Impact of Viable CD45 Cells Infused on Lymphocyte Subset Recovery after Unrelated Cord Blood Transplantation in Children

We studied lymphocyte recovery in 88 children who consecutively underwent unrelated cord blood transplantation for malignant (n = 64) or nonmalignant (n = 24) diseases. All children but 3 received myeloablative conditioning regimens with pretransplant antithymocyte globulin. Median age was 5.6 years (0.1-18 years) and median follow-up was 40 months (10-136 months). The median dose of infused viable CD45+ cells (vCD45) was 3.35 × 107/kg with a ratio infused vCD45/collected total nucleated cell at 0.46. Immunologic endpoints were: time to achieve CD3+ >500 and 1500/mm3, CD4+ >500/mm3, CD8+ >250/mm3, CD19+ >200/mm3, natural killer >100/mm3. These endpoints were analyzed through the use of cumulative curves for estimating incidence over time in the context of competing risks, and through Fine and Gray models to assess prognostic factors. The median time to reach these endpoints was 33, 97, 214, and 340 days for natural killer, B, CD8, and CD4 cells, respectively. In multivariate analysis, a high infused vCD45 cell dose improved CD3 (P = .014) and CD4 (P = .032) reconstitutions. A young recipient age also favored CD3 recovery (P = .013). With patients grouped according to vCD45 cell dose quartiles, the threshold for a better recovery was 3.35 × 107/kg. Considering the ratio vCD45/TNC, this “immune recovery based” threshold corresponds to a higher cell dose than the minimum usually recommended dose for myelogenous engraftment. This may have important implication for UCB selection. We studied lymphocyte recovery in 88 children who consecutively underwent unrelated cord blood transplantation for malignant (n = 64) or nonmalignant (n = 24) diseases. All children but 3 received myeloablative conditioning regimens with pretransplant antithymocyte globulin. Median age was 5.6 years (0.1-18 years) and median follow-up was 40 months (10-136 months). The median dose of infused viable CD45+ cells (vCD45) was 3.35 × 107/kg with a ratio infused vCD45/collected total nucleated cell at 0.46. Immunologic endpoints were: time to achieve CD3+ >500 and 1500/mm3, CD4+ >500/mm3, CD8+ >250/mm3, CD19+ >200/mm3, natural killer >100/mm3. These endpoints were analyzed through the use of cumulative curves for estimating incidence over time in the context of competing risks, and through Fine and Gray models to assess prognostic factors. The median time to reach these endpoints was 33, 97, 214, and 340 days for natural killer, B, CD8, and CD4 cells, respectively. In multivariate analysis, a high infused vCD45 cell dose improved CD3 (P = .014) and CD4 (P = .032) reconstitutions. A young recipient age also favored CD3 recovery (P = .013). With patients grouped according to vCD45 cell dose quartiles, the threshold for a better recovery was 3.35 × 107/kg. Considering the ratio vCD45/TNC, this “immune recovery based” threshold corresponds to a higher cell dose than the minimum usually recommended dose for myelogenous engraftment. This may have important implication for UCB selection. IntroductionSince initial studies reported by Kurtzberg et al. [1Kurtzberg J. Laughlin M. Graham M.L. et al.Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients.N Engl J Med. 1996; 335: 157-166Crossref PubMed Scopus (982) Google Scholar], Wagner et al. [2Wagner J.E. Rosenthal J. Sweetman R. et al.Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease.Blood. 1996; 88: 795-802PubMed Google Scholar], and Gluckman et al. [3Gluckman E. Rocha V. Boyer-Chammard A. et al.Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group.N Engl J Med. 1997; 337: 373-381Crossref PubMed Scopus (1174) Google Scholar], hematopoietic stem cell transplantation (HSCT) from an unrelated cord blood unit (UCBT) has become an accepted therapeutic strategy for children without an HLA identical donor who need an allogeneic HSCT [4Grewal S.S. Barker J.N. Davies S.M. Wagner J.E. Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood?.Blood. 2003; 101: 4233-4244Crossref PubMed Scopus (247) Google Scholar]. The increasing use of CB, relative to bone marrow transplantation (BMT), in the unrelated donor setting is explained by such reasons as noninvasive hematopoietic collection, prompt availability of UCB units, less stringent criteria for HLA matching, lower incidence and severity of graft-versus-host disease (GVHD), and overall similar outcomes with both types of grafts in children [5Rocha V. Cornish J. Sievers E.L. et al.Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia.Blood. 2001; 97: 2962-2971Crossref PubMed Scopus (662) Google Scholar, 6Eapen M. Rubinstein P. Zhang M.J. et al.Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study.Lancet. 2007; 369: 1947-1954Abstract Full Text Full Text PDF PubMed Scopus (651) Google Scholar, 7Kurtzberg J. Prasad V.K. Carter S.L. et al.Results of the Cord Blood Transplantation study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies.Blood. 2008; 112: 4318-4327Crossref PubMed Scopus (250) Google Scholar] and adults [8Laughlin M.J. 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: 2265-2275Crossref PubMed Scopus (926) Google Scholar, 9Shi-Xia X. Xian-Hua T. Xiang-Feng T. Unrelated umbilical cord blood transplantation and unrelated bone marrow transplantation in children with hematological disease: a meta-analysis.Pediatr Transplant. 2009; 13: 278-284Crossref PubMed Scopus (17) Google Scholar]. Despite the low incidence of GVHD, relapse rate of leukemia appears to be similar after UCBT or unrelated BMT [10Rocha V. Wagner Jr., J.E. Sobocinski K.A. et al.Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources.N Engl J Med. 2000; 342: 1846-1854Crossref PubMed Scopus (739) Google Scholar, 11Barker J.N. Davies S.M. DeFor T. Ramsay N.K. Weisdorf D.J. Wagner J.E. Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis.Blood. 2001; 97: 2957-2961Crossref PubMed Scopus (335) Google Scholar]. Nevertheless, UCBT remains associated with a high incidence of life-threatening infections, especially during the early posttransplant period [10Rocha V. Wagner Jr., J.E. Sobocinski K.A. et al.Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources.N Engl J Med. 2000; 342: 1846-1854Crossref PubMed Scopus (739) Google Scholar, 12Rubinstein P. Carrier C. Scaradavou A. et al.Outcomes among 562 recipients of placental-blood transplants from unrelated donors.N Engl J Med. 1998; 339: 1565-1577Crossref PubMed Scopus (1179) Google Scholar, 13Barker J.N. Hough R.E. van Burik J.A. et al.Serious infections after unrelated donor transplantation in 136 children: impact of stem cell source.Biol Blood Marrow Transplant. 2005; 11: 362-370Abstract Full Text Full Text PDF PubMed Scopus Google Scholar]. is the of and is related to recovery J. Prasad V.K. Carter S.L. et al.Results of the Cord Blood Transplantation study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies.Blood. 2008; 112: 4318-4327Crossref PubMed Scopus (250) Google Scholar, V. Gluckman E. use of umbilical cord blood hematopoietic stem Blood Marrow Transplant. Full Text Full Text PDF PubMed Scopus Google Scholar, Laughlin M. et umbilical cord blood transplantation in Blood Marrow Transplant. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar]. have lymphocyte and of recovery after UCBT K.A. et of graft-versus-host and recovery unrelated donor cord blood 2000; Google Scholar, P. et and after unrelated cord blood transplantation: a Marrow Transplant. 2000; PubMed Scopus Google Scholar, A. R. et of in children cord blood 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, cord blood transplantation in 2000; PubMed Scopus Google Scholar, T. Rocha V. et lymphocyte after related or unrelated cord blood transplantation in Eurocord J 2001; PubMed Scopus Google Scholar]. these studies may be as to of such as low of to and in of transplant and of posttransplant a analysis of lymphocyte recovery in 88 children who consecutively received UCBT in a pediatric transplant and in pediatric transplant were for the study the received HSCT with a unrelated cord blood years or less at time of in at the time of transplant for children with malignant diseases. children consecutively and these criteria and were in the of HLA and Transplant HLA was at for and of HLA of recipients and UCB was by HLA was as the of identical among were from in (n = the (n = (n = the (n = (n = (n = (n = and (n = the total nucleated cell dose for of Transplant Cell and on infused cell were by the as as by and CD45+ cells of and CD45+ cells were the as C. et in umbilical and after Marrow Transplant. 2007; PubMed Scopus Google Scholar]. this the the viable (vCD45) corresponds to viable infused cells the leukocyte this for a of viable and CD45+ cells and of cells in cord a on a on the 2001; PubMed Scopus Google Scholar, M. J. R. cell on the International of and 1998; PubMed Scopus Google Scholar]. and were on a the The strategy is from for cord blood cell of cells in cord a on a on the 2001; PubMed Scopus Google of and Blood recipients underwent blood at days months and analysis of blood was to the lymphocyte CD3+ and CD19+ and natural killer was analyzed in blood cells of recipients at days and and months and after was by of was as cells, as the of to cells, and recovery as hematopoietic recovery and with blood were for posttransplant overall relapse acute and endpoints were for clinical time to achieve a CD3+ cell >500/mm3, CD3 CD4 >500/mm3, >250/mm3, >200/mm3, and was as the that the on for incidence over the endpoints a competing patients that the of the of an after or relapse of an recovery these endpoints and endpoints for of were analyzed through the use of cumulative incidence curves for estimating incidence over time J. of in the of competing of Med. PubMed Scopus Google Scholar] and through Fine and Gray models of competing 2001; PubMed Google Scholar] to assess prognostic factors. In this of a stem cell and recovery were as competing for studied for impact on lymphocyte recovery recipient pretransplant disease or HLA or of cell conditioning or without total and These were in the analysis as as in the were with studied for impact on lymphocyte cell dose was by related and infused infused viable and CD45+ cell and infused CD3+ cell the of transplant cell dose was by multivariate of these of the was to these related studied be at the time of transplantation and the impact of on recovery a analysis at were the and the the cumulative incidence has the and Cord Blood of the 88 median age at the time of transplantation was 5.6 years years) and the median follow-up period was 40 months months). of and nonmalignant received a of (n = or a of (n = HLA identical The median dose of infused viable CD45+ a cells, and viable cells recipient × 3.35 × and × The median ratio of viable cells was and Cord Blood Median years Median Bone marrow HLA HLA HLA 3 HLA Median × Median infused × Median vCD45 infused × vCD45 Median infused × Median CD3 infused × Median infused × Median infused × patients received antithymocyte over 3 patients underwent a conditioning of were to the of and acute acute myelogenous total nucleated total All patients received antithymocyte over 3 patients underwent a conditioning of were to the of and in a Transplantation children but 3 received a myeloablative conditioning with in 3 days and and for (n = or and for (n = In antithymocyte was infused at a dose of from days to of A and to through days through through days through days through days and with malignant and nonmalignant received for a total of 3 and respectively. was with was after transplantation to median follow-up period was 40 months of and were and respectively. was of were relapse (n = infections (n = (n = (n = disease (n = and (n = The median time to reach and engraftment was days and days respectively. days after in of the patients = = = in and was in outcomes cumulative incidence curves of the patients the and cell and respectively. cells with a median time to of days and an from to median time to cells was days and cell recovery was children the early and patients the incidence that the median time to reach these endpoints were days and 340 days respectively. The of CD8+ cells to be than recovery results of and multivariate in and of multivariate infused vCD45 cell dose for cell dose × 3.35 × × by 3.35 × × × 3.35 × × The multivariate infused vCD45 cell dose for cell dose × by in a In the multivariate analysis, infused vCD45 cell dose a improved the early for cell recovery with an by × (P = the CD4 = and the cell = With patients grouped according to viable cell dose quartiles, recovery in recipient of than 3.35 × 107/kg cell after of unit This was for early CD3 = and for CD4 = and incidence of CD3 >500 and and CD4 >500 and cell recovery according to viable dose and cumulative incidence of lymphocyte recovery according to infused × × × × in vCD45 cell dose was with in this study to cell that infused and CD3+ cell (P for the of cell dose on cell recovery was infused or CD3+ cell were in the of the infused vCD45 cell infused viable cell dose recipient and cell dose recipient cell dose or CD3 cell dose recipient the for cell recovery was analyzed a better age recipient was for of = .013). of the a on cell A pretransplant was associated with an improved cell recovery of cells = cell was in children with malignant than in children without = of on cell studies have lymphocyte recovery after unrelated K.A. et of graft-versus-host and recovery unrelated donor cord blood 2000; Google Scholar, P. et and after unrelated cord blood transplantation: a Marrow Transplant. 2000; PubMed Scopus Google Scholar, A. R. et of in children cord blood 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, cord blood transplantation in 2000; PubMed Scopus Google Scholar, T. Rocha V. et lymphocyte after related or unrelated cord blood transplantation in Eurocord J 2001; PubMed Scopus Google Scholar]. Nevertheless, study may the of this through 3 We to a of 88 children who consecutively underwent without on or relapse The reported lymphocyte recovery of with the study the Eurocord UCBT recipients T. Rocha V. et lymphocyte after related or unrelated cord blood transplantation in Eurocord J 2001; PubMed Scopus Google Scholar]. These 88 were in a pediatric transplant for transplant unit and on the and infused conditioning and in recovery is to competing analyzed cumulative incidence curves for estimating incidence over time in the of competing J. of in the of competing of Med. PubMed Scopus Google Scholar, of competing 2001; PubMed Google Scholar, Zhang M.J. for the analysis and of the results of bone marrow Marrow Transplant. 2001; PubMed Scopus Google Scholar] as recommended by European Group for Blood and Marrow Transplantation R. of HSCT J. E. Gluckman E. A. T. The Stem Cell Scholar]. This a of competing than the is for in this the of after this of of competing is the for and relapse after HSCT and is to and R. of HSCT J. E. Gluckman E. A. T. The Stem Cell Scholar]. such a the of to The use of is a in children on the and this has the clinical after In in this stem cells from of recipient In this to endpoints for CD3+ cell CD3 as a early CD3 as a for lymphocyte recovery were to the lower of et in children from through years of the Group 2003; 112: Full Text Full Text PDF PubMed Scopus Google Scholar, et after hematopoietic stem cell transplantation of a of patients with 2009; PubMed Scopus Google lymphocyte recovery the as in cells cells, cells K.A. et of graft-versus-host and recovery unrelated donor cord blood 2000; Google Scholar, P. et and after unrelated cord blood transplantation: a Marrow Transplant. 2000; PubMed Scopus Google Scholar, A. R. et of in children cord blood 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, cord blood transplantation in 2000; PubMed Scopus Google Scholar, T. Rocha V. et lymphocyte after related or unrelated cord blood transplantation in Eurocord J 2001; PubMed Scopus Google Scholar]. as in stem cell the appears to than In of median time to recovery for both and cells was to reported [3Gluckman E. Rocha V. Boyer-Chammard A. et al.Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group.N Engl J Med. 1997; 337: 373-381Crossref PubMed Scopus (1174) Google Scholar, 12Rubinstein P. Carrier C. Scaradavou A. et al.Outcomes among 562 recipients of placental-blood transplants from unrelated donors.N Engl J Med. 1998; 339: 1565-1577Crossref PubMed Scopus (1179) Google cells a median of 3 months et al. K.A. et of graft-versus-host and recovery unrelated donor cord blood 2000; Google Scholar] and et al. T. Rocha V. et lymphocyte after related or unrelated cord blood transplantation in Eurocord J 2001; PubMed Scopus Google Scholar] reported a of the cell after as as This in the of the Eurocord study the time to reach the to study endpoints for cells as as for cells in study for on cell the recipient pretransplant with an in this reported in a study by et al. E. J. et after cell transplantation in children: analysis with to the of J PubMed Scopus Google Scholar]. that cell recovery in allogeneic BMT recipients with of remains early also in lymphocyte were the to In this be by the use of in the studies have that pretransplant in the early posttransplant period and with recovery for of in bone marrow 2003; PubMed Scopus Google Scholar]. of cells after allogeneic HSCT through The early the of donor cells, to J.A. R.E. cell of cells in a that is in and to 1996; Google Scholar]. The of lymphocyte cells a cell R.E. and 1997; PubMed Scopus Google Scholar, E. C. et and an a after cord blood stem cell PubMed Scopus Google Scholar]. study the of age on the cell recovery is to the recipients a better cell recovery than the of R.E. and 1997; PubMed Scopus Google also that the of viable cells was the important for the early cell and for CD4 cell infused infused cells were to lymphocyte these criteria of hematopoietic after UCBT [3Gluckman E. Rocha V. Boyer-Chammard A. et al.Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group.N Engl J Med. 1997; 337: 373-381Crossref PubMed Scopus (1174) Google Scholar, V. Cornish J. Sievers E.L. et al.Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia.Blood. 2001; 97: 2962-2971Crossref PubMed Scopus (662) Google Scholar, C. et in umbilical and after Marrow Transplant. 2007; PubMed Scopus Google Scholar, Rocha V. C. et associated with after cord blood transplantation in children with acute Blood Transplant Google Scholar, J.E. Barker J.N. DeFor et of unrelated donor umbilical cord blood in patients with malignant and nonmalignant of cell dose and HLA on and PubMed Scopus Google Scholar]. be to this is that the vCD45 cell the viable infused cells the leukocyte may be a criteria to engraftment than the cells and The high and infused dose in and × also have to the of the impact of this by the of transplants with low cell dose and a high of that criteria and to hematopoietic engraftment the is study that a minimum vCD45 cell dose of 3.35 × 107/kg at be to achieve a lymphocyte vCD45 be as a for of cell recovery and consecutively for the of life-threatening infections M. et of and lymphocyte recovery and after unrelated umbilical cord blood HLA-matched unrelated donor allogeneic transplantation in J 2004; PubMed Scopus Google Scholar, P. after unrelated cord blood 2007; Full Text Full Text PDF PubMed Scopus Google Scholar]. on the recovery of lymphocyte and on such as cell to and of This is an of the on of posttransplant and studies to better lymphocyte and for unit on hematopoietic engraftment All studies the use of a high cell the cell dose recommended for transplantation usually from to × [3Gluckman E. Rocha V. Boyer-Chammard A. et al.Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group.N Engl J Med. 1997; 337: 373-381Crossref PubMed Scopus (1174) Google Scholar, 12Rubinstein P. Carrier C. Scaradavou A. et al.Outcomes among 562 recipients of placental-blood transplants from unrelated donors.N Engl J Med. 1998; 339: 1565-1577Crossref PubMed Scopus (1179) Google Scholar, E. Rocha V. et associated with outcomes of unrelated cord blood for donor 2004; Full Text Full Text PDF PubMed Scopus Google Scholar], or at × C. et in umbilical and after Marrow Transplant. 2007; PubMed Scopus Google Scholar, J.E. Barker J.N. DeFor et of unrelated donor umbilical cord blood in patients with malignant and nonmalignant of cell dose and HLA on and PubMed Scopus Google Scholar]. were in the of viable of at this threshold of 3.35 × 107/kg at grafts at × at a clinical of this is to achieve with a unit cell by the of cells in the criteria to a transplant of less units, with the associated with higher achieve such a be such as cord blood transplantation or of of to assess in of hematopoietic and recovery J. A. et of umbilical cord blood transplantation with UCB results of a the 2003; 101: PubMed Scopus Google Scholar, S.M. of hematopoietic cell and Marrow Transplant. 2003; PubMed Scopus Google Scholar]. on have better GVHD, less and better than after J.N. Weisdorf D.J. DeFor et of HLA-matched umbilical cord blood to engraftment in adults with hematologic 2005; PubMed Scopus Google Scholar, Wagner J.E. umbilical cord blood PubMed Scopus Google Scholar, Wagner J.E. Weisdorf D.J. et of in recipients of umbilical cord blood transplant on transplantation conditioning 2009; PubMed Scopus Google Scholar, M.L. Weisdorf D.J. et graft-versus-host disease after unrelated donor umbilical cord blood transplantation: analysis of 2009; PubMed Scopus Google Scholar, Barker J. et after umbilical cord blood transplantation: in recipients of 2009; PubMed Scopus Google Scholar]. or may recovery is an that IntroductionSince initial studies reported by Kurtzberg et al. [1Kurtzberg J. Laughlin M. Graham M.L. et al.Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients.N Engl J Med. 1996; 335: 157-166Crossref PubMed Scopus (982) Google Scholar], Wagner et al. [2Wagner J.E. Rosenthal J. Sweetman R. et al.Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease.Blood. 1996; 88: 795-802PubMed Google Scholar], and Gluckman et al. [3Gluckman E. Rocha V. Boyer-Chammard A. et al.Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group.N Engl J Med. 1997; 337: 373-381Crossref PubMed Scopus (1174) Google Scholar], hematopoietic stem cell transplantation (HSCT) from an unrelated cord blood unit (UCBT) has become an accepted therapeutic strategy for children without an HLA identical donor who need an allogeneic HSCT [4Grewal S.S. Barker J.N. Davies S.M. Wagner J.E. Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood?.Blood. 2003; 101: 4233-4244Crossref PubMed Scopus (247) Google Scholar]. The increasing use of CB, relative to bone marrow transplantation (BMT), in the unrelated donor setting is explained by such reasons as noninvasive hematopoietic collection, prompt availability of UCB units, less stringent criteria for HLA matching, lower incidence and severity of graft-versus-host disease (GVHD), and overall similar outcomes with both types of grafts in children [5Rocha V. Cornish J. Sievers E.L. et al.Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia.Blood. 2001; 97: 2962-2971Crossref PubMed Scopus (662) Google Scholar, 6Eapen M. Rubinstein P. Zhang M.J. et al.Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study.Lancet. 2007; 369: 1947-1954Abstract Full Text Full Text PDF PubMed Scopus (651) Google Scholar, 7Kurtzberg J. Prasad V.K. Carter S.L. et al.Results of the Cord Blood Transplantation study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies.Blood. 2008; 112: 4318-4327Crossref PubMed Scopus (250) Google Scholar] and adults [8Laughlin M.J. 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: 2265-2275Crossref PubMed Scopus (926) Google Scholar, 9Shi-Xia X. Xian-Hua T. Xiang-Feng T. Unrelated umbilical cord blood transplantation and unrelated bone marrow transplantation in children with hematological disease: a meta-analysis.Pediatr Transplant. 2009; 13: 278-284Crossref PubMed Scopus (17) Google Scholar]. Despite the low incidence of GVHD, relapse rate of leukemia appears to be similar after UCBT or unrelated BMT [10Rocha V. Wagner Jr., J.E. Sobocinski K.A. et al.Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources.N Engl J Med. 2000; 342: 1846-1854Crossref PubMed Scopus (739) Google Scholar, 11Barker J.N. Davies S.M. DeFor T. Ramsay N.K. Weisdorf D.J. Wagner J.E. Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis.Blood. 2001; 97: 2957-2961Crossref PubMed Scopus (335) Google Scholar]. Nevertheless, UCBT remains associated with a high incidence of life-threatening infections, especially during the early posttransplant period [10Rocha V. Wagner Jr., J.E. Sobocinski K.A. et al.Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources.N Engl J Med. 2000; 342: 1846-1854Crossref PubMed Scopus (739) Google Scholar, 12Rubinstein P. Carrier C. Scaradavou A. et al.Outcomes among 562 recipients of placental-blood transplants from unrelated donors.N Engl J Med. 1998; 339: 1565-1577Crossref PubMed Scopus (1179) Google Scholar, 13Barker J.N. Hough R.E. van Burik J.A. et al.Serious infections after unrelated donor transplantation in 136 children: impact of stem cell source.Biol Blood Marrow Transplant. 2005; 11: 362-370Abstract Full Text Full Text PDF PubMed Scopus Google Scholar]. is the of and is related to recovery J. Prasad V.K. Carter S.L. et al.Results of the Cord Blood Transplantation study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies.Blood. 2008; 112: 4318-4327Crossref PubMed Scopus (250) Google Scholar, V. Gluckman E. use of umbilical cord blood hematopoietic stem Blood Marrow Transplant. Full Text Full Text PDF PubMed Scopus Google Scholar, Laughlin M. et umbilical cord blood transplantation in Blood Marrow Transplant. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar]. have lymphocyte and of recovery after UCBT K.A. et of graft-versus-host and recovery unrelated donor cord blood 2000; Google Scholar, P. et and after unrelated cord blood transplantation: a Marrow Transplant. 2000; PubMed Scopus Google Scholar, A. R. et of in children cord blood 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, cord blood transplantation in 2000; PubMed Scopus Google Scholar, T. Rocha V. et lymphocyte after related or unrelated cord blood transplantation in Eurocord J 2001; PubMed Scopus Google Scholar]. these studies may be as to of such as low of to and in of transplant and of posttransplant a analysis of lymphocyte recovery in 88 children who consecutively received UCBT in a pediatric transplant