Advertisement

Outpatient Allografting in Hematologic Malignancies and Nonmalignant Disorders — Applying Lessons Learned in the Canine Model to Humans

  • Michael Maris
  • Rainer Storb
Part of the Cancer Treatment and Research book series (CTAR, volume 110)

Abstract

The novel allogeneic transplant approach outlined in this chapter proposes the dual concepts that currently used intensive cytoreductive conditioning programs can be successfully replaced by nonmyeloablative immunosuppression and that stem cell grafts create marrow space for engraftment through subclinical GVH reactions. Immunosuppression can be conceptually divided into two parts, one targeted exclusively towards host cells before transplantation, and the other aimed at both host and donor T lymphocytes after transplantation. The resultant effect is toeither establish mutual graft-host tolerance as reflected by stable mixed donor-host chimerism or accomplish complete donor chimerism. Preclinical studies have demonstrated the feasibility of this new approach in the context of MHC-identical transplants in young canines. Early data from the dog model of severe hereditary hemolytic anemia suggest that mixed chimerism can partially correct the phenotypic expression of disease, but that complete chimerism will be necessary to halt the continued hemolytic process of the host type minority red blood cell population. In contrast, mixed chimerism would be expected to correct disease manifestations of other severe hereditary red blood cell disorders such as sickle cell disease.

The early results in human patients with hematological malignancies have demonstrated the feasibility of establishing hematopoietic engraftment using a nonmyeloblative conditioning regimen. Using this regimen, transplants were performed in the outpatient setting, and the need for transfusion support was minimal. Preliminary information suggests that mixed chimerism does not appear to be stable in this older patient population, with most patients progressing to full donor chimerism and a small minority rejecting. Complete disease responses and molecular remissions have been observed in a significant proportion of patients, suggesting that adoptive immunotherapy may not be necessary in most cases. However, in those patients that engraft with at least mixed chimerism and develop progression of the underlying malignancy, DUs can be used for subsequent adoptive immunotherapy. The feasibility and safety of the outpatient approach for MHC-nonidentical transplantation has been demonstrated. Graft rejection appears to have been corrected by the addition of fludarabine to the nonmyeloablative conditioning regimen for the recipients of HLA-identical sibling allografts. Despite most recipients of MHC-nonidentical transplantation having sustained engraftment, some rejections have been observed. Studies are ongoing to identify the risk factors for rejection after unrelated HSCT to ensure uniform engraftment in future studies.

Keywords

Conditioning Regimen Total Body Irradiation Mixed Chimerism Marrow Graft Donor Lymphocyte Infusion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Walters MC, Patience M, Leisenring W, Eckman JR, Scott JP, Mentzer WC, Davies SC, Ohene-Frempong K, Bernaudin F, Matthews DC, Storb R, Sullivan KM: Bone marrow transplantation for sickle cell disease.N.Engl.J.Med.1996;335:369–376PubMedCrossRefGoogle Scholar
  2. 2.
    Lucarelli G, Galimberti M, Polchi P, Angelucci E, Baronciani D, Giardini C, Politi P, Durazzi SMT, Muretto P, Albertini F: Bone marrow transplantation in patients with thalassemia.N.EngLJ.Med.1990;322:417–421CrossRefGoogle Scholar
  3. 3.
    Cobbold SP, Martin G, Qin S, Waldmann H: Monoclonal antibodies to promote marrow engraftment and tissue graft tolerance.Nature1986;323:164–166PubMedCrossRefGoogle Scholar
  4. 4.
    Li H, Kaufman CL, Boggs SS, Johnson PC, Patrene KD, Ildstad ST: Mixed allogeneic chimerism induced by a sublethal approach prevents autoimmune diabetes and reverses insulitis in nonobese diabetic (NOD) mice.J.Immunol.1996;156:380–388PubMedGoogle Scholar
  5. 5.
    Colson YL, Li H, Boggs SS, Patrene KD, Johnson PC, Ildstad ST: Durable mixed allogeneic chimerism and tolerance by a nonlethal radiation-based cytoreductive approach.JImmunol.1996;157:2820–2829Google Scholar
  6. 6.
    Colson YL, Wren SM, Schuchert MJ, Patrene KD, Johnson PC, Boggs SS, Ildstad ST: A nonlethal conditioning approach to achieve durable multilineage mixed chimerism and tolerance across major, minor, and hematopoietic histocompatibility barriers.I Immunol.1995;155:4179–4188Google Scholar
  7. 7.
    Sharabi Y, Abraham VS, Sykes M, Sachs DH: Mixed allogeneic chimeras prepared by a non-myeloablative regimen: requirement for chimerism to maintain tolerance.Bone Marrow Transplant.1992;9:191–197PubMedGoogle Scholar
  8. 8.
    Tomita Y, Sachs DH, Khan A, Sykes M: Additional monoclonal antibody (mAB) injections can replace thymic irradiation to allow induction of mixed chimerism and tolerance in mice receiving bone marrow transplantation after conditioning with anti-T cell mABs and 3-Gy whole body irradiation.Transplantation1996;61:469–477PubMedCrossRefGoogle Scholar
  9. 9.
    Tomita Y, Khan A, Sykes M: Mechanism by which additional monoclonal antibody (mAB) injections overcome the requirement for thymic irradiation to achieve mixed chimerism in mice receiving bone marrow transplantation after conditioning with anti-T cell mABs and 3-Gy whole body irradiation.Transplantation1996;61:477–485PubMedCrossRefGoogle Scholar
  10. 10.
    Sykes M, Szot GL, Swenson KA, Pearson DA: Induction of high levels of allogeneic hematopoietic reconstitution and donor-specific tolerance without myelosuppressive conditioning.Nat.Med.1997;3:783–787PubMedCrossRefGoogle Scholar
  11. 11.
    Lee LA, Sergio JJ, Sykes M: Natural killer cells weakly resist engraftment of allogeneic, long-term, multilineage-repopulating hematopoietic stem cells.Transplantation1996;61:125–132PubMedCrossRefGoogle Scholar
  12. 12.
    Jankowski RA, Ildstad ST: Chimerism and tolerance: from freemartin cattle and neonatal mice to humans [Review].Hum.Immunol.1997;52:155–161PubMedCrossRefGoogle Scholar
  13. 13.
    Seledtsov VI, Seledtsova GV, Avdeev EV, Samarin DM, Kozlov VA: Induction of mixed allogeneic chimerism for leukemia.Leuk.Res.1997;21:907–909PubMedCrossRefGoogle Scholar
  14. 14.
    Koch U, Korngold R: A synthetic CD4–CDR3 peptide analog enhances bone marrow engraftment across major histocompatibility barriers.Blood1997;89:2880–2890PubMedGoogle Scholar
  15. 15.
    Iyengar AR, Bonham CA, Antonysamy MA, Subbotin VM, Khanna A, Murase N, Rao AS, Starzl TE, Thomson AW: Striking augmentation of hematopoietic cell chimerism in noncytoablated allogeneic bone marrow recipients by FLT3 ligand and tacrolimus.Transplantation1997;63:1193–1199Google Scholar
  16. 16.
    Storb R, Epstein RB, Rudolph RH, Thomas ED: Allogeneic canine bone marrow transplantation following cyclophosphamide.Transplantation1969; 7:378–386PubMedCrossRefGoogle Scholar
  17. 17.
    Storb R, Weiden PL, Graham TC, Leiner KG, Nelson N, Thomas ED: Hemopoietic grafts between DLA-identical canine littermates following dimethyl myleran. Evidence for resistance to grafts not associated with DLA and abrogated by antithymocyte serum.Transplantation1977;24:349–357PubMedCrossRefGoogle Scholar
  18. 18.
    Kawai T, Cosimi AB, Colvin RB, Powelson J, Eason J, Kozlowski T, Sykes M, Monroy R, Tanaka M, Sachs DH: Mixed allogeneic chimerism and renal allograft tolerance in Cynomolgus monkeys.Transplantation1995;59:256–262PubMedGoogle Scholar
  19. 19.
    Kimikawa M, Sachs DH, Colvin RB, Bartholomew A, Kawai T, Cosimi AB: Modifications of the conditioning regimen for achieving mixed chimerism and donor-specific tolerance in cynomolgus monkeys.Transplantation1997;64:709–716PubMedCrossRefGoogle Scholar
  20. 20.
    Watanabe K, Ito I, Otani F, Obata F, Sato K, Ishida K, Masaki Y, Maruyama S, Kashiwagi N: Factors influencing long-term operational tolerance in dogs treated with fractionated lymphoid irradiation, donor bone marrow infusion and FK506.Transplant.Proc.1995;27:221–224PubMedGoogle Scholar
  21. 21.
    Branch DR, Gallagher MT, Forman SJ, Winkler KJ, Petz LD, Blume KG: Endogenous stem cell repopulation resulting in mixed hematopoietic chimerism following total body irradiation and marrow transplantation for acute leukemia.Transplantation1982;34:226–228PubMedCrossRefGoogle Scholar
  22. 22.
    Hill RS, Petersen FB, Storb R, Appelbaum FR, Doney K, Dahlberg S, Ramberg R, Thomas ED: Mixed hematologic chimerism after allogeneic marrow transplantation for severe aplastic anemia is associated with a higher risk of graft rejection and a lessened incidence of acute graft-versus-host disease.Blood1986;67:811–816PubMedGoogle Scholar
  23. 23.
    Huss R, Deeg HJ, Gooley T, Bryant E, Leisenring W, Clift R, Buckner CD, Martin P, Storb R, Appelbaum FR: Effect of mixed chimerism on graftversus-host disease, disease recurrence, and survival after HLA-identical marrow transplantation for aplastic anemia or chronic myelogenous leukemia.Bone Marrow Transplant.1996;18:767–776PubMedGoogle Scholar
  24. 24.
    Reinsmoen NL, Jackson A, McSherry C, Ninova D, Wiesner RH, Kondo M, Krom RAF, Hertz MI, Bolman RMI, Matas AJ: Organ-specific patterns of donor antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism in lung, kidney, and liver transplant recipients.Transplantation1995;60:1546–1554PubMedCrossRefGoogle Scholar
  25. 25.
    Rugeles MT, Aitouche A, Zeevi A, Fung JJ, Watkins SC, Starzl TE, Rao AS: Evidence for the presence of multilineage chimerism and progenitors of donor dendritic cells in the peripheral blood of bone marrow-augmented organ transplant recipients.Transplantation1997;64:735–741PubMedCrossRefGoogle Scholar
  26. 26.
    Sivasai KSR, Alevy YG, Duffy BF, Brennan DC, Singer GG, Shenoy S, Lowell JA, Howard T, Mohanakumar T: Peripheral blood microchimerism in human liver and renal transplant recipients.Transplantation1997;64:427–432PubMedCrossRefGoogle Scholar
  27. 27.
    Elwood ET, Larsen CP, Maurer MH, Routenberg KL, Neylan NF, Whelchel JD, Obrien DP, Pearson TC: Microchimerism and rejection in clinical transplantation.Lancet1997;349:1358–1360PubMedCrossRefGoogle Scholar
  28. 28.
    Adams DH, Hutchinson IV: Microchimerism and graft tolerance - cause or effect.Lancet1997;349:1336–1337PubMedCrossRefGoogle Scholar
  29. 29.
    Knoop C, Andrien M, Defleur V, Antoine M, de Francquen P, Goldman M, Estenne M: Lung rejection occurs in lung transplant recipients with blood chimerism.Transplantation1997;64:167–169PubMedCrossRefGoogle Scholar
  30. 30.
    Main JM, Prehn RT: Successful skin homografts after the administration of high dosage X radiation and homologous bone marrow.J.Natl.Cancer Inst.1955;15:1023–1029PubMedGoogle Scholar
  31. 31.
    Mannick JA, Lochte HL, Jr., Ashley CA, Thomas ED, Ferrebee JW: A functioning kidney homotransplant in the dog.Surgery1959;46:821–828PubMedGoogle Scholar
  32. 32.
    Andreani M, Manna M, Lucarelli G, Tonucci P, Agostinelli F, Ripalti M, Rapa S, Talevi N, Galimberti M, Nesci S: Persistence of mixed chimerism in patients transplanted for the treatment of thalassemia.Blood1996;87:3494–3499PubMedGoogle Scholar
  33. 33.
    Yam PY, Petz LD, Knowlton RG, Wallace RB, Stock AD, de Lange G, Brown VA, Donis-Keller H, Blume KG: Use of DNA restriction fragment length polymorphisms to document marrow engraftment and mixed hematopoietic chimerism following bone marrow transplantation.Transplantation1987;43:399–407PubMedCrossRefGoogle Scholar
  34. 34.
    Kapelushnik J, Or R, Filon D, Nagler A, Cividalli G, Aker M, Naparstek E, Slavin S, Oppenheim A: Analysis of •-globin mutations shows stable mixed chimerism in patients with thalassemia after bone marrow transplantation.Blood1995;86:3241–3246PubMedGoogle Scholar
  35. 35.
    Roy DC, Tantravahi R, Murray C, Dear K, Gorgone B, Anderson KC, Nadler LM, Ritz J: Natural history of mixed chimerism after bone marrow transplantation with CD6-depleted allogeneic marrow: A stable equilibrium.Blood1990;75:296–304PubMedGoogle Scholar
  36. 36.
    .Weinberg RS, Vlachos A, Najfeld V, Galperin Y, Scalise A, Fruchtman S, Lipton JM: Disparate lympho-erythroid donor to recipient chimaerism in a beta(0)-thalassaemia bone marrow transplant recipient with red cell indices indicative of apparent full engraftment.Br.J.Haematol. 1997;99:61-63 PubMedCrossRefGoogle Scholar
  37. 37.
    Storb R, Raff RF, Graham T, Appelbaum FR, Deeg HJ, Schuening FG, Shulman H, Pepe M: Marrow toxicity of fractionated versus single dose total body irradiation is identical in a canine model.Int.J.Radiat.Oncol.Biol.Phys.1993;26:275–283PubMedCrossRefGoogle Scholar
  38. 38.
    Storb R, Raff RF, Appelbaum FR, Graham TC, Schuening FG, Sale G, Pepe M: Comparison of fractionated to single-dose total body irradiation in conditioning canine littermates for DLA-identical marrow grafts.Blood1989; 74:1139–1143PubMedGoogle Scholar
  39. 39.
    Yu C, Storb R, Mathey B, Deeg HJ, Schuening FG, Graham TC, Seidel K, Burnett R, Wagner JL, Shulman H, Sandmaier BM: DLA-identical bone marrow grafts after low-dose total body irradiation: Effects of high-dose corticosteroids and cyclosporine on engraftment.Blood1995;86:4376–4381PubMedGoogle Scholar
  40. 40.
    Keman NA, Bordignon C, Heller G, Cunningham I, Castro-Malaspina H, Shank B, Flomenberg N, Burns J, Yang SY, Black P, Collins NH, O’Reilly RJ: Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I. Analysis of risk factors and results of secondary transplants.Blood1989;74:2227–2236Google Scholar
  41. 41.
    Bjerke JW, Lorenz J, Martin PJ, Storb R, Hansen JA, Anasetti C: Treatment of graft failure with anti-CD3 antibody BC3, glucocorticoids and infusion of donor hematopoietic cells.Blood 1995;86:107a#415(Abstract)Google Scholar
  42. 42.
    Storb R, Yu C, Barnett T, Wagner JL, Deeg HJ, Nash RA, Kiem H-P, McSweeney P, Seidel K, Georges G, Zaucha JM: Stable mixed hematopoietic chimerism in dog leukocyte antigen-identical littermate dogs given lymph node irradiation before and pharmacologic immunosuppression after marrow transplantation.Blood1999;94:1131–1136PubMedGoogle Scholar
  43. 43.
    Deeg HJ, Storb R, Weiden PL, Raff RF, Sale GE, Atkinson K, Graham TC, Thomas ED: Cyclosporin A and methotrexate in canine marrow transplantation: engraftment, graft-versus-host disease, and induction of tolerance.Transplantation1982;34:30–35PubMedCrossRefGoogle Scholar
  44. 44.
    Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Doney K, Farewell V, Hansen J, Hill R, Lum L, Martin P, McGuffm R, Sanders J, Stewart P, Sullivan K, Witherspoon R, Yee G, Thomas ED: Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia.N.Engl.J.Med.1986;314:729–735PubMedCrossRefGoogle Scholar
  45. 45.
    Yu C, Seidel K, Nash RA, Deeg Hi, Sandmaier BM, Barsoukov A, Santos E, Storb R: Synergism between mycophenolate mofetil and cyclosporine in preventing graft-versus-host disease among lethally irradiated dogs given DLA-nonidentical unrelated marrow grafts.Blood1998;91:2581–2587PubMedGoogle Scholar
  46. 46.
    Yu C, Ostrander E, Bryant E, Burnett R, Storb R: Use of (CA)„ polymorphisms to determine the origin of blood cells after allogeneic canine marrow grafting.Transplantation1994;58:701–706PubMedGoogle Scholar
  47. 47.
    Yu C, Sandmaier BM, Seidel K, Storb R: Peripheral blood stem cell (PBSC) grafts from DLA-identical littermates result in enhanced mixed hematopoietic chimerism after nonmyeloablative (100 cGy) total body irradiation when compared to marrow grafts.Blood1997;90 (Suppl. 1):318b(Abstract)Google Scholar
  48. 48.
    Li Q, Kopecky KJ, Mohan A, Willman CL, Appelbaum FR, Weick JK, Issa J-PJ: Estrogen receptor methylation is associated with improved survival in adult acute myeloid leukemia.Clin.Cancer Res.1999;5:1077–1084PubMedGoogle Scholar
  49. 49.
    Barsoukov AA, Moore PF, Storb R, Santos EB, Sandmaier BM: The use of an anti-TCRa(3 monoclonal antibody to control host-versus-graft reactions in canine marrow allograft recipients conditioned with low dose total body irradiation.Transplantation1999;67:1329–1335PubMedCrossRefGoogle Scholar
  50. 50.
    Storb R, Yu C, Zaucha JM, Deeg HJ, Georges G, Kiem H-P, 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; 94:2523–2529PubMedGoogle Scholar
  51. 51.
    .Or R, Kapelushnik J, Naparstek E, Nagler A, Filon D, Oppenheim A, Amar A, Aker M, Samuel S, Slavin S: Second transplantation using allogeneic peripheral blood stem cells in a ß-thalassaemia major patient featuring stable mixed chimaerism.Br.J. Haematol. 1996;94:285-287 PubMedCrossRefGoogle Scholar
  52. 52.
    Ikehara S, Good RA, Nakamura T, Sekita K, Inoue S, Oo MM, Muso E, Ogawa K, HamashimaY:Rationale for bone marrow transplantation in the treatment of autoimmune diseases.Proc.Natl.Acad.Sci. USA1985;82:2483–2487CrossRefGoogle Scholar
  53. 53.
    Ikehara S: Autoimmune diseases as stem cell disorders: normal stem cell transplant for their treatment (Review).Irrt.J.Mol.Med.1998;1:5–16Google Scholar
  54. 54.
    Good RA, Ikehara S: Preclinical investigations that subserve efforts to employ bone marrow transplantation for rheumatoid or autoimmune diseases.J. Rheumatol.1997;24:5–12Google Scholar
  55. 55.
    Nelson JL, Torrez R, Louie FM, Choe OS, Storb R, Sullivan KM: Preexisting autoimmune disease in patients with long-term survival after allogeneic bone marrow transplantation.J.Rheumatol.1997;24:23–29Google Scholar
  56. 56.
    Weiden PL, Storb R, Graham TC, Schroeder ML: Severe hereditary haemolytic anaemia in dogs treated by marrow transplantation.Br.J. Haematol.1976;33:357–362PubMedCrossRefGoogle Scholar
  57. 57.
    Weiden PL, Hackman RC, Deeg HJ, Graham TC, Thomas ED, Storb R: Long-term survival and reversal of iron overload after marrow transplantation in dogs with congenital hemolytic anemia.Blood1981;57:66–70PubMedGoogle Scholar
  58. 58.
    Thomas ED, Buckner CD, Sanders JE, Papayannopoulou T, Borgna-Pignatti C, De Stefano P, Sullivan KM, Clift RA, Storb R: Marrow transplantation for thalassaemia.Lancet1982;ii:227–229Google Scholar
  59. 59.
    McSweeney P, Niederwieser D, Shizuru J, Molina A, Wagner J, Minor S, Radich J, Chauncey T, Hegenbart U, Maloney D, Nash R, Sandmaier B, Blume K, Storb R: Outpatient allografting with minimally myelosuppressive, immunosuppressive conditioning of low-dose TBI and postgrafting cyclosporine (CSP) and mycophenolate mofetil (MMF).Blood1999;94 (Suppl. 1):393a, #1742(Abstract)Google Scholar
  60. 60.
    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 MED, Georges GE, Grumet FC, Kiem H-P, Torok-Storb B, Yu C, Blume KG, Storb RF: Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graftversus-tumor effects.Blood2001;97:3390–3400PubMedCrossRefGoogle Scholar
  61. 61.
    Molina AJ, Storb RF: Hematopoietic stem cell transplantation in older adults, in Rowe JM, Lazarus HM, Carella AM (eds):Handbook of Bone Marrow Transplantation.London, UK, Martin Dunitz Ltd, 2000, pp 111–137Google Scholar
  62. 62.
    Molina A, McSweeney P, Maloney DG, Sandmaier B, Bensinger W, Nash R, Chauncey T, Appelbaum FR, Storb R: Non-myeloablative peripheral blood stem cell (PBSC) `allografts following cytoreductive autotransplants for treatment of multiple myeloma (MM).Blood1999;94 (Suppl. 1):347a, #155I(Abstract)Google Scholar
  63. 63.
    McSweeney P, Niederwieser D, Shizuru J, Radich J, Molina A, Hegenbart U, Chauncey T, Sandmaier B, Wolff D, Blume K, Storb R: Molecular remissions after non-myeloablative allografting for chronic myelocytic leukemia (CML).Blood1999;94 (Suppl. 1):710a, #3135(Abstract)Google Scholar
  64. 64.
    Sandmaier BM, Maloney DG, Hegenbart U, McSweeney PA, Shizuru J, Sahebi F, Chauncey T, Radich J, Maris M, Molina A, Blume K, Forman S, Niederwieser D, Storb R: Nonmyeloablative conditioning for HLA-identical related allografts for hematologic malignancies.Blood2000;96 (Part 1):479a, #2062(Abstract)Google Scholar
  65. 65.
    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 (HSCT).Blood2000;96 (Part 1):477a, #2053(Abstract)Google Scholar
  66. 66.
    Niederwieser D, Maris M, Hegenbart U, Sandmaier B, McSweeney P, Pönisch W, Uharek L, Deininger M, Edelmann J, Kamprath F, Shizuru JA, Blume K, Storb R: Allogeneic unrelated hematopoietic stem cell transplants (HSCT) after conditioning with 2 Gy total body irradiation (TBI), fludarabine (FLU) and a combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) in patients ineligible for conventional transplants.Blood2000;96 (Part 1):413a, #1778(Abstract)Google Scholar
  67. 67.
    Giralt S, Estey E, Albitar M, van Besien K, Rondón 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: Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy.Blood1997;89:4531–4536PubMedGoogle Scholar
  68. 68.
    Khouri I, Keating MJ, Przepiorka D, O’Brien S, Giralt S, Korbling M, Champlin R: Engraftment and induction of GVL with fludarabine (FAMP)based non-ablative preparative regimen in patients with chronic lymphocytic leukemia (CLL) and lymphoma.Blood1996;88:301a, #1194(Abstract)Google Scholar
  69. 69.
    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: Transplant-lite: induction of graftversus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies.I Clin.Oncol.1998;16:2817–2824Google Scholar
  70. 70.
    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: 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.Blood1998;91:756–763PubMedGoogle Scholar
  71. 71.
    Childs R, Clave E, Contentin N, Jayasekera D, Hensel N, Leitman S, Read EJ, Carter C, Bahceci E, Young NS, Barrett AJ: Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses.Blood1999;94:3234–3241PubMedGoogle Scholar
  72. 72.
    Sykes M, Preffer F, McAfee S, Saidman SL, Weymouth D, Andrews DM, Colby C, Sackstein R, Sachs DH, Spitzer TR: Mixed lymphohaemopoietic chimerism and graft-versus-lymphoma effects after non-myeloablative therapy and HLA-mismatched bone-marrow transplantation.Lancet1999;353:1755–1759PubMedCrossRefGoogle Scholar
  73. 73.
    Storb R, Yu C, Deeg HJ, Georges G, Kiem H-P, McSweeney PA, Nash RA, Sandmaier BM, Sullivan KM, Wagner JL, Walters MC: Current and future preparative regimens for bone marrow transplantation in thalassemia.Ann.NY Acad.Sci.1998;885:276–287CrossRefGoogle Scholar
  74. 74.
    Storb R, Yu C, McSweeney P: Mixed chimerism after transplantation of allogeneic hematopoietic cells, in Thomas ED, Blume KG, Forman SJ (eds):Hematopoietic Cell Transplantation 2nd Edition. Boston, Blackwell Science, 1999, pp 287–295Google Scholar
  75. 75.
    Storb R, McSweeney PA, Sandmaier BM, Nash RA, Georges G, Maloney DG, Molina A, Maris M, Woolfrey A, Chauncey T, Zaucha M, Blume KG, Shizuru J, Niederwieser D: Nonmyeloablative allogeneic hematopoietic stem cell transplantation. Hematologica(In Press)Google Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Michael Maris
  • Rainer Storb

There are no affiliations available

Personalised recommendations