Abstract
Preparative regimens without total body irradiation (TBI) have been reported for alternative donor hemopoietic stem cell transplants (HSCT). Between 7 September 1994 and 7 June 1999 48 patients with advanced hematologic malignancies were conditioned with thiotepa (THIO) 15 mg/kg, cyclophosphamide (CY) 150 mg/kg and antithymocyte globulin (ATG). Donors were HLA mismatched family members (1–2 antigens) (FAM) (n = 24, median age 31 years) or HLA matched unrelated donors (UD) (n = 24, median age 34 years). GVHD prophylaxis was cyclosporine and methotrexate. Stem cell source was peripheral blood (n = 8) or bone marrow (n = 40). Hematologic recovery was seen in 42/46 (91%) evaluable patients and complete chimerism in 31/37 patients (85%). Acute GVHD grades III–IV were seen in 10/46 patients surviving 10 days (21%) and extensive chronic GVHD in 2/36 patients surviving 100 days (5%). Twenty-six patients died (54%), eight of recurrent disease (17%) and 18 of transplant-related complications (37%): main causes of TRM were GVHD (15%), infections (15%) and graft failure (4%). Twenty-two patients (46%) survive with a median follow-up of 877 days (287–1840). The actuarial 3-year survival is 49% for FAM and 42% for UD transplants. Results obtained with this regimen in unrelated grafts for advanced CML (n = 15) were not significantly different when compared to 21 concurrent UD grafts for advanced CML prepared with CY-TBI. In conclusion, the combination of THIO-CY-ATG allows engraftment of alternative donor hemopoietic stem cells. Results are similar when using unrelated matched donors or partially mismatched family donors, and not significantly different when compared to patients conditioned with CY-TBI. Bone Marrow Transplantation (2000) 26, 1305–1311.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Gratwohl A, Passweg J, Baldomero H et al. Blood and marrow transplantation in Europe 1997 Bone Marrow Transplant 1999 24: 231–245
Anderson JE, Appelbaum FR, Schoch G et al. Allogeneic marrow transplantation for refractory anemia: a comparision of two preparative regimens and analysis of prognostic factors Blood 1996 87: 51–58
Klein JL, Avalos BR, Belt P et al. Bone marrow engraftment following unrelated donor transplantation utilizing busulfan and cyclophosphamide preparatory chemotherapy Bone Marrow Transplant 1996 17: 479–483
Topolsky D, Crilley P, Styler MJ et al. Unrelated donor bone marrow transplantation without T cell depletion using a chemotherapy only conditioning regimen. Low incidence of failed engraftment and severe acute GVHD Bone Marrow Transplant 1996 17: 549–554
Sahebi F, Copelan E, Crilley P et al. Unrelated allogeneic bone marrow transplantation using high-dose busulfan and cyclophosphamide (BU-CY) for the preparative regimen Bone Marrow Transplant 1996 17: 685–689
Copelan EA, Penza SL, Elder PJ et al. Influence of graft-versus-host disease on outcome following allogeneic transplantation with radiation-free preparative therapy in patients with advanced leukemia Bone Marrow Transplant 1996 18: 907–911
Bertz H, Potthoff K, Mertelsmann R et al. Busulfan/cyclophosphamide in volunteer unrelated donor (VUD) BMT: excellent feasibility and low incidence of treatment-related toxicity Bone Marrow Transplant 1997 19: 1169–1173
Patterson J, Prentice HG, Brenner MK et al. Graft rejection following HLA matched T-lymphocyte depleted bone marrow transplantation Br J Haematol 1986 63: 221–230
Eder JP, Antman K, Elias A et al. Cyclophosphamide and thiotepa with autologous bone marrow transplantation in patients with solid tumors J Natl Cancer Inst 1988 80: 1221–1226
Aversa F, Tabilio A, Velardi A et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype New Engl J Med 1998 339: 1186–1193
Eder JP, Antman K, Elias A et al. Cyclophosphamide and thiotepa with autologous bone marrow transplantation in patients with solid tumors J Natl Cancer Inst 1988 80: 1221–1225
Bacigalupo A, van Lint MT, Valbonesi M et al. Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia Blood 1996 88: 353–357
Raiola AM, van Lint MT, Lamparelli T et al. Reduced intensity thiotepa-cyclophosphamide conditioning for allogeneic hemopoietic stem cell transplants (HSCT) in patients up to 60 years of age Br J Haematol 2000 109: 716–721
Bacigalupo A, Zikos P, Van Lint MT et al. Allogeneic bone marrow or peripheral blood cell transplants in adults with hematologic malignancies: a single-center experience Exp Hematol 1998 26: 409–414
Bacigalupo A, Tedone E, Sanna MA et al. CMV infections following allogeneic BMT: risk factors early treatment and correlation with transplant related mortality Haematologica 1992 77: 507–513
Bacigalupo, S Bregante, E Tedone et al. Combined foscarnet-ganciclovir treatment for cytomegalovirus infections after allogeneic hemopoietic stem cell transplantation Transplantation 1996 62: 376–380
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 1997 19: 927–932
Santos GW, Tutchka PJ, Brookmeyer R et al. Marrow transplantation for acute non lymphocytic leukemia after treatment with busulfan and cyclophopshamide New Engl J Med 1983 309: 1347–1353
Clift RA, Buckner CD, Thomas ED et al. Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide Blood 1994 84: 2036–2043
Styler MJ, Crilley P, Biggs J et al. Hepatic dysfunction following busulfan and cyclophosphamide myeloablation: a retrospective, multicenter analysis Bone Marrow Transplant 1996 18: 171–176
Hartman AR, Williams SF, Dillon JJ . Survival, disease-free survival and adverse effects of conditioning for allogeneic bone marrow transplantation with busulfan/cyclophosphamide vs total body irradiation: a meta-analysis Bone Marrow Transplant 1998 22: 439–443
Rozman C, Carreras E, Qian C et al. Risk factors for hepatic veno-occlusive disease following HLA-identical sibling bone marrow transplants for leukemia Bone Marrow Transplant 1996 17: 75–80
Ringdén O, Remberger M, Ruutu T et al. Increased risk of chronic graft-versus-host disease, obstructive bronchiolitis, and alopecia with busulfan versus total body irradiation: long-term results of a randomized trial in allogeneic marrow recipients with leukemia Blood 1999 93: 2196–2201
Davies SM, Ramsay NKC, Klein JP et al. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia J Clin Oncol 2000 18: 340–347
Anasetti C, Beatty PG, Storb R . Effect of HLA incompatibility on graft versus host disease, relapse and survival after marrow transplantation for patients with leukemia or lymphoma Hum Immunol 1990 29: 79–91
Acknowledgements
This work was supported by Associazione Italiana Ricerca contro il Cancro (AIRC) Milano grant to AB, Associazione Italiana contro le Leucemie (AIL) Sezione Genova and Associazione Ricerca Trapianto Midollo Osseo (ARITMO) Genova. The great work of our nursing staff is gratefully acknowledged.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lamparelli, T., van Lint, M., Gualandi, F. et al. Alternative donor transplants for patients with advanced hematologic malignancies, conditioned with thiotepa, cyclophosphamide and antithymocyte globulin. Bone Marrow Transplant 26, 1305–1311 (2000). https://doi.org/10.1038/sj.bmt.1702719
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1702719
Keywords
This article is cited by
-
Comparison of reduced-toxicity conditioning protocols using fludarabine, melphalan combined with thiotepa or carmustine in allogeneic hematopoietic cell transplantation
Bone Marrow Transplantation (2021)
-
Safety and efficacy of thiotepa-based conditioning for allogeneic transplantation in AML: a survey from the ALWP of the EBMT
Bone Marrow Transplantation (2017)
-
Allogeneic transplantation following a reduced-intensity conditioning regimen in relapsed/refractory peripheral T-cell lymphomas: long-term remissions and response to donor lymphocyte infusions support the role of a graft-versus-lymphoma effect
Leukemia (2012)
-
Pre-emptive therapy of acute graft-versus-host disease: a pilot study with antithymocyte globulin (ATG)
Bone Marrow Transplantation (2001)