Bone marrow transplantation (BMT) was initially
developed as a means to deliver supralethal doses of chemotherapy and
radiation for the treatment of malignancies.[1,2] Myelosuppression is
the dose-limiting toxicity for numerous chemotherapeutic drugs and
whole-body irradiation. Many malignancies exhibit a steep
dose-response relationship to chemotherapy or radiotherapy. Marrow
transplantation enables doses to be escalated beyond those that
produce severe bone marrow toxicity, allowing doses of many
chemotherapeutic agents, particularly alkylating agents, and
whole-body irradiation to be increased three- to fivefold above
conventional maximally tolerated levels.
Until recently, marrow transplantation was considered a
supportive-care modality for restoring hematopoiesis. It has become
clear, however, that high-dose therapy does not eradicate the
malignancy in many patients, and that the therapeutic benefit of
allogeneic marrow transplantation relates largely to an associated
immune-mediated graft-vs-malignancy effect.
Extensive clinical and experimental data support the presence of a
graft-vs-malignancy effect (Table 1).
Most of the data relates to the effects of allogeneic
transplantation in leukemia, or graft-vs-leukemia (GVL) effects.
These include a reduced risk of relapse in transplant recipients with
acute and chronic graft-vs-host disease (GVHD)[3-5] and a higher
relapse risk after syngeneic marrow transplantation.[6-8]
T-celldepleted allotransplants are also associated with an
increased risk of relapse, particularly in patients with chronic
myelogenous leukemia (CML). The most direct evidence of GVL is the
finding that, in many patients who relapse after allogeneic
transplantation, remission can be reinduced simply by infusing
additional donor lymphocytes.[9-11]
Malignancies differ with respect to their susceptibility to GVL
effects. In both acute myelogenous leukemia (AML) and CML, syngeneic
transplants are associated with an increased rate of relapse, as
compared with transplants from human lymphocyte antigen
(HLA)identical siblings; this indicates the involvement of
allogeneic minor histocompatibility target antigens. T-lymphocytes
are critical effector cells in CML, in which T-celldepleted
transplants are associated with a fivefold increase in the risk of relapse.
Minimal residual disease can be detected (using polymerase chain
reaction [PCR]based techniques for the bcr-abl rearrangement)
in most patients with CML following high-dose chemoradiation.[12,13]
The malignant cells are eliminated in most patients who receive an
unmodified marrow graft during the first 6 months posttransplant,
presumably due to the GVL effect. With syngeneic or T-cell-depleted
marrow transplantation, GVL does not occur, and if residual leukemia
cells are demonstrated, patients generally relapse.
Approximately 70% of CML patients who relapse following
transplantation achieve a complete remission after additional donor
lymphocyte infusions.[9,14,15] Similar results have been achieved
with donor lymphocyte infusions for HLA-identical sibling or matched
unrelated donors. The best results occur when relapses occur into
chronic phase and when infusions are administered early in the course
of relapse. Responding patients generally become negative for
minimal residual leukemia cells by PCR analysis, and these responses
are usually durable.
Acute myelogenous leukemia is also subject to graft-vs-malignancy
effects, but these are not as dramatic as those observed in CML. The
relapse rate for AML is increased threefold with syngeneic
transplantation but is only modestly affected by T-cell
depletion.[18,19] Approximately one-third of patients with AML or
myelodysplasia respond to donor lymphocyte infusions, but these
remissions are generally transient, and disease typically recurs
within the following year.
Among the leukemias, acute lymphocytic leukemia (ALL) is affected the
least by GVL, possibly due to the pace of the disease and the limited
capacity of the leukemic lymphoblasts to stimulate an effective
immune response.[20,21] Only rare patients with ALL have benefited
from donor lymphocyte infusions.
Relatively few patients have received allogeneic transplants for
indolent lymphoid malignancies, but available data indicate that
potent graft-vs-malignancy effects against these disorders do occur.
Allogeneic transplants are associated with a much lower relapse rate
than purged autologous transplants for low-grade lymphoma[22,23] and
CLL.[24,25] Selected patients who have CLL, lymphoma,[27,28] or
multiple myeloma[29-31] have also responded to donor lymphocyte
infusions or modification of immunosuppressive therapy.
The relationship between the graft-vs-malignancy effect and GVHD
suggests that the target antigens for graft-vs-malignancy may be
minor histocompatibility antigens shared by the malignant cells and
the tissues involved in GVHD (Table 2).
Following donor lymphocyte infusion, many patients achieve a GVL
response, ie, remission of their leukemia, without developing GVHD.
Although this finding is consistent with the premise that different
target antigens may be involved in each process, it could also result
from greater sensitivity of leukemic cells than visceral tissues to a
common immunologic mechanism.
Graft-vs-leukemia activity may also be due to reactivity against
polymorphic hematopoietic lineage-related antigens or
leukemia-specific targets. Minor histocompatibility antigens
restricted to hematopoietic tissues have been described.[32,33] There
is little evidence of a leukemia-specific response; donor-derived
T-cell clones from allogeneic chimeras typically react against both
host normal hematopoietic cells and leukemia cells.[34-36]
Overexpressed or abnormally expressed cellular constituents may also
serve as target antigens for GVL. Proteinase-3, a serine protease
present in myeloid primary granules, is overexpressed in CML and some
cases of AML; it may serve as a target for an antileukemic immune
response. Peptide antigens derived from proteinase-3 can stimulate
generation of autologous or allogeneic T-cell cytotoxicity against
A major question is whether graft-vs-tumor effects occur in
nonhematopoietic malignancies. Pilot studies in breast cancer have
reported antitumor responses in patients with GVHD, suggesting a
graft-vs-adenocarcinoma effect.[39,40] In order to justify the added
morbidity related to allogeneic transplantation, further studies are
required to determine whether immunodominant tissue-restricted minor
histocompatibility antigens are present in nonhematopoietic tumors
and whether a clinically meaningful graft-vs-tumor effect occurs.
The effector cells producing GVHD and GVL effects are incompletely
defined. Both CD4+ and CD8+ T-cells participate in the initiation of
GVHD. Natural killer (NK) cells and other populations are
subsequently recruited, and cytokines are involved as mediators of
In animals, both CD4+ and CD8+ effectors of GVL have been described.
In most models, CD8+ cells appear to the principal effectors of GVL effects.[34,45-48]
In human BMT recipients, both CD4+ and CD8+ cytotoxic antileukemic
T-cell lines or clones have been described. In patients with CML who
received transplants, several recent studies have identified CD4+
T-cell lines or clones that either inhibit the growth of leukemia
progenitors or are directly lytic.[36,46,49,50] Natural killer cells
have also been implicated as mediators of GVL effects.[48,51-54]
After infusion of donor lymphocytes, little change in peripheral
blood counts occurs initially. However, after a median of 4 months,
responding patients may suddenly become hypoplastic, followed by
recovery of blood counts from donor-derived hematopoietic cells and a
return to complete chimerism.[9,14,55] Antileukemic effectors
presumably proliferate in vivo following the infusion, and most
likely must reach a threshold level to eradicate the leukemia cells
and the normal, host-derived hematopoietic cells.
Marrow aplasia may occur unless sufficient donor-derived normal
progenitors are present to restore hematopoiesis. Consistent with
this premise, CML patients treated during advanced relapse, in which
the marrow is completely replaced with leukemic cells, develop marrow
aplasia more frequently than do patients treated during cytogenetic
or early hematologic relapse.
Most patients who become aplastic recover after a second infusion of
donor hematopoietic stem cells from either marrow or mobilized
peripheral blood. A critical factor following donor lymphocyte
infusion is the kinetics of leukemia growth. Rapid regrowth of
leukemic cells may outpace the development of an effective immune
1. Thomas ED: Bone marrow transplantation for malignant disease. J
Clin Oncol 1:517, 1983.
2. Thomas ED: The role of bone marrow transplantation for eradication
of malignant disease. Cancer 10:1963-1969, 1969.
3. Weiden PL, Sullivan KM, Flournoy N, et al: The Seattle Marrow
Transplant Team: Antileukemic effect of chronic graft-vs-host
disease: Contribution to improved survival after allogeneic marrow
transplantation. N Engl J Med 304:1529-1532, 1981.
4. Horowitz MM, Gale RP, Sondel PM, et al: Graft-vs-leukemia
reactions after bone marrow transplantation. Blood 75:555-562, 1990.
5. Sullivan KM, Storb R, Buckner CD, et al: Graft-vs-host disease as
adoptive immunotherapy in patients with advanced hematologic
neoplasms. N Engl J Med 320:828-834, 1989.
6. Gale RP, Champlin RE: How does bone marrow transplantation cure
leukemia? Lancet 2:28-30, 1984.
7. Fefer A, Cheever MA, Greeberg PD: Identical-twin (syngeneic)
marrow transplantation for hematologic cancers. J Natl Cancer Inst
8. Gale RP, Horowitz MM, Ash RC, et al: Identical-twin bone marrow
transplants for leukemia. Ann Intern Med 120:646-652, 1994.
9. Kolb HJ, Schattenberg A, Goldman JM, et al: Graft-vs-leukemia
effect of donor lymphocyte transfusions in marrow grafted patients.
Blood 86:2041-2050, 1995.
10. Antin JH: Graft-vs-leukemia: No longer an epiphenomenon. Blood
11. Drobyski WR, Keever CA, Roth MS, et al: Salvage immunotherapy
using donor leukocyte 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, 1993.
12. Radich JP, Gehly G, Gooley T, 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. Blood 85:2632-2638, 1995.
13. Hughes TP, Morgan GJ, Martiat P, et al: Detection of residual
leukemia after bone marrow transplant for chronic myeloid leukemia:
Role of polymerase chain reaction in predicting relapse. Blood
14. Collins RH, Jr, Shpilberg 0, Drobyski WR, et al: Donor leukocyte
infusions in 140 patients with relapsed malignancy after allogeneic
bone marrow transplantation. J Clin Oncol 15:433-444, 1997.
15. Cullis JO, Jiang YZ, Schwarer AP, et al: Donor leukocyte
infusions for chronic myeloid leukemia in relapse after allogeneic
bone marrow transplantation. Blood 79:1379-1381, 1992.
16. Van Rhee F, Savage D, Blackwell J, et al: Adoptive immunotherapy
for relapse of chronic myeloid leukemia after allogeneic bone marrow
transplant: Equal efficacy of lymphocytes from sibling and matched
unrelated donors. Bone Marrow Transplant 21:1055-1061, 1998.
17. Van Rhee F, Lin F, Cullis JO, et al: Relapse of chronic myeloid
leukemia after allogeneic bone marrow transplant: The case for giving
donor leukocyte transfusions before the onset of hematologic relapse.
Blood 83:3377-3383, 1994.
18. Marmont AM, Horowitz MM, Gale RP, et al: T-cell depletion of
HLA-identical transplants in leukemia. Blood 78:2120-2130, 1991.
19. Papadopoulos EB, Carabasi MH, Castro-Malaspina H, et al:
T-cell-depleted allogeneic bone marrow transplantation as
postremission therapy for acute myelogenous leukemia: Freedom from
relapse in the absence of graft-vs-host disease. Blood 91:1083-1090, 1998.
20. Cardoso AA, Seamon MJ, Afonso HM, et al: Ex vivo generation of
human anti-pre-B leukemia-specific autologous cytolytic T cells.
Blood 90:549-561, 1997.
21. Brenner M, Porcelli S: Antigen presentation: A balanced diet.
Science 277:332, 1997.
22. Van Besien KW, Khouri IF, Giralt SA, et al: Allogeneic bone
marrow transplantation for refractory and recurrent low-grade
lymphoma: The case for aggressive management. J Clin Oncol
23. Van Besien K, Sobocinski K, Rowlings PA, et al: Allogeneic bone
marrow transplantation for low-grade lymphoma. Blood 92:1832-1836, 1998.
24. Khouri IF, Przepiorka D, Van Besien K, et al: Allogeneic blood or
marrow transplantation for chronic lymphocytic leukaemia: Timing of
transplantation and potential effect of fludarabine on acute
graft-vs-host disease. Br J Haematol 97:466-473, 1997.
25. Michallet M, Archimbaud E, Bandini G, et al: HLA-identical
sibling bone marrow transplantation in younger patients with chronic
lymphocytic leukemia. Ann Intern Med 124:311-315, 1996.
26. Rondón G, Giralt 5, Huh Y, et al: Graft-vs-leukemia effect
after allogeneic bone marrow transplantation for chronic lymphocytic
leukemia. Bone Marrow Transplant 18:669-672, 1996.
27. Van Besien KW, De Lima M, Giralt SA, et al: Management of
lymphoma recurrence after allogeneic transplantation: The relevance
of graft-vs-lymphoma effect. Bone Marrow Transplant 19:977-982, 1997.
28. Khouri I, Keating MJ, Przepiorka D, et al: Engraftment and
induction of GVL with fludarabine-based non-ablative preparative
regimen in patients with chronic lymphocytic leukemia. Blood 88(suppl
29. Lokhorst HM, Schattenberg A, Comelissen JJ, et al: Donor
leukocyte infusions are effective in relapsed multiple myeloma after
allogeneic bone marrow transplantation. Blood 90:4206-4211, 1997.
30. Tricot G, Vesole DH, Jagannath S, et al: Graft-vs-myeloma effect:
Proof of principle. Blood 87:1196-1198, 1996.
31. Verdonck LF, Lokhorst HM, Dekker AW, et al: Graft-vs-myeloma
effect in two cases. Lancet 347:800-801, 1996.
32. Goulmy E, Voogt P, Van Els C, et al: The role of minor
histocompatibility antigens in GVHD and rejection: A mini-review.
Bone Marrow Transplant 1(suppl):49-51, 1991.
33. Falkenburg JHF, Goselink HM, Van der Harst D, et al: Growth
inhibition of clonogeneic leukemic precursor cells by minor
histocompatibility antigen specific cytotoxic T lymphocytes. J Exp
Med 174:27-33, 1991.
34. Faber LM, Van der Hoeven J, Goulmy E, et al: Recognition of
clonogenic leukemic cells, remission bone marrow and HLA-identical
donor bone marrow by CD8+ or CD4+ minor histocompatibility
antigen-specific cytotoxic T lymphocytes. J Clin Invest 96:877-883, 1995.
35. Jiang Y-Z, Kanfer EJ, Macdonald D, et al: Graft-vs-leukaemia
following allogeneic bone marrow transplantation: Emergence of
cytotoxic T lymphocytes reacting to host leukaemia cells. Bone Marrow
Transplant 8:253-258, 1991.
36. Sosman JA, Oettel KR, Smith SD, et al: Specific recognition of
human leukemic cells by allogeneic T cells: II. Evidence for HLA-D
restricted determinants on leukemic cells that are cross reactive
with determinants present on unrelated nonleukemic cells. Blood
37. Molldrem JJ, Clave E, Jiang YZ, et al: Cytotoxic T lymphocytes
specific for a nonpolymorphic proteinase 3 peptide preferentially
inhibit chronic myeloid leukemia colony-forming units. Blood
38. Molldrem J, Dermime S, Parker K, et al: Targeted T-cell therapy
for human leukemia: Cytotoxic T lymphocytes specific for a peptide
derived from proteinase 3 preferentially lyse human myeloid leukemia
cells. Blood 88:2450-2457, 1996.
39. Ueno NT, Rondón G, Mirza NQ, et al: Allogeneic
peripheral-blood progenitor-cell transplantation for poor-risk
patients with metastatic breast cancer. J Clin Oncol 16:986-993, 1998.
40. Eibl B, Schwaighofer H, Nachbaur D, et al: Evidence for a
graft-vs-tumor effect in a patient treated with marrow ablative
chemotherapy and allogeneic bone marrow transplantation for breast
cancer. Blood 88:1501-1508, 1996.
41. Korngold R, Sprent J: T cell subsets and graft-vs-host disease.
Transplantation 44:335-339, 1987.
42. Korngold R, Sprent J: Variable capacity of L3 T4 + T cells to
cause lethal graft-vs-host disease across minor histocompatibility
barriers in mice. J Exp Med 165:52-64, 1987.
43. Ferrara JLM, Deeg HJ: Mechanisms of disease: Graft-vs-host
disease. N Engl J Med 324:667-674, 1991.
44. Ferrara JLM, Abhyankar S, Gilliland DG: Cytokine storm of
graft-vs-host disease: A critical effector role for interleukin-1.
Transplant Proc 25:1216-1217, 1993.
45. Faber LM, Van Luxemburg-Heijs SAP, Willemze R, et al: Generation
of leukemia-reactive cytotoxic T lymphocyte clones from the
HLA-identical bone marrow donor of a patient with leukemia. J Exp Med
46. Van der Harst D, Goulmy E, Falkenburg JHF, et al: Recognition of
minor histocompatibility antigens on lymphocytic and myeloid leukemic
cells by cytotoxic T-cell clones. Blood 83:1060-1066, 1994.
47. Truitt RL, Atasoylu AA: Contribution of CD4+ and CD8+ T cells to
graft-vs-host disease and graft-vs-leukemia reactivity after
transplantation of MHC-compatible bone marrow. Bone Marrow Transplant
48. Okunewick IP, Kociban DL, Machen LL, et al: Evidence for a
possible role of Asialo-GM 1-positive cells in the graft-vs-leukemia
repression of a murine type-C retroviral leukemia. Bone Marrow
Transplant 16:451-456, 1995.
49. Jiang Y-Z, Barrett AJ: Cellular and cytokine mediated effects of
CD4-positive lymphocyte lines generated in vitro against chronic
myelogenous leukemia. Exp Hematol 23:1167-1172, 1995.
50. Jiang YZ, Mavroudis D, Dermime S, et al: Alloreactive CD4+ T
lymphocytes can exert cytotoxicity to chronic myeloid leukaemia cells
processing and presenting exogenous antigen. Br J Haematol
51. Jiang YZ, Barrett AJ, Goldman JM, et al: Association of natural
killer cell immune recovery with a graft-vs-leukemia effect
independent of graft-vs-host disease following allogeneic bone marrow
transplantation. Ann Hematol 74:l-6, 1997.
52. Zeis M, Uharek L, Glass B, et al: Allogeneic NK cells as potent
antileukemic effector cells after allogeneic bone marrow
transplantation in mice. Transplantation 59:1734-1736, 1995.
53. Glass B, Uharek L, Zeis M, et al: Graft-vs-leukaemia activity can
be predicted by natural cytotoxicity against leukaemia. Br J Haematol
54. Hauch M, Gazzola MV, Small T, et al: Anti-leukemia potential of
interleukin-2 activated natural killer cells after bone marrow
transplantation for chronic myelogenous leukemia. Blood 75:2250-2262, 1990.
55. Giralt SA, Champlin RE: Leukemia relapse after allogeneic bone
marrow transplantation: A review. Blood 84:3603-3612, 1994.
56. Hoffmann T, Theobald M, Bunjes D, et al: Frequency of bone marrow
T-cells responding to HLA-identical non-leukemic and leukemic
stimulator cells. Bone Marrow Transplant 12:1-8, 1993.
57. Keil F, Haas OA, Fritsch G, et al: Donor leukocyte infusion for
leukemic relapse after allogeneic marrow transplantation: Lack of
residual donor hematopoiesis predicts aplasia. Blood 89:3113-3117, 1997.
58. MacKinnon S, Papadopoulos EB, Carabasi MH, et al: Adoptive
immunotherapy evaluating escalating doses of donor leukocytes for
relapse of chronic myeloid leukemia after bone marrow
transplantation: Separation of graft-vs-leukemia responses from
graft-vs-host disease. Blood 86:1261-1268, 1995.
59. Bacigalupo A, Soracco M, Vassallo F, et al: Donor lymphocyte
infusions (DLI) in patients with chronic myeloid leukemia following
allogeneic bone marrow transplantation. Bone Marrow Transplant
60. Rabman SL, Mahendra P, Nacheva E, et al: Achievement of complete
cytogenetic remission after two very low-dose donor leucocyte
infusions in a patient with extensive cGVHD relapsing in accelerated
phase post allogeneic BMT for CML. Bone Marrow Transplant 21:955-956, 1998.
61. Giralt S, Hester J, Huh Y, et al: CD8+ depleted donor lymphocyte
infusion as treatment for relapsed chronic myelogenous leukemia after
allogeneic bone marrow transplantation: Graft vs leukemia without
graft vs host disease. Blood 86:4337-4343, 1995.
62. Alyea EP, Soiffer RI, Canning C, et al: Toxicity and efficacy of
defined doses of CD4+ donor lymphocytes for treatment of relapse
after allogeneic bone marrow transplant. Blood 91:3671-3680, 1998.
63. Bonini C, Ferrari G, Verzeletti S, et al: HSV-TK gene transfer
into donor lymphocytes for control of allogeneic graft-vs-leukemia.
Science 276:1719-1724, 1997.
64. Munshi NC, Govindarajan R, Drake R, et al: Thymidine kinase (TK)
gene-transduced human lymphocytes can be highly purified, remain
fully functional, and are killed efficiently with ganciclovir. Blood
65. Tiberghien P, Reynolds CW, Keller J, et al: Ganciclovir treatment
of herpes simplex thymidine kinase-transduced primary T lymphocytes:
An approach for specific in vivo donor T-cell depletion after bone
marrow transplantation. Blood 84:1333-1341, 1994.
66. Cavazzana-Calvo M, Stephan JL, Samacki S, et al: Attenuation of
graft-vs-host disease and graft rejection by ex vivo immunotoxin
elimination of alloreactive T cells in an H-2 haplotype disparate
mouse combination. Blood 83:288-298, 1994.
67. Mavroudis DA, Dermime S, Molldrem J, et al: Specific depletion of
alloreactive T cells in HLA-identical siblings: A method for
separating graft-vs-host and graft-vs-leukaemia reactions. Br J
Haematol 101:565-570, 1998.
68. Ship AM, Carter R, Murray T, et al: Irradiated donor lymphocyte
infusion, a novel approach to prevent graft failure during allogeneic
bone marrow transplant (abstract). Proc Am Soc Clin Oncol 17:74a, 1998.
69. Rooney CM, Smith CA, Ng CYC, et al: Use of gene-modified
virus-specific T lymphocytes to control Epstein-Barr-virus-related
lymphoproliferation. Lancet 345:9-13, 1995.
70. Walter EA, Greenberg PD, Gilbert MJ, et al: Reconstitution of
cellular immunity against cytomegalovirus in recipients of allogeneic
bone marrow by transfer of T-cell clones from the donor. N Engl J Med
71. Smit WM, Rijnbeek M, Van Bergen CAM, et al: Generation of
leukemia-reactive cytotoxic T lymphocytes from HLA-identical donors
of patients with chronic myeloid leukemia using modifications of a
limiting dilution assay. Bone Marrow Transplant 21:553-560, 1998.
72. Champlin RE: Separation of graft-vs-host disease and
graft-vs-leukemia against chronic myelogenous leukemia. Exp Hematol
73. Giralt S, Gajewski J, Khouri I, et al: Induction of
graft-vs-leukemia as primary treatment of chronic myelogenous
leukemia. Blood 90(suppl 1):1857a, 1997.
74. Khouri I, Keating M, Korbling M, et al: Transplant lite:
Induction of graft-vs-leukemia using fludarabine-based nonablative
chemotherapy and allogeneic blood progenitor cell transplantation as
treatment for lymphoid malignancies. J Clin Oncol 16:2817-2824, 1998.
75. Slavin S, Nagler A, Naparstek E, et al: Nonmyeloablative stem
cell transplantation and cell therapy as an alternative to
conventional bone marrow transplantation with lethal cytoreduction
for the treatment of malignant and nonmalignant hematologic diseases.
Blood 91:756-763, 1998.
76. Storb R, Yu C, Wagner JL, et al: Stable mixed hematopoietic
chimerism in DLA-identical litter mate dogs given sublethal total
body irradiation before and pharmacological immunosuppression after
marrow transplantation. Blood 89:3048-3054, 1997.
77. Antin Jill, Ferrara JLM: Cytokine dysregulation and acute
graft-vs-host disease. Blood 80:2964-2968, 1992.
78. Hill GR, Crawford JM, Cooke KR, et al: Total body irradiation and
acute graft-vs-host disease: The role of gastrointestinal damage and
inflammatory cytokines. Blood 90:3204-3213, 1997.
79. Giralt S, Estey E, Albitar M, et al: Engraftment of allogeneic
hematopoietic progenitor cells with purine analog-containing
chemotherapy: Harnessing graft-vs-leukemia without myeloablative
therapy. Blood 89:4531-4536, 1997.
80. Bensinger WI, Buckner CD, Anasetti C, et al: Allogeneic marrow
transplantation for multiple myeloma: An analysis of risk factors on
outcome. Blood 88:2787-2793, 1996.
81. Gahrton G, Tura S, Ljungman P, et al: Prognostic factors in
allogeneic bone marrow transplantation for multiple myeloma. J Clin
Oncol 13:1312-1322, 1995.
82. Giralt S, Cohen A, Mehra R, et al: Preliminary results of
fludarabine/melphalan or 2CDA/melphalan as preparative regimens for
allogeneic progenitor cell transplantation in poor candidates for
conventional myeloablative conditioning. Blood 90:1853a, 1997.
83. McSweeny PA, Wagner JL, Maloney DG, et al: Outpatient PBSC
allografts using immunosuppression with low dose TBI before, and
cyclosporine and mycophenolate mofetil after transplant. Blood
92(suppl 1):519a , 1998.
84. Kelemen E, Masszi T, Reményi P, et al: Reduction in the
frequency of transplant-related complications in patients with
chronic myeloid leukemia undergoing BMT preconditioned with a new,
non-myeloablative drug combination. Bone Marrow Transplant
85. Bacigalupo A, Van Lint MT, Occhini D, et al: Increased risk of
leukemia relapse with high-dose cyclosporine A after allogeneic
marrow transplantation for acute leukemia. Blood 77:1423-1428, 1991.