation.Lancet 1999;353: 1755–1759.
Spitzer TR, McAfee S, Sackstein R, Colby C, Toh HC, Multani P, Saidman S, Weymouth D, Preffer F, Poliquin C, Foley A, Cox B, Dombkowski D, Andrews D, Sachs DH, Sykes M. The intentional induction of mixed chimerism and achievement of anti-tumor responses following non-myeloablative conditioning therapy and HLA-matched and mismatched donor bone marrow transplantation for refractory hematologic malignancies.Biol Blood Marrow Transplant2000; 6: 309–320.
Maris MB, Sandmaier BM, Niederwieser D, Maloney DG, McSweeney PA, Chauncey T, Shizuru J, Sahebi F, Blume K, Forman S, Storb R. The effect of donor lymphocyte infusions (DLI) on chimerism and persistent disease after nonmyeloablative hematopoietic stem cell transplant (HHSCT).Blood2000; 96(supp 1): 477a.
Molina A, McSweeney P, Maloney DG, Sandmaier B, Wagner JL, Nash R, Chauncey T, Bryant E, Storb R. Degree of early donor T-cell chimerism predicts GVHD and graft rejection in patients with nonmyeloablative hematopoietic stem cell allografts.Blood1999; 94(Suppl 1): 394a.
Slavin S, Nagler A, Shapira M, Aker M, Or R. Non-myeloablative allogeneic stem cell transplantation for the treatment of patients with chronic myeloid leukemia.Blood2000; 96(supp 1): 203.
Lalancette M, Rezvani K, Szydlo R, Mayer J, Blaise D, Zander A, Michallet M, Slavin S, Frassoni F, Gahrton G, Niederwieser N, Apperley J. Favorable outcome of non-myeloablative stem cell transplant (NMHSCT) for chronic myeloid leukemia (CML) in first chronic phase: a retrospective study of the European group for blood and marrow transplantation (EBMT).Blood2000; 96(supp 1): 545.
Champlin ER, Shimoni A, Cohen A, Arlinghous R, Siciliano M, Giralt S. FLAG-IDA, a nonablative preparative regimen with allogeneic PBSC transplantation for CML.Blood2000; 96(supp 1): 410a.
Rezvani K, Lalancette M, Szydlo R, Mackinnon S, Blaise D, Slavin S, Alessandrino EP, Michallet M, Niederwieser N, Apperley J, Frassoni F. Non-myeloablative stem cell transplant (NMHSCT) in AML, ALL,and MDS: disappointing outcome for patients with advanced phase disease.Blood2000; 96(supp 1): 479a.
Lalancette M, Michallet M, Szydlo R, Rezvani K, Mackinnon S, Blaise D, Finke J, Slavin S, Alessandrino EP, Niederwieser N, Frassoni F, Gahrton G, Apperley J. The importance of patient selection in nonmyeloablative stem cell transplant (NMHSCT) for acute and chronic leukemia, myelodysplastic syndrome and myeloma.Blood2000; 96(supp 1): 199.
Brenner M, Porcelli S. Antigen presentation: A balanced diet.Science1997;227: 332.
Nagler A, Slavin S, Varadi G, Naparstek E, Samuel S, Or R. Allogeneic peripheral blood stem cell transplantation using a fludarabine-based low intensity conditioning regimen for malignant lymphoma.Bone Marrow Transplant2000; 25: 1021–1028.
Bearman SI, Appelbaum FR, Buckner CD, Petersen FB, Fisher LD, Clift RA, Thomas ED. Regimen related toxicities in patients undergoing bone marrow transplantation.J Clin Oncol1988; 6: 1562–8.
Robinson Sp, Mackinnon S, Goldstone AH, Slavin S, Carella AM, Russell N, Taghipour G, Schmitz N. Higher than expected transplant-related mortality and relapse following non-myeloablative stem cell transplantation for lymphoma, adversely effects progression free survival.Blood2000; 96(supp 1): 554.
Khouri IF, Lee MS, Romaguera J, Mirza N, Kantarjian H, Korbling M, Albitar M, Giralt S, Samuels B, AnderliniPRodriguez J, von Wolff B, Gajewski J, Cabanillas F, Champlin R. Allogeneic hematopoietic transplantation for mantle-cell lymphoma: molecular remissions and evidence of graft-versus-malignancy.Ann Oncol1999;10: 1293–1299
Anderlini P, Giralt S, Andersson B, Ueno NT, Khouri I, Acholonu S, Cohen A, Korbling MJ, Manning J, Romaguera J, Sarris A, Rodriguez, Hagemeister F, Mclaughlin P, Cabanillas F, Champlin RE. Allogeneic stem cell transplantation with fludarabine-based, less intensive conditioning regimens as adoptive immunotherapy in advanced Hodgkin’s disease.Bone Marrow Transplant2000;26:615–620.
Giralt S, Weber D, Aleman A, Anagnastopoulos A, Anderlini P, Braunschweig I, Ontiniano M, Claxton D, Donato M, Gajewski J, Alexanian R, Champlin R. Non-myeloablative conditioning with fludarabine/melphalan for patients with multiple myeloma.Blood1999; 94(supp 1): 347.
Lalancette M, Rezvani K, Szydlo R, Mackinnon S, Juliusson G, Michallet M, Slavin S, Frassoni F, Niederwieser N, Gahrton G, Apperley J. excellent results of non-myeloablative stem cell transplant (NMHSCT) for good risk myeloma: the EBMT experience.Blood2000; 96(supp 1): 204.
Mutis T, Verdijk R, Schrama E, Esendam B, Brand A, Goulmy E. Feasibility of immunotherapy of relapse leukemia with ex vivo-generated cytotoxic T lymphocytes specific for hematopoietic system-restricted minor histocompatibility antigens.Blood1999;93:2336–2341.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer Science+Business Media New York
About this chapter
Cite this chapter
Shimoni, A., Nagler, A. (2002). Non-Myeloablative Hematopoietic Stem Cell Transplantation (NST) in the Treatment of Human Malignancies: From Animal Models to Clinical Practice. In: Bashey, A., Ball, E.D. (eds) Non-Myeloablative Allogeneic Transplantation. Cancer Treatment and Research, vol 110. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0919-6_6
Download citation
DOI: https://doi.org/10.1007/978-1-4615-0919-6_6
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5304-1
Online ISBN: 978-1-4615-0919-6
eBook Packages: Springer Book Archive