Correspondence
Umbilical-Cord Blood for Transplantation in Adults
N Engl J Med 2005; 352:935-937March 3, 2005
- Article
To the Editor:
The low rates of survival among adults who received cord-blood transplants in the two observational studies reported by Laughlin et al. and Rocha et al. (Nov. 25 issue)1,2 are not representative of what is being achieved nowadays with these transplants.3-5 Toxic effects and infections related to a slow rate of hematopoietic recovery appear to be the main factors in early transplant-related mortality and deterrents to successful cord-blood transplantation in adults. “Novel strategies to overcome this obstacle are needed,” conclude Laughlin et al.
We think the strategy we have developed fulfills this need4: low-toxicity myeloablative conditioning and coinfusion of a single cord-blood unit and a low number of highly purified peripheral-blood CD34+ cells from a third-party HLA-mismatched donor. In 25 adults with high-risk hematologic neoplasms, this strategy has resulted in minimal morbidity from toxic effects and prompt recovery of neutrophils, with a low incidence of neutropenia-related infections. Initially, engraftment derives mainly from the third-party cells, with the cord-blood transplant progressively taking over until there is complete cord-blood chimerism, which occurs within 100 days in more than 90 percent of patients. In our hands, the four-year survival rate is 65 to 82 percent.
5 ReferencesManuel N. Fernandez, M.D., Ph.D.
Carmen Regidor, M.D., Ph.D.
Rafael Cabrera, M.D., Ph.D.
Hospital Puerta de Hierro, 28035 Madrid, Spain
manueln.fernandez@uam. es 1
Laughlin MJ ,Eapen M ,Rubinstein P , et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004;351:2265-2275
Full Text | Web of Science | Medline2
Rocha V ,Labopin M ,Sanz G , et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004;351:2276-2285
Full Text | Web of Science | Medline3
Barker JN ,Weisdorf DJ ,DeFor TE , et al. Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood 2003;102:1915-1919
CrossRef | Web of Science | Medline4
Fernandez MN ,Regidor C ,Cabrera R , et al. Unrelated umbilical cord blood transplants in adults: early recovery of neutrophils by supportive co-transplantation of a low number of highly purified peripheral blood CD34+ cells from an HLA-haploidentical donor. Exp Hematol 2003;31:535-544
CrossRef | Web of Science | Medline5
Takahashi S ,Iseki T ,Ooi J , et al. Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematological malignancies. Blood 2004;104:3813-3820
CrossRef | Web of Science | Medline
To the Editor:
In their report of the results of umbilical-cord-blood transplantation in adults with acute leukemia, Rocha et al. present data provided by the Eurocord program and the European Blood and Marrow Transplant Group (EBMT). The authors compared 98 cord-blood transplants with 584 bone marrow transplants from unrelated donors; the transplantations were performed between 1998 and 2002. Surveys of marrow and cord-blood transplantations are conducted and published annually by the EBMT.1-4 During the study period, 657 cord-blood transplantations were performed, according to the EBMT; considering that only 15 to 20 percent of these transplantations were in adults, the number of these procedures performed in adults would be slightly above 100 — similar to that in the report by Rocha et al. However, 2672 bone marrow transplantations were performed during that period. After transplants in children (about 25 percent) are excluded, there remain about 2000 transplants. Even the exclusion of T-cell–depleted transplants and those for which a nonmyeloablative regimen was used (according to the study criteria) would not justify the small study number of 584. We conclude that the number of marrow transplants is underrepresented in the report by Rocha et al. and that their comparison of the results of the two procedures requires cautious interpretation.
4 ReferencesGiuseppe Bandini, M.D.
Francesca Bonifazi, M.D.
Marta Stanzani, M.D.
Institute of Hematology Seragnoli, 40138 Bologna, Italy
gbandini@alma.unibo. it 1
Gratwhol A ,Passweg J ,Baldomero H ,Hermans J ,Urbano-Ispizua A . Hematopoietic stem cell transplantation in Europe 1998. Hematol J 2000;1:333-350
CrossRef | Medline2
Gratwhol A ,Passweg J ,Baldomero H ,Urbano-Ispizua A . Hematopoietic stem cell transplantation activity in Europe 1999. Bone Marrow Transplant 2001;27:899-916
CrossRef | Web of Science | Medline3
Gratwhol A ,Baldomero H ,Passweg J ,Urbano-Ispizua A . Increasing use of reduced intensity conditioning transplants: report of the 2001 EBMT activity survey. Bone Marrow Transplant 2002;30:813-831
CrossRef | Web of Science | Medline4
Gratwhol A . Overview of transplant activity in Europe. Hematol J 2004;5:Suppl3:S29-S33
CrossRef | Medline
Author/Editor Response
Dr. Fernandez and colleagues emphasize that the relatively low rates of survival that we report among adults who received umbilical-cord-blood transplants are not representative of data from current clinical trials, which include strategies to improve the rates and kinetics of hematopoietic recovery. We concur with Dr. Fernandez and collaborators about the need to pursue innovative studies of umbilical-cord-blood grafts. We anticipate that these studies will favorably influence umbilical-cord-blood engraftment in adults and thereby improve the safety of these transplants.
Mary J. Laughlin, M.D.
Case Comprehensive Cancer Center, Cleveland, OH 44106Mary Eapen, M.D.
International Bone Marrow Transplant Registry, Milwaukee, WI 53226Pablo Rubinstein, M.D.
New York Blood Center, New York, NY 10021Author/Editor Response
We agree with Dr. Fernandez and colleagues that the results of transplantation of cord blood from unrelated donors in adults might improve with strategies that shorten the time to neutrophil recovery and decrease deaths related to infections. Indeed, we have recently shown that severe infections after transplantation of cord blood from unrelated donors are related to the duration of neutropenia.1 Thus, increasing cell dose is a major subject of current research. To achieve this goal, umbilical-cord-blood banks are currently optimizing the processes of cord-blood collection and freezing to obtain high-quality units. Moreover, other innovative research strategies to augment engraftment of cord-blood transplants from unrelated donors, besides that reported by Dr. Fernandez and colleagues, are currently under investigation.
Dr. Bandini and colleagues raise the question of the underrepresentation of bone marrow transplants from unrelated donors in adults with acute leukemia2 and conclude that our results require cautious interpretation. We have looked at the Acute Leukemia Working Party database; 2442 transplantations of bone marrow from unrelated donors were performed for primary acute leukemia (in the EBMT survey, secondary leukemia was included). According to our inclusion criteria, we excluded 536 HLA-mismatched transplants from unrelated donors, 622 bone marrow transplants from unrelated donors in children, 210 T-cell–depleted bone marrow transplants, 65 second transplants, and 50 transplants for which a reduced-intensity conditioning regimen was used. The type of conditioning was not specified in 303 cases, which were also excluded. A total of 959 patients were analyzed for overall and leukemia-free survival. These 959 patients include the 303 who were excluded, the 584 we reported on, and the 72 who had missing data, as described in the article. Overall survival and leukemia-free survival at two years among these 959 patients were similar to the reported results, varying by 1 percent.2 This result confirms that the number of bone marrow transplants from unrelated donors included in our study is representative of the overall European results.
2 ReferencesVanderson Rocha, M.D., Ph.D.
Hôpital Saint Louis, 75010 Paris, FranceMyriam Labopin, M.D.
Hôpital Saint Antoine, 75011 Paris, FranceEliane Gluckman, M.D.
Hôpital Saint Louis, 75010 Paris, Francefor the Acute Leukemia Working Party of the European Blood and Marrow Transplant Group and the Eurocord–Netcord Registry
1
Rocha V ,Chevret S ,Ionescu I , et al. Incidence and risk factors of early severe infections after unrelated cord blood transplantation: a Eurocord-Netcord analysis. Blood 2004;104:590a-590a abstract.
Web of Science2
Rocha V ,Labopin M ,Sanz G , et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004;351:2276-2285
Full Text | Web of Science | Medline
