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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
From Eurocord In order to compare the outcomes of unrelated umbilical cord blood
transplants (UCBTs) or bone marrow transplants, 541 children with acute leukemia (AL) transplanted with umbilical cord blood (n = 99), T-cell-depleted unrelated bone marrow transplants (T-UBMT) (n = 180), or nonmanipulated (UBMT) (n = 262), were analyzed in a
retrospective multicenter study. Comparisons were performed after
adjustment for patient, disease, and transplant variables. The
major difference between the 3 groups was the higher number in the UCBT
group of HLA mismatches (defined by serology for class I and molecular
typing for DRB1). The donor was HLA mismatched in 92% of UCBTs, in
18% of UBMTs, and in 43% of T-UBMTs (P < .001). Other
significant differences were observed in pretransplant disease characteristics, preparative regimens, graft-versus-host disease (GVHD)
prophylaxis, and number of cells infused. Nonadjusted estimates of
2-year survival and event-free survival rates were 49% and 43%,
respectively, in the UBMT group, 41% and 37% in the T-UBMT group, and
35% and 31% in the UCBT group. After adjustment, differences in outcomes appeared in the first 100 days after the transplantation. Compared with UBMT recipients, UCBT recipients had delayed
hematopoietic recovery (Hazard ratio [HR] = 0.37; 95% confidence
interval [95CI]: 0.27-0.52; P < .001), increased 100 day transplant-related mortality (HR = 2.13; 95CI: 1.20-3.76;
P < .01) and decreased acute graft-versus-host disease
(aGVHD) (HR = 0.50; 95CI: 0.34-0.73; P < .001). T-UBMT recipients had decreased aGVHD (HR = 0.25; 95CI: 0.17-0.36;
P < .0001) and increased risk of relapse (HR = 1.96;
95CI: 1.11-3.45; P = .02). After day 100 posttransplant,
the 3 groups achieved similar results in terms of relapse. Chronic GVHD
was decreased after T-UBMT (HR = 0.21; 95CI: 0.11-0.37;
P < .0001) and UCBT (HR = 0.24; 95CI: 0.01-0.66;
P = .002), and overall mortality was higher in T-UBMT
recipients (HR = 1.39; 95CI: 0.97-1.99; P < .07).
In conclusion, the use of UCBT, as a source of hematopoietic stem
cells, is a reasonable option for children with AL lacking an
acceptably matched unrelated marrow donor.
(Blood. 2001;97:2962-2971) Allogeneic hematopoietic stem cell transplants play
an important role in treating patients with high-risk acute leukemia
(AL). However, 70% of the children who might benefit from this therapy lack an HLA identical sibling donor. Despite the establishment of bone
marrow donor registries with more than 5 million unrelated volunteer
donors worldwide, finding a fully HLA-matched unrelated donor remains a
problem for many patients because of HLA polymorphism.1,2 Because of this, efforts have turned toward using HLA partially mismatched unrelated or related donors3-5 and other
sources of stem cells such as umbilical cord blood
cells6,7 or granulocyte-colony stimulating factor
(G-CSF)-mobilized T-cell-depleted peripheral blood hematopoietic stem
cells provided by related haploidentical donors.8
With the establishment of cord blood banks, more than 30 000 cord
blood units have been made available for
transplantation9-12 and facilitated more than 1200 unrelated umbilical cord blood transplants (UCBT) for children and
adults with either malignant or nonmalignant
diseases.7,13-17 In children with AL, cord blood has
potential advantages compared with bone marrow hematopoietic stem
cells, namely the rapid availability of cells and less stringent requirements for HLA identity between donor and recipient because of
the lower risk of acute and chronic graft-versus-host disease (GVHD).18 In addition, a previous Eurocord study has shown
that unrelated HLA-mismatched UCBT in children with AL gives results comparable to those reported with other sources of stem
cells.19
With better characterization of HLA types, improvements in GVHD
prophylaxis, and treatment of infectious diseases, results of
HLA-matched unrelated donor transplants have become comparable to
HLA-matched sibling transplants in children with AL.20
Also, T-cell-depleted HLA-matched and -mismatched
UBMT5,21-23 and T-cell-depleted haploidentical related
peripheral blood hematopoietic stem cell transplants in patients with
AL have also shown promising results.24 Consequently, the
number of allogeneic BMTs using alternative donors is increasing, as is
the difficulty in choosing the best donor for a specific patient. In
order to evaluate these different strategies, we compared the outcomes
of 99 children with AL receiving a UCBT to those of 442 children
receiving either a nonmanipulated UBMT (n = 262) or a T-UBMT
(n = 180).
Data collection and population
Bone marrow donor registries, cord blood banks, and
HLA typing
Donor-recipient histocompatibility was determined by serology for HLA-A and HLA-B antigens and by DNA typing for HLA-DRB1. Most HLA-DRB1 typing was performed by high molecular resolution allelic technique and only 15 (3%) donor-recipient pairs had low resolution molecular typing. All HLA data were reviewed and queries concerning patient and donor HLA typing were verified in transplant centers, bone marrow donor registries, and cord blood banks. Transplants were classified as HLA-mismatched with 1, 2, 3, or 4 differences if disparities were detected in HLA-A, HLA-B, or HLA-DRB1 antigens or alleles. Blanks at the same locus were considered matches only if the paired allele was the same. Outcomes Hematopoietic recovery.
Neutrophil and platelet recoveries were analyzed separately, and
defined by a neutrophil count of Graft-versus-host disease. Acute graft-versus-host disease (aGVHD) was diagnosed and graded at each transplant center according to Seattle criteria.25 All patients were considered at risk for developing aGVHD at day +1 after transplantation. The reason for this definition was that between day +1 to day +14 after transplantation, 20% of UBMT and 14% of UCBT recipients without neutrophil recovery had signs of aGVHD. Chronic GVHD (cGVHD) was defined according to standard criteria.26 Patients surviving for more than 100 days after transplantation with sustained donor engraftment were considered as evaluable for cGVHD. Relapse. Relapse was defined on the basis of morphologic evidence of leukemia in bone marrow, or other extramedullary organs. Early transplant-related mortality. Early transplant-related mortality (TRM) was defined as all causes of nonleukemic deaths occurring within 100 days after transplantation. Event-free survival. Event-free survival (EFS) was defined as time interval from transplantation to first event (either relapse or death in complete remission). Overall survival. Overall survival was defined as time between transplantation and death. Statistical analysis Analysis used January 1, 1999, as the reference date, that is, the day on which all centers locked data on patient outcomes.Patient-, disease-, and transplant-related variables of the 3 transplant groups were compared, using the Fisher exact test for categoric variables and the nonparametric Kruskal-Wallis test for continuous variables. Since the outcomes following transplantation were all right-censored
(neutrophil and platelet recoveries, acute and chronic GVHD, relapse,
TRM, survival, and EFS), time to each endpoint was estimated by the
Kaplan-Meier method. Cox models were used to evaluate the joint
influence of patient-, disease-, and transplant-related variables
(Table 1) on each endpoint, in each
transplant group, separately. To ensure the availability of all input
variables where and when prediction will be made, and owing to a
strategy of data reduction, all variables with high rate of missing
values (
Model selection used the following steps for each endpoint. The first
step was to fit models that contained each of the variables one at a
time (univariable models). Continuous variables were dichotomized
according to median values. For categoric variables, dummy variables
for all but one category were created, taking on the value 1 for
patients in that category and 0 otherwise. Hypotheses of proportional
hazards were checked using time-varying coefficients. Variables
considered were: recipient age (< or Statistical analysis used the SAS (Sas, Cary, NC) and S-Plus Software (MathSoft, Seattle, WA).
Patient, donor, and disease characteristics A total of 262 children with AL received UBMTs, 180 received T-UBMTs, and 99 received UCBTs. Table 1 and Table 2 show the main characteristics of the 541 enrolled children. Compared with UBMT or T-UBMT recipients, recipients of UCBTs were younger (P = .004), were more likely to have acute myeloblastic leukemia (AML) (P = .014), were previously treated for relapses of leukemia with autologous (n = 12) or allogeneic stem cell transplants (n = 2) (P = .0001), and tended to have early relapses on therapy before transplant (P = .08). Eighteen children (18%) receiving a UCBT and 52 (20%) receiving a UBMT were transplanted in advanced stages of leukemia (refractory, relapse, or partial response), whereas in the T-UBMT group, only 17 (9%) patients were in an advanced stage of the disease (P = .04). One hundred and twenty-five patients with acute lymphoblastic leukemia (ALL) received transplants in first and second complete remission (CR1 and CR2) using a UBMT, 107 using a T-UBMT, and 45 using a UCBT. Thirty-six patients with AML in CR1 and CR2 received a transplant using a UBMT, 26 using a T-UBMT, and 22 using a UCBT. Median time from diagnosis to transplantation was 15 months in the UCBT group compared with 22 months in the UBMT group (P = .03). Results of HLA typing are shown in Table 3. Mismatches were mostly observed for class I in UBMT and T-UBMT and for any of class I and class II HLA antigens in the UCBT group.
Transplant characteristics: preparative regimens, GVHD prophylaxis, supportive treatment, and graft composition Preparative regimens varied according to patient's age, disease status, and transplant center protocols (Table 2). Addition of an anti-T-cell antibody before transplantation was commonly given to patients receiving T-UBMTs or UCBTs (P = .0001). GVHD prophylaxis differed: most of the UBMT recipients (69%) received the combination of cyclosporine A (CsA) and methotrexate (MTX), 53% of the T-UBMT recipients received CsA alone, and 63% of UCBT recipients received CsA and corticosteroids. In the T-UBMT group, CAMPATH-1M22 was used for ex-vivo T-cell-depletion in 132 cases (73%). Supportive therapy, as well as prophylaxis and treatment of infections, varied among centers. Recombinant human granulocyte colony-stimulating factor (rHuG-CSF) or recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) were more frequently used early after UCBTs (P < .001). Finally and importantly, umbilical cord blood grafts contained one log fewer nucleated cells than bone marrow grafts (P < .001).Outcomes: univariate analysis (nonadjusted for patient, disease, and transplant differences) On January 1, 1999, the median follow-up was 29 months (range: 7-60 months); it was significantly shorter in the UCBT group (P < .001) since most of UCBTs (90%) were performed after January 1996.Table 4 lists probabilities of neutrophil
and platelets recovery, acute and chronic GVHD, early transplant
related mortality, relapse, and overall survival by transplant type not
adjusted for differences in factors that influence transplant outcome. It showed a significant delay of neutrophil and platelet recovery in
the UCBT group compared with the UBMT and the T-UBMT groups (P < .001). The incidence and severity of acute and
chronic GVHD are shown in Table 4. Table 4 shows a significant
reduction of aGVHD
We separately analyzed all the outcome variables on time scale, using day 100 posttransplantation as the cut-off, since the estimated relative effect of the UCBT group over the T-UBMT and UBMT groups was not proportional over time (P = .017) with decreased relative hazards after approximately day 100. We thus distinguished 2 types of outcomes, namely early outcomes within the first 100 days posttransplantation (neutrophil and platelet recoveries, aGVHD, early relapse, TRM), and long-term outcomes in survivors at day 100 posttransplantation (cGVHD, late relapse, overall survival, and EFS). Multivariable analysis Prognostic factors.
We first attempted to select the variables that could be associated
with each outcome separately in each transplant group. Table
6 reports the prognostic value of the
variables retained after a stepwise selection procedure, at the 10%
level, when jointly introduced into Cox models.
Early outcomes. Briefly, neutrophil and platelet recoveries were associated with cell dose in T-UBMTs and UCBTs and not in UBMTs. Relapse during the first 100 days was associated with the recipient's positive cytomegalovirus (CMV) serology, advanced leukemia at transplantation, and gender match in the UBMT group, whereas it was associated with younger patients, AML, and advanced stage of the disease in the UCBT group. We did not find any prognosis factor for relapse in the T-UBMT group. In the T-UBMT group, increased TRM at 100 days was associated with HLA incompatibility and sex match. We could not identify prognosis factors for TRM in the UCBT group. Long-term outcomes. The risk of relapse and death increased in all the groups of patients transplanted for leukemia in advanced stage of the disease. The risk of death increased in the T-UBMT group receiving an HLA-mismatched transplant but not in the other groups. Outcomes comparison (adjusted for prognostic factors) After selection of predictors for each endpoint in the 3 transplant groups, we used these predictors to adjust transplant group comparisons on outcomes. UBMTs defined the reference group, that is, with a baseline hazard ratio of 1.0.Early outcomes.
Although T-UBMT and UBMT groups did not
differ in terms of time to hematopoietic recovery and
treatment-related mortality, the main findings that emerged from these
adjusted comparisons were the poor results in the UCBT group regarding
these outcomes (Figure 2A). Indeed,
hematopoietic recoveries were delayed and less frequent, either in
terms of neutrophil or platelet recoveries (P = .00001,
each), and an increased TRM was observed
(P < .01). Conversely, the UCBT and T-UBMT
groups less frequently experienced grade II-IV acute GVHD. Finally,
whereas UBMT and UCBT groups experienced similar risks of early
relapse, there was a higher risk of relapse in the T-UBMT group
(P = .02) (Figure 2A).
Long-term outcomes. The UBMT group was unfavorable in terms of risk of cGVHD compared with the T-UBMT group (P = .0001) and the UCBT group (P = .002) (Figure 2B). By contrast, whereas the outcome of the 3 groups was comparable in terms of long-term relapse, mortality after day 100 was increased in the T-UBMT group (P = .07) and comparable in the UBMT and UCBT groups (Figure 2B). Of note is that the poor outcome of the T-UBMT group was influenced by the past occurrence within the first 100 days posttransplantation of the lack of engraftment (P = .055), early relapse (P < .0001), and grade II-IV aGVHD (P = .0006) (data not shown). These findings were slightly modified after stratifying on either EBMT centers or large centers, although the over-mortality in the T-depletion group after day 100 posttransplantation became statistically significant when stratifying on the EBMT centers (HR = 1.57, 95CI: 1.07-2.30; P = .02) (data not shown). In summary, the main differences in adjusted outcomes between the 3 transplant groups appeared in the first 100 days after the transplant. Indeed, delayed and failure of engraftment, and increased treatment-related mortality after UCBT must be compared with the higher risk of aGVHD after UBMT and to the higher risk of relapse after T-UBMT. In contrast, after day 100, the 3 transplant groups achieved similar results in terms of relapse, but cGVHD occurred more frequently after UBMT and death after T-UBMT.
This registry-based analysis included a large number of children receiving an allogeneic hematopoietic stem cell transplant for AL using an alternative donor. The objective of our study was to retrospectively compare the outcome of transplantations using unrelated bone marrow or cord blood as a source of hematopoietic stem cells in 541 children with AL. We compared outcomes after adjustment for patient-, disease-, and transplant-related factors based on separate multivariable prognostic analyses. We found several differences between unrelated BMT recipients and UCBT recipients. First, among the unrelated BMT recipients, we had to separately analyze nonmanipulated unrelated bone marrow transplants (UBMT) and T-cell-depleted UBMT. We thus compared 3 types of transplants. The first group of 262 patients received UBMTs; most of the donors were HLA matched for class I by serology and molecular typing for DRB1. As shown in the literature and in this study, this group experienced a high rate of acute and chronic GVHD and a low rate of relapse.23 The second group received T-UBMTs. Despite the fact that there were more class II mismatches, the patients in the second group experienced less acute and chronic GVHD and more rejections,21,22 more relapses,27 and delayed immune reconstitution.28,29 The group of UCBT patients had the highest number of HLA mismatches. These patients commonly experienced delayed hematologic reconstitution probably because they received one log less nucleated cells in the graft than the other groups. They also had less acute and chronic GVHD.18 Many pretransplant differences were observed among children receiving UBMTs, T-UBMTs, and UCBTs that probably influenced our ability to detect both advantages and disadvantages associated with each approach. The most important difference was related to HLA disparity since almost all UCBT patients had class I and class II HLA incompatibilities. However, the role of HLA mismatches was difficult to analyze because of the limitation of HLA typing methods which until recently did not take into consideration allelic variations and because most of the molecular HLA class I mismatches were not considered for the choice of donor recipient pairs. This has been changing recently as many centers are now using molecular techniques for both class I and class II typing.30-32 Since cord blood units were only recently available, UCBT patients had shorter follow-up than UBMT patients. Cord blood recipients were more likely to have adverse prognostic factors than the other transplant groups including early relapse before transplantation, shorter time interval from diagnosis to transplantation, and more patients receiving UCBT as a second transplant following relapse after a first autologous or allogeneic BMT. In order to take into account the potential measurable differences in patients according to center, we adjusted treatment comparison on baseline characteristics possibly related to the outcome and to the center. Although these differences were accounted for in the multivariable analyses, many other important baseline differences were observed among the 3 groups that were expected to modify the transplant outcome, including conditioning and GVHD prevention. Also, differences in supportive care and transplant center effect might have influenced our results. In a recent analysis of the EBMT group, center effect was an important factor influencing the outcome of HLA-identical bone marrow transplantation for AML in first complete remission.33 In addition, inequality in the type of patients contributed to the study by each center taken together with center-specific differences in coding GVHD may have contributed to some of the differences observed. Therefore, to incorporate potential difference in baseline hazard on either outcome between EBMT centers and others, as well as between large centers (that is, centers having reported at least 15 transplants, whatever the transplant group) and others, we finally stratified transplant group comparisons on these 2 variables, separately, without markedly modifying our results. The principal difference in adjusted outcomes observed was more transplant-related deaths in the UCBT group in the first 100 days. After day 100, relapse rates were nearly identical but cGVHD occurred more frequently in UBMT patients and more deaths occurred after T-UBMT. Nevertheless, the low number of exposed patients in surviving patients and the shorter follow-up should be considered, and further studies based on larger samples size are required for definitive conclusions. The major complication after UCBT was delayed neutrophil and platelet recovery. Others and we have shown that a cord blood nucleated cell dose above 0.37 × 108/kg was associated with increased probability of engraftment.7,16,17 In a previous report, patients with AL receiving a UBMT, a marrow cell dose above 3.65 × 108/kg had a better survival rate.34 In our study, patients who received more than 3.7 × 108 marrow nucleated cells infused per recipient's weight (one log higher than cord blood cells) engrafted more rapidly than patients receiving less. Our results confirm our previous recommendation that cord blood units should be selected on the basis of a number of nucleated cells > 0.37 × 108/kg recipient body weight after thawing.16 However, the minimum number of nucleated cells necessary for engraftment has not yet been established. The cause for delayed recovery after cord blood transplant might be due to the low number of cells infused or to other factors such as the immaturity of stem cells, which might need more cell divisions before differentiation to marrow progenitors, or to the lack of subpopulations facilitating engraftment.35 Whether current approaches being explored to speed hematopoietic recovery after cord blood transplantation, such as ex-vivo expansion, will result in decreased TRM is unknown.36 The incidence of grade II-IV aGVHD was lower after T-UBMT and intermediate with UCBT compared with UBMT. Since the majority of UCBT patients were mismatched, it was not possible to compare matched UBMT patients with matched UCBT patients; however, after adjustment for prognostic factors, aGVHD was reduced even in mismatched UCBT patients. The incidence of cGVHD was identical in both UCBT patients and T-UBMT patients, both being significantly lower than after UBMT. We showed also that the incidence of severe grade III-IV GVHD was reduced after UCBT and T-BMT. This confirms our previous observations that acute and chronic GVHD were significantly reduced when comparing HLA-identical sibling bone marrow and HLA-identical cord blood transplants.18 This study shows that the decreased incidence of acute and chronic GVHD after UCBT is still observed in the presence of major class I and class II HLA differences. This observation lends support to the hypothesis that umbilical cord blood differs from adult bone marrow in its alloreactive potential. The hypothesis that reduced GVHD results from fewer T cells infused is plausible since T-cell depletion of bone marrow transplants leads to a similarly lower GVHD risk. However, the number of T cells infused with umbilical cord blood transplants is on the order of 8 × 106/kg and it is known that GVHD can be induced by as few as 106 CD3 cells/kg and even fewer in HLA-mismatched situations.8 Since aGVHD results from activation, clonal expansion, and proliferation of donor-derived T lymphocytes that recognize alloantigens presented by either host or donor antigen-presenting cells, the lower GVHD risk after UCBT might be due to an impairment of these functions in umbilical cord blood cells. Therefore, identifying units with complete HLA identity does not seem to be an absolute prerequisite for a successful UCBT, as we did not find any correlation between the number of HLA mismatches and the outcome of UCBT. The number of HLA mismatches was an adverse prognostic factor for engraftment and survival after T-UBMT but not after UBMT. Because the interaction between lower risk of GVHD and higher risk of leukemic relapse is known, we expected a higher risk in the UCBT and T-UBMT groups than in the UBMT group. In the present study, we did not find any difference between the adjusted risk of relapse in the UBMT group and the UCBT group. The probability of early relapse was higher in the T-UBMT group but more follow-up and more patients in defined risk groups are necessary for a better comparison. In conclusion, we show that results were similar in the 3 groups of patients but the type of complications differed with more acute and chronic GVHD in the UBMT group, more relapses in the T-UBMT group, and more early deaths in the UCBT group. These findings show that both UBMT and UCBT represent alternatives for children with AL lacking a matched sibling donor. Developing the donor stem cell pool with bone marrow donors typed with high molecular resolution techniques to decrease the severity of GVHD1,2 and also increasing the number of cord blood units stored through international accredited cord blood banks should both result in an improved cure rate of children with AL given an unrelated hematopoietic stem cell transplant. At this stage, we recommend simultaneously searching bone marrow donor registries and cord blood banks. The final choice of stem cell source must take into account the degree of HLA identity, the availability of the donor, the urgency of the transplant, and the cell dose in the cord blood unit.
We would like to thank the Netcord banks: G. Koegler at Dusseldorf CBB; P. Rebulla at Milano CBB; S. Querol and J. Garcia at Barcelona CBB; S. Armitage and M. Contreras at London CBB; and JP Marolleau and M. Benbunan at Paris CBB. We also thank all bone marrow donors registries, and the data managers from all centers for their input in collecting data and answering our queries.
Submitted May 22, 2000; accepted February 5, 2001.
Supported by an EEC grant for Eurocord BIOMED II QLRT-1999-00380, by Etablissement Français des Greffes and PHRC 96, Ministry of Health, Association pour la Recherche contre le Cancer (ARC9085).
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Eliane Gluckman, Eurocord Registry
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1997;89:4226-4235
35.
Martin PJ, Akatsuka Y, Hahne M, Sale G.
Involvement of donor T-cell cytotoxic effector mechanisms in preventing allogeneic marrow rejection.
Blood.
1998;92:2177-2181 36. Koegler G, Nurnberger J, Fisher J, et al. Simultaneous cord blood transplantation of ex-vivo expanded together with nonexpanded cells for high risk leukemia. Bone Marrow Transplant. 1999;24:397-403[CrossRef][Medline] [Order article via Infotrieve].
Transplant centers
reporting unrelated bone marrow transplants and/or umbilical cord blood
transplants in children with acute leukemia are listed in the
following table.
© 2001 by The American Society of Hematology.
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  M. R. Verneris, C. G. Brunstein, J. Barker, M. L. MacMillan, T. DeFor, D. H. McKenna, M. J. Burke, B. R. Blazar, J. S. Miller, P. B. McGlave, et al. Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units Blood, November 5, 2009; 114(19): 4293 - 4299. [Abstract] [Full Text] [PDF]
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 K. KOBAYASHI, Y. MAEDA, Y. HARA, M. NISHIE-KATAOKA, H. NISHIMORI, H. SUGIYAMA, N. NAMBA, S. KUBONISHI, M. NIIYA, K. SHINAGAWA, et al. Clinical Outcomes of Unrelated Donor Umbilical Cord Blood Transplantation for 30 Adults with Hematological Malignancies Anticancer Res, May 1, 2009; 29(5): 1763 - 1770. [Abstract] [Full Text] [PDF]
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 E. Gluckman and V. Rocha Cord blood transplantation: state of the art Haematologica, April 1, 2009; 94(4): 451 - 454. [Full Text] [PDF]
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 G N Samuel, K A Strong, I Kerridge, C F C Jordens, R A Ankeny, and P J Shaw Establishing the role of pre-implantation genetic diagnosis with human leucocyte antigen typing: what place do "saviour siblings" have in paediatric transplantation? Arch. Dis. Child., April 1, 2009; 94(4): 317 - 320. [Abstract] [Full Text] [PDF]
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M. L. MacMillan, D. J. Weisdorf, C. G. Brunstein, Q. Cao, T. E. DeFor, M. R. Verneris, B. R. Blazar, and J. E. Wagner Acute graft-versus-host disease after unrelated donor umbilical cord blood transplantation: analysis of risk factors Blood, March 12, 2009; 113(11): 2410 - 2415. [Abstract] [Full Text] [PDF]
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Y. Atsuta, R. Suzuki, T. Nagamura-Inoue, S. Taniguchi, S. Takahashi, S. Kai, H. Sakamaki, Y. Kouzai, M. Kasai, T. Fukuda, et al. Disease-specific analyses of unrelated cord blood transplantation compared with unrelated bone marrow transplantation in adult patients with acute leukemia Blood, February 19, 2009; 113(8): 1631 - 1638. [Abstract] [Full Text] [PDF]
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E. Morra, G. Barosi, A. Bosi, F. Ferrara, F. Locatelli, M. Marchetti, G. Martinelli, C. Mecucci, M. Vignetti, and S. Tura Clinical management of primary non-acute promyelocytic leukemia acute myeloid leukemia: practice Guidelines by the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation Haematologica, January 1, 2009; 94(1): 102 - 112. [Abstract] [Full Text] [PDF]
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D. Lisini, M. Zecca, G. Giorgiani, D. Montagna, R. Cristantielli, M. Labirio, P. Grignani, C. Previdere, A. Di Cesare-Merlone, G. Amendola, et al. Donor/recipient mixed chimerism does not predict graft failure in children with {beta}-thalassemia given an allogeneic cord blood transplant from an HLA-identical sibling Haematologica, December 1, 2008; 93(12): 1859 - 1867. [Abstract] [Full Text] [PDF]
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J. Kurtzberg, V. K. Prasad, S. L. Carter, J. E. Wagner, L. A. Baxter-Lowe, D. Wall, N. Kapoor, E. C. Guinan, S. A. Feig, E. L. Wagner, 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, November 15, 2008; 112(10): 4318 - 4327. [Abstract] [Full Text] [PDF]
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V. K. Prasad, A. Mendizabal, S. H. Parikh, P. Szabolcs, T. A. Driscoll, K. Page, S. Lakshminarayanan, J. Allison, S. Wood, D. Semmel, et al. Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes Blood, October 1, 2008; 112(7): 2979 - 2989. [Abstract] [Full Text] [PDF]
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A. P. Iori, W. Arcese, F. Milano, E. Calabrese, G. F. Torelli, W. Barberi, M. G. Mascolo, L. De Felice, M. Screnci, B. Lucarelli, et al. Unrelated cord blood transplant in children with high-risk acute lymphoblastic leukemia: a long-term follow-up Haematologica, August 1, 2007; 92(8): 1051 - 1058. [Abstract] [Full Text] [PDF]
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H. Fujii, J. D. Trudeau, D. T. Teachey, J. D. Fish, S. A. Grupp, K. R. Schultz, and G. S. D. Reid In vivo control of acute lymphoblastic leukemia by immunostimulatory CpG oligonucleotides Blood, March 1, 2007; 109(5): 2008 - 2013. [Abstract] [Full Text] [PDF]
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 Section on Hematology/Oncology and Section on Alle Cord Blood Banking for Potential Future Transplantation Pediatrics, January 1, 2007; 119(1): 165 - 170. [Abstract] [Full Text] [PDF]
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 M. Eapen, P. Rubinstein, M.-J. Zhang, B. M. Camitta, C. Stevens, M. S. Cairo, S. M. Davies, J. J. Doyle, J. Kurtzberg, M. A. Pulsipher, 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., January 1, 2006; 24(1): 145 - 151. [Abstract] [Full Text] [PDF]
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K. K. Ballen New trends in umbilical cord blood transplantation Blood, May 15, 2005; 105(10): 3786 - 3792. [Abstract] [Full Text] [PDF]
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 T. R. Katsumoto, J. Duda, A. Kim, Z. Wardak, G. Dranoff, D. W. Clapp, and K. Shannon Granulocyte/macrophage colony-stimulating factor and accessory cells modulate radioprotection by purified hematopoietic cells J. Exp. Med., March 21, 2005; 201(6): 853 - 858. [Abstract] [Full Text] [PDF]
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J. N. Barker, D. J. Weisdorf, T. E. DeFor, B. R. Blazar, P. B. McGlave, J. S. Miller, C. M. Verfaillie, and J. E. Wagner Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy Blood, February 1, 2005; 105(3): 1343 - 1347. [Abstract] [Full Text] [PDF]
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A. Hidalgo and P. S. Frenette Enforced fucosylation of neonatal CD34+ cells generates selectin ligands that enhance the initial interactions with microvessels but not homing to bone marrow Blood, January 15, 2005; 105(2): 567 - 575. [Abstract] [Full Text] [PDF]
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F. Locatelli, P. Nollke, M. Zecca, E. Korthof, E. Lanino, C. Peters, A. Pession, H. Kabisch, C. Uderzo, C. S. Bonfim, et al. Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial Blood, January 1, 2005; 105(1): 410 - 419. [Abstract] [Full Text] [PDF]
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S. Takahashi, T. Iseki, J. Ooi, A. Tomonari, K. Takasugi, Y. Shimohakamada, T. Yamada, K. Uchimaru, A. Tojo, N. Shirafuji, et al. Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies Blood, December 1, 2004; 104(12): 3813 - 3820. [Abstract] [Full Text] [PDF]
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 M. J. Laughlin, M. Eapen, P. Rubinstein, J. E. Wagner, M.-J. Zhang, R. E. Champlin, C. Stevens, J. N. Barker, R. P. Gale, H. M. Lazarus, et al. Outcomes after Transplantation of Cord Blood or Bone Marrow from Unrelated Donors in Adults with Leukemia N. Engl. J. Med., November 25, 2004; 351(22): 2265 - 2275. [Abstract] [Full Text] [PDF]
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V. Rocha, M. Labopin, G. Sanz, W. Arcese, R. Schwerdtfeger, A. Bosi, N. Jacobsen, T. Ruutu, M. de Lima, J. Finke, et al. Transplants of Umbilical-Cord Blood or Bone Marrow from Unrelated Donors in Adults with Acute Leukemia N. Engl. J. Med., November 25, 2004; 351(22): 2276 - 2285. [Abstract] [Full Text] [PDF]
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M. A. Sanz Cord-Blood Transplantation in Patients with Leukemia -- A Real Alternative for Adults N. Engl. J. Med., November 25, 2004; 351(22): 2328 - 2330. [Full Text] [PDF]
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L. Xia, J. M. McDaniel, T. Yago, A. Doeden, and R. P. McEver Surface fucosylation of human cord blood cells augments binding to P-selectin and E-selectin and enhances engraftment in bone marrow Blood, November 15, 2004; 104(10): 3091 - 3096. [Abstract] [Full Text] [PDF]
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N. Flomenberg, L. A. Baxter-Lowe, D. Confer, M. Fernandez-Vina, A. Filipovich, M. Horowitz, C. Hurley, C. Kollman, C. Anasetti, H. Noreen, et al. Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome Blood, October 1, 2004; 104(7): 1923 - 1930. [Abstract] [Full Text] [PDF]
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G. Fujisaki, M. Kami, Y. Kishi, S. L. Staba, and J. Kurtzberg Cord-Blood Transplants from Unrelated Donors in Hurler's Syndrome N. Engl. J. Med., July 29, 2004; 351(5): 506 - 507. [Full Text] [PDF]
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 S. Miyakoshi, K. Yuji, M. Kami, E. Kusumi, Y. Kishi, K. Kobayashi, N. Murashige, T. Hamaki, S.-W. Kim, J.-i. Ueyama, et al. Successful Engraftment After Reduced-Intensity Umbilical Cord Blood Transplantation for Adult Patients with Advanced Hematological Diseases Clin. Cancer Res., June 1, 2004; 10(11): 3586 - 3592. [Abstract] [Full Text] [PDF]
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D. Montagna, F. Locatelli, A. Moretta, D. Lisini, C. Previdere, P. Grignani, P. DeStefano, G. Giorgiani, E. Montini, S. Pagani, et al. T lymphocytes of recipient origin may contribute to the recovery of specific immune response toward viruses and fungi in children undergoing cord blood transplantation Blood, June 1, 2004; 103(11): 4322 - 4329. [Abstract] [Full Text] [PDF]
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 H. Jiang, C. Van de Ven, P. Satwani, L. V. Baxi, and M. S. Cairo Differential Gene Expression Patterns by Oligonucleotide Microarray of Basal versus Lipopolysaccharide-Activated Monocytes from Cord Blood versus Adult Peripheral Blood J. Immunol., May 15, 2004; 172(10): 5870 - 5879. [Abstract] [Full Text] [PDF]
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J. Ooi, T. Iseki, S. Takahashi, A. Tomonari, K. Takasugi, Y. Shimohakamada, T. Yamada, K. Ishii, N. Ohno, F. Nagamura, et al. Unrelated cord blood transplantation for adult patients with de novo acute myeloid leukemia Blood, January 15, 2004; 103(2): 489 - 491. [Abstract] [Full Text] [PDF]
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 N. J. Chao, S. G. Emerson, and K. I. Weinberg Stem Cell Transplantation (Cord Blood Transplants) Hematology, January 1, 2004; 2004(1): 354 - 371. [Abstract] [Full Text] [PDF]
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G. Michel, V. Rocha, S. Chevret, W. Arcese, K.-W. Chan, A. Filipovich, T. A. Takahashi, M. Vowels, J. Ortega, P. Bordigoni, et al. Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis Blood, December 15, 2003; 102(13): 4290 - 4297. [Abstract] [Full Text] [PDF]
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S. Cookson and D. Reen IL-15 drives neonatal T cells to acquire CD56 and become activated effector cells Blood, September 15, 2003; 102(6): 2195 - 2197. [Abstract] [Full Text] [PDF]
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J. N. Barker, D. J. Weisdorf, T. E. DeFor, B. R. Blazar, J. S. Miller, and J. E. Wagner Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning Blood, September 1, 2003; 102(5): 1915 - 1919. [Abstract] [Full Text] [PDF]
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F. Frassoni, M. Podesta, R. Maccario, G. Giorgiani, G. Rossi, M. Zecca, A. Bacigalupo, G. Piaggio, and F. Locatelli Cord blood transplantation provides better reconstitution of hematopoietic reservoir compared with bone marrow transplantation Blood, August 1, 2003; 102(3): 1138 - 1141. [Abstract] [Full Text] [PDF]
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S. S. Grewal, J. N. Barker, S. M. Davies, and J. E. Wagner Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood? Blood, June 1, 2003; 101(11): 4233 - 4244. [Full Text] [PDF]
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W. Reed, R. Smith, F. Dekovic, J. Y. Lee, J. D. Saba, E. Trachtenberg, J. Epstein, S. Haaz, M. C. Walters, and B. H. Lubin Comprehensive banking of sibling donor cord blood for children with malignant and nonmalignant disease Blood, January 1, 2003; 101(1): 351 - 357. [Abstract] [Full Text] [PDF]
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J. E. Wagner, J. N. Barker, T. E. DeFor, K. S. Baker, B. R. Blazar, C. Eide, A. Goldman, J. Kersey, W. Krivit, M. L. MacMillan, et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival Blood, August 13, 2002; 100(5): 1611 - 1618. [Abstract] [Full Text] [PDF]
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A. E. Woolfrey, C. Anasetti, B. Storer, K. Doney, L. A. Milner, E. L. Sievers, P. Carpenter, P. Martin, E. Petersdorf, F. R. Appelbaum, et al. Factors associated with outcome after unrelated marrow transplantation for treatment of acute lymphoblastic leukemia in children Blood, March 15, 2002; 99(6): 2002 - 2008. [Abstract] [Full Text] [PDF]
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W. R. Drobyski, J. Klein, N. Flomenberg, D. Pietryga, D. H. Vesole, D. A. Margolis, and C. A. Keever-Taylor Superior survival associated with transplantation of matched unrelated versus one-antigen-mismatched unrelated or highly human leukocyte antigen- disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishing a treatment algorithm for recipients of alternative donor grafts Blood, February 1, 2002; 99(3): 806 - 814. [Abstract] [Full Text] [PDF]
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D. Hoelzer, N. Gokbuget, O. Ottmann, C.-H. Pui, M. V. Relling, F. R. Appelbaum, J. J.M. van Dongen, and T. Szczepanski Acute Lymphoblastic Leukemia Hematology, January 1, 2002; 2002(1): 162 - 192. [Abstract] [Full Text] [PDF]
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 H. Igarashi, T. Kouro, T. Yokota, P. C. Comp, and P. W. Kincade Age and stage dependency of estrogen receptor expression by lymphocyte precursors PNAS, December 18, 2001; 98(26): 15131 - 15136. [Abstract] [Full Text] [PDF]
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G. F. Sanz, S. Saavedra, D. Planelles, L. Senent, J. Cervera, E. Barragan, C. Jimenez, L. Larrea, G. Martin, J. Martinez, et al. Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies Blood, October 15, 2001; 98(8): 2332 - 2338. [Abstract] [Full Text] [PDF]
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E. Gluckman Hematopoietic Stem-Cell Transplants Using Umbilical-Cord Blood N. Engl. J. Med., June 14, 2001; 344(24): 1860 - 1861. [Full Text] [PDF]
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| Copyright © 2001 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
Cord Blood Transplant Group (CBTG) and
Biostatistics Department, Saint Louis Hospital AP-HP, University of
Paris 7, France; Hospital for Sick Children, Bristol, United Kingdom;
Fred Hutchinson Cancer Research Center, Seattle, WA; Children's
Hospital Medical Center, Cincinnati, OH; Clinica Pediatrica, IRCCS
Policlinico San Matteo, Pavia, Italy; St Anna Kinderspital, Vienna,
Austria; Huddinge University Hospital, Huddinge, Sweden; Hospital La
Timone, Marseille, France; University La Sapienza, Rome, Italy;
Institute G. Gaslini, Genoa, Italy; Royal Children's Hospital,
Melbourne, Australia; Ospedale Regina Margherita, Turin, Italy; MD
Anderson Cancer Center, Houston, TX; Tokai University School of
Medicine, Isehara, Japan; Hospital Infantil Vall d'Hebron, Barcelona,
Spain; Sydney Children's Hospital, Sydney, Australia; University
Hospital Eppendorf, Hamburg, Germany; Hospital Debrousse, Lyon, France;
Anthony Nolan Bone Marrow Trust Registry, London, United Kingdom;
National Blood Service, Bristol, United Kingdom; Duesseldorf Cord Blood
Bank, Duesseldorf, Germany; Milano Cord Blood Bank, Milano, Italy; New
York Cord Blood Bank, New York, NY.
Top
Abstract
Introduction
0.5 × 109/L for
3 consecutive days and a nontransfused platelet count of 
