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Comparing Unrelated Donor to Sibling Donor Transplant

Consideration of an unrelated donor or cord blood transplant is appropriate for any patient who is in need of an allogeneic hematopoietic cell transplant but has no matching sibling or other related donor available. Unrelated donor transplant outcomes have improved in the last decade and some studies have shown similar outcomes for unrelated donor and sibling donor transplantation in several diseases. Some of these studies are discussed below. For a discussion of key factors in improved unrelated donor outcomes, see Improvements in Unrelated Donor Transplantation.

Acute leukemias — Adult

The acute leukemias -- acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) -- are the top two leading indications for allogeneic hematopoietic cell transplantation in adults. For details, see Outcomes and Trends and Trends in Allogeneic Transplants.

For adults with acute leukemias, several recent smaller studies have demonstrated similar survival in transplants using related or unrelated donors. A 2007 study of 64 acute leukemia patients in first or second remission undergoing myeloablative transplant with busulfan, fludarabine and 400 cGy total-body irradiation found no significant difference in two-year disease-free survival (DFS) between related donor and unrelated donor transplantation (77% vs. 71%, respectively). [1]

In a 2007 study of 105 patients aged 16-59 years with AML, no significant difference was found in five-year DFS between related and unrelated donor transplantation in good-risk patients (40% vs. 62%, respectively; p=0.2). Similarly, no significant difference in five-year DFS was found between related and unrelated donor recipients with poor-risk prognostic factors (25% vs. 21%, respectively; p=0.2). [2]

A study of reduced-intensity transplantation in elderly patients (median age 60 years; range 44-70) with secondary AML or myelodysplastic syndrome has also produced similar outcomes between related and unrelated donors. All patients were in high-risk categories (high comorbidities or relapse after prior autologous transplantation) and therefore ineligible for standard myeloablative preparative regimens. Two-year overall survival in these patients did not differ between related and unrelated donors (25% vs. 39%, respectively; p=ns). [3]

A study of 264 adult patients who received a myeloablative allogeneic transplant for ALL at nine centers, 1990-2002, showed that for transplants performed in 1st complete remission, 5-year disease-free survival was similar for unrelated (45%) and related donor (42%) transplants. Transplant-related mortality was also similar. [4]

In a study of 127 adult patients with poor-risk ALL who had unrelated donor transplants, 1988-1999, Cornelissen et al found overall survival at 2 years was 40% and DFS was 37% for transplants performed during CR1. [5] The authors indicate these results compare favorably to results obtained with chemotherapy alone and match results for HLA-identical sibling donor transplants.

A review of 46 patients with Philadelphia chromosome-positive ALL transplanted in the Nagoya Blood and Marrow Transplantation Group between 1981 and 2000 found that while donor type had a significant effect on treatment-related mortality, it was not statistically significant for DFS. [6]

Acute leukemias — Pediatric

Unrelated donor transplants for pediatric patients with ALL can achieve at least equal survival to transplants using matched sibling donors. [7,8] In a study of 65 pediatric patients transplanted in 2nd remission at 7 centers, 5-year event-free survival was 39% for sibling donor transplants and 54% for unrelated donor transplants. [7]

A 2006 study of 267 children with acute leukemias (ALL or acute myelogenous leukemia) found no differences in long-term overall survival and DFS in children receiving related donor grafts as compared to children receiving unrelated donor grafts. Three-year disease-free survival in patients transplanted in first complete remission (CR) was 49% (sibling) and 54% (unrelated donor). Overall survival and DFS were significantly higher in children transplanted in first CR compared with those transplanted in second remission or relapse. [9]

Myelodysplastic syndromes (MDS)

In patients with less advanced MDS (<5% blasts in the marrow), 3-year survival rates of 70% for HLA-identical related donor and 65% for unrelated donor transplants can be achieved. [10] For patients with more advanced disease, survival is lower and the difference between related donor and unrelated donor transplant outcomes is larger: 40-45% for related and 25-30% for unrelated donor transplants.

Chronic myelogenous leukemia (CML)

The two studies described here show that outcomes can be similar for transplants using unrelated donors and sibling donors and that earlier transplants result in better outcomes. These results must be weighed against the potential benefits of imatinib therapy — see the discussion in Transplant Outcomes by Disease and Disease Stage.

In a study of 141 patients with CML in 1st chronic phase, Davies et al [11] found no significant difference in 5-year survival:

58% for matched sibling donor transplant recipients.
53% for unrelated donor transplant recipients.
Patients who underwent transplantation within 1 year of diagnosis had a significantly higher survival rate than patients transplanted later than 1 year following diagnosis (76% vs. 70%). The difference between the related and unrelated transplant recipients was not significant.

In a prospective comparison of 2464 unrelated donor transplants with 450 matched sibling donor transplants for CML, Weisdorf et al [12] found that unrelated donor transplantation for early chronic phase CML yields survival and disease-free survival (DFS) approaching that of matched sibling transplantation. For transplants performed during chronic phase within 1 year of diagnosis, 5-year DFS was similar or only slightly inferior:

For patients younger than 30, 61% for unrelated and 68% for sibling donor transplants
Patients age 30 to 40, 57% for unrelated and 67% for sibling donor transplants
For patients older than 40, 46% for unrelated and 57% for sibling donor transplants

Results also showed that a delay in transplantation may compromise unrelated donor transplant outcomes to a greater extent than sibling donor outcomes.

Inherited immune diseases

A review of 94 children within inherited hematological diseases transplanted at Hospital Necker, Paris, engraftment, incidence of GVHD and survival were all similar for matched sibling donor transplants and unrelated donor transplants at 0-1 HLA class I mismatch, and for haploidentical related donor transplants with at least a 7 of 10 HLA match. [13]

A comparison of matched sibling donor, other related donor and unrelated donor transplants for Wiskott-Aldrich syndrome (WAS) found that for patients younger than age 5, survival for unrelated donor transplants was similar to that for HLA-identical sibling transplants. Overall, the 5-year probability of survival was 87% for transplants using sibling donors, 71% with unrelated donors and 52% with other related donors. [14] A 2006 study of 23 pediatric patients with WAS had similar results, with overall survival of 71% and 78%, respectively, for transplants using related and unrelated donors (p=ns). [15]

Severe combined immune deficiency (SCID) patients undergoing matched unrelated donor transplant have better survival than patients who receive mismatched related grafts, according to a 2006 study published in JAMA. This retrospective study analyzed the medical records of 94 infants with SCID who received marrow transplants between 1990-2004 at two pediatric referral centers. Two-year overall survival (OS) was best in patients receiving matched related transplants (92%). Two-year OS of matched unrelated transplant recipients was significantly higher than mismatched related transplant recipients (81% vs. 53%, respectively; p=0.03). [16]

Severe thalassemia

Allogeneic hematopoietic cell transplantation is the only curative option for patients with beta-thalassemia major. [17] Related-donor transplantation has been used to treat thalassemia for decades, and is the preferred treatment in this pediatric population. In the last several years, there has been a steady increase in the use of unrelated donor transplantation for severe thalassemia, and the first results show no significant difference between related and unrelated donors.

In a 2006 study of 49 pediatric thalassemia patients, two-year event-free survival for related and unrelated donors was 82% and 71%, respectively (p=ns). [18] A 2007 study of 20 thalassemia patients receiving a reduced toxicity conditioning regimen of fludarabine and busulfan found excellent survival in both groups at 39 months (100%). [17]

Severe aplastic anemia

Matched related donor hematopoietic cell transplantation is the treatment of choice for pediatric patients with severe aplastic anemia (SAA). A 2006 study of 36 pediatric SAA patients demonstrated no significant difference in four-year overall survival between related and unrelated donors (93% vs. 89%, respectively; p=ns). [19]

References

Russell JA, Savoie ML, Balogh A, et al. Allogeneic transplantation for adult acute leukemia in first and second remission with a novel regimen incorporating daily intravenous busulfan, fludarabine, 400 cGy total-body irradiation, and thymoglobulin. Biol Blood Marrow Transplant. 2007; 13(7):814-821.
http://www.bbmt.org/article/PIIS1083879107001978/abstract
Moore J, Nivison-Smith I, Goh K, et al. Equivalent survival for sibling and unrelated donor allogeneic stem cell transplantation for acute myelogenous leukemia. Biol Blood Marrow Transplant. 2007; 13(5):601-607.
http://www.bbmt.org/article/PIIS1083879107001188/abstract
Kröger N, Shimoni A, Zabelina T, et al. Reduced-toxicity conditioning with treosulfan, fludarabine and ATG as preparative regimen for allogeneic stem cell transplantation (alloSCT) in elderly patients with secondary acute myeloid leukemia (sAML) or myelodysplastic syndrome (MDS). Bone Marrow Transplant. 2006; 37(4):339-344.
http://www.nature.com/bmt/journal/v37/n4/full/1705259a.html
Kiehl MG, Kraut L, Schwerdtfeger R, et al. Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: No difference in related compared with unrelated transplant in first complete remission. J Clin Oncol. 2004; 22(14):2816-2825.
http://jco.ascopubs.org/cgi/content/full/22/14/2816
Cornelissen JJ, Carston M, Kollman C, et al. Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood. 2001; 97(6):1572-1577.
http://www.bloodjournal.org/cgi/content/full/97/6/1572
Iida H, Sao H, Kitaori K, et al. Twenty years' experience in allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in the Nagoya Blood and Marrow Transplantation Group. Int J Hematol. 2004; 79(1):79-84.
http://cardenjennings.metapress.com/link.asp?id=394dp67qff5bjmrb
Saarinen-Pihkala UM, Gustafsson G, Ringdén O, et al. No disadvantage in outcome of using matched unrelated donors as compared with matched sibling donors for bone marrow transplantation in children with acute lymphoblastic leukemia in second remission. J Clin Oncol. 2001; 19:3406-3414.
http://www.jco.org/cgi/content/abstract/19/14/3406
Gustafsson A, Remberger M, Winiarski J, Ringden O. Unrelated bone marrow transplantation in children: outcome and a comparison with sibling donor grafting. Bone Marrow Transplant. 2000; 25(10):1059-65.
http://www.nature.com/bmt/journal/v25/n10/full/1702400a.html
Eapen M, Rubinstein P, Zhang MJ, et al. Comparable long-term survival after unrelated and HLA-matched sibling donor hematopoietic stem cell transplantations for acute leukemia in children younger than 18 months. J Clin Oncol. 2006; 24(1):145-151.
http://www.jco.org/cgi/content/abstract/24/1/145
Deeg HJ, Appelbaum FR. Hemopoietic stem cell transplantation for myelodysplastic syndrome. Curr Opin Oncol. 2000; 12(2):116-120.
http://www.co-oncology.com/pt/re/cooncology/abstract.00001622-200003000-00003.htm
Davies SM, DeFor TE, McGlave PB, et al. Equivalent outcomes in patients with chronic myelogenous leukemia after early transplantation of phenotypically matched bone marrow from related or unrelated donors. Am J Med. 2001; 110(5):339-346.
http://dx.doi.org/10.1016/S0002-9343(01)00629-5
Weisdorf DJ, Anasetti C, Antin JH, et al. Allogeneic bone marrow transplantation for chronic myelogenous leukemia: comparative analysis of unrelated versus matched sibling donor. Blood. 2002; 99:1971-1977.
http://www.bloodjournal.org/cgi/content/full/99/6/1971
Caillat-Zucman S, Le Deist F, Haddad E, et al. Impact of HLA matching on outcome of hematopoietic stem cell transplantation in children with inherited diseases: a single-center comparative analysis of genoidentical, haploidentical or unrelated donors. Bone Marrow Transplant. 2004; 33:1089-1095.
http://www.nature.com/bmt/journal/v33/n11/abs/1704510a.html
Filipovich AH, Stone JV, Tomany SC, et al. Impact of donor type on outcome of bone marrow transplantation for Wiskott-Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program. Blood. 2001; 97(6):1598-1603.
http://www.bloodjournal.org/cgi/content/full/97/6/1598
Pai S-Y, DeMartiis D, Forino C, et al. Stem cell transplantation for the Wiskott–Aldrich syndrome: a single-center experience confirms efficacy of matched unrelated donor transplantation. Bone Marrow Transplant. 2006; 38(10):671-679.
http://www.nature.com/bmt/journal/v38/n10/abs/1705512a.html
Grunebaum E, Mazzolari E, Porta F, et al. Bone marrow transplantation for severe combined immune deficiency. JAMA. 2006; 295(5):508-518.
http://jama.ama-assn.org/cgi/content/abstract/295/5/508
Resnick IB, Aker M, Tsirigotis P, et al. Allogeneic stem cell transplantation from matched related and unrelated donors in thalassemia major patients using a reduced toxicity fludarabine-based regimen. Bone Marrow Transplant. 2007; 40(10):957–964.
http://www.nature.com/bmt/journal/v40/n10/abs/1705826a.html
Hongeng S, Pakakasama S, Chuansumrit A, et al. Outcomes of transplantation with related- and unrelated-donor stem cells in children with severe thalassemia. Biol Blood Marrow Transplant. 2006; 12(6):683-687.
http://www.bbmt.org/article/PIIS1083879106001819/fulltext
Kennedy-Nasser AA, Leung KS, Mahajan A, et al. Comparable outcomes of matched-related and alternative donor stem cell transplantation for pediatric severe aplastic anemia. Biol Blood Marrow Transplant. 2006; 12(12):1277-1284.
http://www.bbmt.org/article/PIIS1083879106004976/abstract