Abstract
Abstract A nonmyeloablative conditioning regimen was investigated in 47 patients with hematological malignancy receiving allogeneic progenitor cells from matched, unrelated donors. The median patient age was 44 years. The majority of patients had high-risk features, including having failed a prior transplantation (29 individuals). Twenty of the transplants were mismatched for HLA class I and/or class II alleles. Recipient conditioning consisted of 20 mg CAMPATH-1H on days −8 to −4, 30 mg/m2fludarabine on days −7 to −3, and 140 mg/m2 melphalan on day −2. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine A alone. Primary graft failure occurred in only 2 of 44 evaluable patients (4.5%). Chimerism studies in 34 patients indicated that the majority (85.3%) attained initial full donor chimerism. Only 3 patients developed grade III to IV acute GVHD, and no patients have yet developed chronic extensive GVHD. The estimated probability of nonrelapse mortality at day 100 was 14.9% (95% confidence interval [CI], 4.7%-25.1%). With a median follow-up of 344 days (range, 79-830), overall and progression-free survivals at 1 year were 75.5% (95% CI, 62.8%-88.2%) and 61.5% (95% CI, 46.1%-76.8%), respectively. In summary, a nonmyeloablative regimen incorporating in vivo CAMPATH-1H is effective in promoting durable engraftment in most patients and in reducing the risk of severe GVHD following matched unrelated donor transplantation.
Bibliography
Chakraverty, R., Peggs, K., Chopra, R., Milligan, D. W., Kottaridis, P. D., Verfuerth, S., Geary, J., Thuraisundaram, D., Branson, K., Chakrabarti, S., Mahendra, P., Craddock, C., Parker, A., Hunter, A., Hale, G., Waldmann, H., Williams, C. D., Yong, K., Linch, D. C., ⦠Mackinnon, S. (2002). Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood, 99(3), 1071â1078.
Authors
21
- Ronjon Chakraverty (first)
- Karl Peggs (additional)
- Rajesh Chopra (additional)
- Donald W. Milligan (additional)
- Panagiotis D. Kottaridis (additional)
- Stephanie Verfuerth (additional)
- Johanne Geary (additional)
- Dharsha Thuraisundaram (additional)
- Kate Branson (additional)
- Suparno Chakrabarti (additional)
- Premini Mahendra (additional)
- Charles Craddock (additional)
- Anne Parker (additional)
- Ann Hunter (additional)
- Geoff Hale (additional)
- Herman Waldmann (additional)
- Catherine D. Williams (additional)
- Kwee Yong (additional)
- David C. Linch (additional)
- Anthony H. Goldstone (additional)
- Stephen Mackinnon (additional)
References
35
Referenced
300
10.1200/JCO.1997.15.5.1767/ J Clin Oncol. / Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. by Szydlo (1997)10.1182/blood.V93.2.467/ Blood. / Comparison of immune reconstitution after unrelated and related T-cell-depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions. by Small (1999)10.1046/j.1365-2141.1999.01229.x/ Br J Haematol. / Infections in adults undergoing unrelated donor bone marrow transplantation. by Williamson (1999)10.1038/sj.bmt.1702226/ Bone Marrow Transplant. / Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection. by Einsele (2000)10.1182/blood.V95.7.2219/ Blood. / Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the national marrow donor program. by McGlave (2000)10.1182/blood.V97.6.1572/ Blood. / Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. by Cornelissen (2001)10.1182/blood.V92.10.3515/ Blood. / Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. by Petersdorf (1998){'key': '2020021219220906600_B8', 'first-page': '3996', 'article-title': 'T-cell depletion of bone marrow transplants for leukemia from donors other than HLA-identical siblings: advantage of T-cell antibodies with narrow specificities.', 'volume': '95', 'author': 'Champlin', 'year': '2000', 'journal-title': 'Blood.'}/ Blood. / T-cell depletion of bone marrow transplants for leukemia from donors other than HLA-identical siblings: advantage of T-cell antibodies with narrow specificities. by Champlin (2000)10.1200/JCO.1998.16.8.2817/ J Clin Oncol. / Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. by Khouri (1998)10.1182/blood.V91.3.756/ Blood. / 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. by Slavin (1998)10.1182/blood.V94.9.3234/ Blood. / Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. by Childs (1999)10.1182/blood.V97.3.631/ Blood. / Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. by Giralt (2001)10.1111/j.1749-6632.1999.tb08481.x/ Ann N Y Acad Sci. / Mixed hematopoietic chimerism after marrow allografts: transplantation in the ambulatory care setting [discussion appears in Ann N Y Acad Sci. 1999;872:375-376]. by Storb (1999)10.1182/blood.V96.7.2419/ Blood. / In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. by Kottaridis (2000)10.1182/blood.V95.7.2240/ Blood. / Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation. by Broers (2000)10.1016/S0198-8859(98)00129-3/ Hum Immunol. / A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors. Quality Assurance and Donor Registries Working Groups of the World Marrow Donor Association. by Hurley (1999)10.1038/332323a0/ Nature. / Reshaping human antibodies for therapy. by Riechmann (1988)10.1080/146532401753174061/ Cytotherapy. / Manufacture and quality control of CAMPATH-1 antibodies for clinical trials. by Phillips (2001)10.1182/blood.V83.11.3409.3409/ Blood. / Minimal residual disease is more common in patients who have mixed T-cell chimerism after bone marrow transplantation for chronic myelogenous leukemia. by Mackinnon (1994){'key': '2020021219220906600_B20', 'first-page': '825', 'article-title': '1994 Consensus Conference on Acute GVHD Grading.', 'volume': '15', 'author': 'Przepiorka', 'year': '1995', 'journal-title': 'Bone Marrow Transplant.'}/ Bone Marrow Transplant. / 1994 Consensus Conference on Acute GVHD Grading. by Przepiorka (1995)10.1200/JCO.1989.7.9.1288/ J Clin Oncol. / Regimen-related toxicity and early posttransplant survival in patients undergoing marrow transplantation for lymphoma. by Bearman (1989){'key': '2020021219220906600_B22'}10.1126/science.285.5426.412/ Science. / Prevention of graft versus host disease by inactivation of host antigen-presenting cells. by Shlomchik (1999)10.1182/blood.V89.5.1818/ Blood. / Association of HLA-C disparity with graft failure after marrow transplantation from unrelated donors. by Petersdorf (1997)10.1182/blood.V95.8.2659/ Blood. / Molecular analysis of lineage-specific chimerism and minimal residual disease by RT-PCR of p210(BCR-ABL) and p190(BCR-ABL) after allogeneic bone marrow transplantation for chronic myeloid leukemia: increasing mixed myeloid chimerism and p190(BCR-ABL) detection precede cytogenetic relapse. by Serrano (2000)10.1182/blood.V87.9.3984.bloodjournal8793984/ Blood. / Analysis of T-cell repopulation after allogeneic bone marrow transplantation: significant differences between recipients of T-cell depleted and unmanipulated grafts. by Roux (1996)10.1111/j.1365-2141.1992.tb08149.x/ Br J Haematol. / Transfer of specific immunity from donor to recipient of an allogeneic bone marrow graft: effect of conditioning on the specific immune response of the graft recipient. by Labadie (1992){'key': '2020021219220906600_B28', 'first-page': '413', 'article-title': 'T cell reconstitution after bone marrow transplantation into adult patients does not resemble T cell development in early life.', 'volume': '16', 'author': 'Storek', 'year': '1995', 'journal-title': 'Bone Marrow Transplant.'}/ Bone Marrow Transplant. / T cell reconstitution after bone marrow transplantation into adult patients does not resemble T cell development in early life. by Storek (1995)10.1182/blood.V90.2.850/ Blood. / Essential role of the thymus to reconstitute naive (CD45RA+) T-helper cells after human allogeneic bone marrow transplantation. by Heitger (1997)10.1182/blood.V97.5.1458/ Blood. / Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. by Weinberg (2001){'key': '2020021219220906600_B31', 'first-page': '1049', 'article-title': 'Melphalan alone prior to allogeneic bone marrow transplantation from HLA-identical sibling donors for hematologic malignancies: alloengraftment with potential preservation of fertility in women.', 'volume': '18', 'author': 'Singhal', 'year': '1996', 'journal-title': 'Bone Marrow Transplant.'}/ Bone Marrow Transplant. / Melphalan alone prior to allogeneic bone marrow transplantation from HLA-identical sibling donors for hematologic malignancies: alloengraftment with potential preservation of fertility in women. by Singhal (1996)10.1124/mol.52.5.798/ Mol Pharmacol. / Fludarabine-mediated repair inhibition of cisplatin-induced DNA lesions in human chronic myelogenous leukemia-blast crisis K562 cells: induction of synergistic cytotoxicity independent of reversal of apoptosis resistance. by Li (1997)10.1182/blood.V76.12.2462.2462/ Blood. / Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. by Kolb (1990)10.1038/sj.leu.2400546/ Leukemia. / Adoptive immunotherapy for relapsed multiple myeloma after allogeneic bone marrow transplantation (BMT): evidence for a graft-versus-myeloma effect. by Bertz (1997)10.1016/S0140-6736(05)60328-5/ Lancet. / Graft-versus-lymphoma effect of donor leucocyte infusion shown by real-time quantitative PCR analysis of t(14;18). by Mandigers (1998)
Dates
| Type | When |
|---|---|
| Created | 23 years, 1 month ago (July 27, 2002, 4:46 a.m.) |
| Deposited | 5 years, 6 months ago (Feb. 12, 2020, 3:03 p.m.) |
| Indexed | 2 weeks ago (Aug. 22, 2025, 12:45 a.m.) |
| Issued | 23 years, 7 months ago (Feb. 1, 2002) |
| Published | 23 years, 7 months ago (Feb. 1, 2002) |
| Published Print | 23 years, 7 months ago (Feb. 1, 2002) |
@article{Chakraverty_2002, title={Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen}, volume={99}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v99.3.1071}, DOI={10.1182/blood.v99.3.1071}, number={3}, journal={Blood}, publisher={American Society of Hematology}, author={Chakraverty, Ronjon and Peggs, Karl and Chopra, Rajesh and Milligan, Donald W. and Kottaridis, Panagiotis D. and Verfuerth, Stephanie and Geary, Johanne and Thuraisundaram, Dharsha and Branson, Kate and Chakrabarti, Suparno and Mahendra, Premini and Craddock, Charles and Parker, Anne and Hunter, Ann and Hale, Geoff and Waldmann, Herman and Williams, Catherine D. and Yong, Kwee and Linch, David C. and Goldstone, Anthony H. and Mackinnon, Stephen}, year={2002}, month=feb, pages={1071–1078} }