Bone Marrow Transplantation (2015), 1–3 © 2015 Macmillan Publishers Limited All rights reserved 0268-3369/15 www.nature.com/bmt
LETTER TO THE EDITOR
Cord blood unit factors influencing transplant outcomes from the Asian multiethnic Singapore Cord Blood Bank Bone Marrow Transplantation advance online publication, 8 June 2015; doi:10.1038/bmt.2015.134
Cord blood transplants (CBTs) require less stringent matching for HLA, extending hematopoietic stem cell transplant to patients from ethnic minorities who are less likely to find an unrelated adult donor through registries. However, delayed engraftment and graft failure remain higher in CBT compared with transplants using other stem cell sources. The ability to predict the likelihood of successful engraftment of cord blood (CB) units based on information provided by CB banks is important for transplant success. The Singapore Cord Blood Bank (SCBB) is a NetCordFACT-accredited center that has been operating since 2005 and has provided over 200 CB units for transplant globally. CB units come from a multiethnic donor database, which provides an opportunity to evaluate transplant outcomes in a predominantly non-Caucasian population. There is also no prior study evaluating the impact of donor–recipient race-matching on GvHD in a South Asian population. Hence, we undertook an analysis to determine the graft characteristics that affect engraftment and risk of GvHD in a group of patients who received CB grafts from the SCBB. We retrospectively analyzed data from the SCBB for the first CB units distributed for transplant in 100 patients with ALL (30%), AML (45%), CML (17%) or myelodysplastic syndrome (MDS, 8%) between March 2008 and June 2013. The types of transplant included single (n = 53) and double (n = 47) CBT, with the majority receiving myeloablative conditioning regimens (73%). Most recipients in this study were over 18 years of age (65%). The ethnic distribution of the recipients was 49 Chinese, 13 Malay, 4 Indian, 21 Caucasian and 16 other or mixed ethnicity. In double CBT, donor–recipient HLA disparity was assigned on the basis of the dominant unit in double CB grafts. Most recipients (n = 82) received grafts matched at 5/6 or 6/6 HLA loci (HLA-A, HLA-B at intermediate resolution and HLA-DRB1 at high-resolution typing), whereas 18 received grafts matched at 4/6 loci. Patients gave informed consent for data entry into the SCBB registry database and for its use for analysis in accordance with the Declaration of Helsinki. The end points included: (1) neutrophil recovery, defined as absolute neutrophil count ⩾ 0.5 × 109/L for three consecutive days. Graft failure was defined as the lack of sustained neutrophil recovery, autologous recovery or repeat transplant. (2) Acute and chronic GvHD, diagnosed according to established criteria.1,2 The covariates considered were age at transplant ⩽ 18 years vs 418 years), diagnosis (AML/ALL vs CML/MDS), conditioning regimen (nonmyeloablative vs myeloablative), donor–recipient race (matched vs mismatched if either donor has a different racial background from recipient), cryopreserved total nucleated cell (TNC) and CD34+ cell counts of the single unit or engrafting unit in double CBT, HLA disparity (0–1 mismatch vs 2 mismatch) and transplant type (single CBT vs double CBT). HLA disparity and cell dose were maintained in the model, whereas other variables were selected in a backward stepwise manner with a variable retention criterion of P o 0.20. The median follow-up of surviving patients was 30 months (3–70 months). Eight patients had graft failure and one unit
dominated in all engrafting patients. The median cryopreserved TNC dose was 3.65 × 107/kg (range 1.40 × 107 to 14.8 × 107/kg) in single CBT and 2.70 × 107/kg (range 1.24 × 107 to 9.0 × 107/kg) in the engrafting unit of double CBT (P = NS). The corresponding CD34+ cell dose was 1.80 × 105/kg (range 0.71 × 105 to 6.5 × 105/kg) in single CBT and 1.49 × 105/kg (range 0.69 × 105 to 7 × 105/kg) in the engrafting unit of double CBT (P = NS). Median time to neutrophil recovery was 25 days. Significant predictors for neutrophil recovery in univariate analysis include CD34+ cell count 42 × 105/kg and engrafting unit HLA-A, -B, -DRB1 allele match ⩾ 5/6 to the recipient (Table 1). In multivariable Cox regression analysis, cryopreserved CD34+ cell dose 42 × 105/kg was associated with faster neutrophil recovery (hazard ratio (HR) 1.89, confidence interval (CI) 1.05–3.40, P = 0.33), whereas engrafting unit HLA-match no longer influenced neutrophil recovery rate (P = 0.073). At a higher CD34+ count 42 × 105/kg relative to ⩽ 2 × 105/kg, the estimated median neutrophil recovery was significantly faster at 22 days vs 30 days. In subgroup analysis, a CD34+ cell dose of the engrafting unit in double CBT above a threshold of 2 × 105/kg led to faster engraftment (HR 2.70, CI 1.13–6.39, P = 0.025), whereas the threshold CD34+ cell dose in single CBT was 2.4 × 105/kg (HR 2.40, CI 1.01–5.46, P = 0.046). Table 1.
Cox regression analyses of factors associated with neutrophil engraftment N1/N2 (%)
HR (95% CI)
P-value
Disease type AML and ALL CML and MDS
66.0 58.9
1.00 0.81 (0.46–1.41)
0.445
TNC (107/ kg) o2.5 2.5–5 45
65.0 70.3 45.5
1.00 1.58 (0.89–2.81) 0.88 (0.42–1.87)
0.119 0.749
CD34+ cells (105/ kg) o2 ⩾2
54.8 75.0
1.00 2.17 (1.02–4.62)
0.044
Conditioning regimen Non-myeloablative Myeloablative
66.7 55.6
1.00 0.80 (0.28–2.25)
0.667
HLA 0–1 mismatch 2 mismatch
57.8 86.0
1.00 2.33 (1.11–4.92)
0.026
Transplant type Single Double
65.8 63.3
1.00 0.83 (0.51–1.35)
0.242
Donor–recipient race Matched Mismatched
72.0 60.5
1.00 0.88 (0.53–1.47)
0.633
Risk factor
Abbreviations: CI = confidence interval; HR = hazard ratio; N1/N2 = number of patients with neutrophil engraftment at 28 days over total number of patients; MDS = myelodysplastic syndrome; TNC = total nucleated cell.
Letter to the Editor
2 Table 2.
Logistic regression analyses of factors potentially associated with acute and chronic GvHD N
Grade II–IV acute GvHD OR (95% CI)
P-value
N
Chronic GvHD OR (95% CI)
P-value
Donor–recipient race Matched Mismatched
23.1 27.5
1.00 1.23 (0.25–6.10)
0.797
23.0 22.5
1.00 0.97 (0.22–4.29)
0.966
TNC (107/ kg) o2.5 2.5–5 45
23.5 24.2 33.3
1.00 1.06 (0.21–5.29) 1.74 (0.38–7.87)
0.946 0.474
17.6 27.8 22.2
1.00 1.79 (0.36–9.05) 1.33 (0.25–7.08)
0.479 0.736
CD34+ cells (105/ kg) o2 ⩾2
24.1 30.4
1.00 1.42 (0.43–5.12)
0.539
20.7 26.1
1.00 1.35 (0.37–4.93)
0.647
Conditioning Myeloablative Non-Myeloablative
30.8 25.6
1.00 0.93 (0.20–4.39)
0.932
15.4 25.6
1.00 2.04 (0.18–22.6)
0.562
HLA 0–1 mismatch 2 mismatch
15.6 30.0
1.00 2.31 (0.44–12.1)
0.386
18.8 20.0
1.07 (0.17–6.79)
0.947
Transplant type Single Double
27.2 25.0
1.00 0.83 (0.21–3.26)
0.785
18.8 30.0
1.00 1.63 (0.39–6.81)
0.499
Factor
Abbreviations: CI = confidence interval; GvHD = graft-versus-host-disease; N = percentage of patients with acute or chronic GvHD; OR = odds ratio; TNC = total nucleated cell.
The cumulative incidence of grade II–IV GvHD was 26.0% (CI 14.0–39.0%), whereas that of chronic GvHD was 22.6% (CI 11.0–34.3%). Univariate logistic regression analysis revealed no relationship between conditioning intensity, donor–recipient race match, cell dose (TNC/CD34+), HLA disparity or transplant type (double vs single) with acute or chronic GvHD risk (Table 2). There was a trend toward a lower risk of acute grade II–IV GvHD in patients receiving grafts with 0–1 HLA mismatched units compared with 2 mismatches, but it did not reach significance. In multivariate analysis, cell dose (TNC, CD34+) and HLA disparity were both not associated with grade II–IV acute or chronic GvHD risk. In this study, cryopreserved CD34+ cell dose of the single CB unit or engrafting unit in double CBT were independent predictors of neutrophil recovery rate. Although previous studies in single CBT demonstrate favorable associations between both cryopreserved and infused CD34+ cell dose and engraftment rate,3,4 the importance of CD34+ cell dose in double CBT is less clearly defined.5–7 Furthermore, most data in double CBT are based on infused cell doses, with only one study showing favorable engraftment with higher cryopreserved CD34+ cell dose of the engrafted unit.7 Currently, CD34+ cell content is not used to assist in CB unit selection at many transplant centers because measurements are not standardized. However, several recent studies show that post-thaw CD34+ cell measurements are closely correlated to cryopreserved values provided by different banks,7,8 which suggest that CD34+ measurements may not be significantly different despite different enumeration methods. On the other hand, we found no influence of higher cryopreserved TNC doses on the rate of neutrophil engraftment, possibly owing to the relatively high TNC dose of the CB units in our series. Another reason may be the wide variability of CD34+ cells (×105) to TNC (×107) ratio (0.62 ± 0.89 (s.d.)) among CB units supplied for transplant from the SCBB, which suggests that TNC content may not be a good predictor of graft hematopoietic reconstitution potential. Bone Marrow Transplantation (2015), 1 – 3
Our study in a predominantly non-Caucasian population found no significant associations of recipient race or donor–recipient racial match on outcomes in both single and double CBT. Although some studies identified higher GvHD risk in ethnic minorities,9,10 others have not identified any effect.11 Differences in outcomes between races may be contributed by more significant minor histocompatibility antigen disparity in minorities, lower socio-economic status, or the inability to find a well-matched appropriately-sized cord unit for transplant.10,12 Using our local CB bank, a majority (82%) could identify ⩾ 5/6 HLA-matched grafts, and recipients of different racial backgrounds received grafts that were similar in the extent of HLA matching. There is no data at present to suggest that donor race should be included as a factor in CB unit selection. Limitations of the current study are the small sample size, retrospective setting and heterogeneity of conditioning regimens and transplant procedures. Importantly, we lacked information regarding relapse or disease status at transplant, which limits the validity of the multivariate analysis for transplant outcomes. Race was reported by the transplant center and may not be reflective of true genetic race. In summary, we have demonstrated the importance of cryopreserved CD34+ cell dose in engraftment outcomes after unrelated single and double CBT. CD34+ cell content of CB units reported by cord blood banks may be potentially a more relevant cellular content to optimize outcomes. CONFLICT OF INTEREST The authors declare no conflict of interest.
S-Y Ong1, C Phipps1, P Chu2, A Prasath2, AYL Ho1, SJ Sobak2 and W Hwang1,2 1 Department of Haematology, Singapore General Hospital, Singapore and 2 Singapore Cord Blood bank, Singapore E-mail: [email protected] © 2015 Macmillan Publishers Limited
Letter to the Editor
3
REFERENCES 1 Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956. 2 Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Henslee-Downey PJ et al. IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol 1997; 97: 855–864. 3 Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C 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 2002; 100: 1611–1618. 4 Barker JN, Byam CE, Kernan NA, Lee SS, Hawke RM, Doshi KA et al. Availability of cord blood extends allogeneic hematopoietic stem cell transplant access to racial and ethnic minorities. Biol Blood Marrow Transplant 2010; 16: 1541–1548. 5 Avery S, Shi W, Lubin M, Gonzales AM, Heller G, Castro-Malaspina H et al. Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts. Blood 2011; 117: 3277–3285. 6 Rocha V, Crotta A, Ruggeri A, Purtill D, Boudjedir K, Herr AL et al. Double cord blood transplantation: Extending the use of unrelated umbilical cord blood cells
© 2015 Macmillan Publishers Limited
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for patients with hematological diseases. Best Pract Res Clin Haematol 2010; 23: 223–229. Purtill D, Smith K, Devlin S, Meagher R, Tonon J, Lubin M et al. Dominant unit CD34+ cell dose predicts engraftment after double-unit cord blood transplantation and is influenced by cord blood bank practice. Blood 2014; 124: 2905–2912. Kudo Y, Minegishi M, Seki O, Takahashi H, Suzuki A, Narita A et al. Quality assessment of umbilical cord blood units at the time of transplantation. Int J Hematol 2011; 93: 645–651. Oh H, Loberiza FR Jr, Zhang MJ, Ringden O, Akiyama H, Asai T et al. Comparison of graft-versus-host-disease and survival after HLA-identical sibling bone marrow transplantation in ethnic populations. Blood 2005; 105: 1408–1416. Ballen KK, Klein JP, Pedersen TL, Bhatla D, Duerst R, Kurtzberg J et al. Relationship of race/ethnicity and survival after single umbilical cord blood transplantation for adults and children with leukemia and myelodysplastic syndromes. Biol Blood Marrow Transplant 2012; 18: 903–912. Ustun C, Bachanova V, Shanley R, MacMillan ML, Majhail NS, Arora M et al. Importance of donor ethnicity/race matching in unrelated adult and cord blood allogeneic hematopoietic cell transplant. Leuk lymphoma 2014; 55: 358–364. Spierings E, Hendriks M, Absi L, Canossi A, Chhaya S, Crowley J et al. Phenotype frequencies of autosomal minor histocompatibility antigens display significant differences among populations. PLoS Genet 2007; 3: e103.
Bone Marrow Transplantation (2015), 1 – 3
LETTER TO THE EDITOR
Cord blood unit factors influencing transplant outcomes from the Asian multiethnic Singapore Cord Blood Bank Bone Marrow Transplantation advance online publication, 8 June 2015; doi:10.1038/bmt.2015.134
Cord blood transplants (CBTs) require less stringent matching for HLA, extending hematopoietic stem cell transplant to patients from ethnic minorities who are less likely to find an unrelated adult donor through registries. However, delayed engraftment and graft failure remain higher in CBT compared with transplants using other stem cell sources. The ability to predict the likelihood of successful engraftment of cord blood (CB) units based on information provided by CB banks is important for transplant success. The Singapore Cord Blood Bank (SCBB) is a NetCordFACT-accredited center that has been operating since 2005 and has provided over 200 CB units for transplant globally. CB units come from a multiethnic donor database, which provides an opportunity to evaluate transplant outcomes in a predominantly non-Caucasian population. There is also no prior study evaluating the impact of donor–recipient race-matching on GvHD in a South Asian population. Hence, we undertook an analysis to determine the graft characteristics that affect engraftment and risk of GvHD in a group of patients who received CB grafts from the SCBB. We retrospectively analyzed data from the SCBB for the first CB units distributed for transplant in 100 patients with ALL (30%), AML (45%), CML (17%) or myelodysplastic syndrome (MDS, 8%) between March 2008 and June 2013. The types of transplant included single (n = 53) and double (n = 47) CBT, with the majority receiving myeloablative conditioning regimens (73%). Most recipients in this study were over 18 years of age (65%). The ethnic distribution of the recipients was 49 Chinese, 13 Malay, 4 Indian, 21 Caucasian and 16 other or mixed ethnicity. In double CBT, donor–recipient HLA disparity was assigned on the basis of the dominant unit in double CB grafts. Most recipients (n = 82) received grafts matched at 5/6 or 6/6 HLA loci (HLA-A, HLA-B at intermediate resolution and HLA-DRB1 at high-resolution typing), whereas 18 received grafts matched at 4/6 loci. Patients gave informed consent for data entry into the SCBB registry database and for its use for analysis in accordance with the Declaration of Helsinki. The end points included: (1) neutrophil recovery, defined as absolute neutrophil count ⩾ 0.5 × 109/L for three consecutive days. Graft failure was defined as the lack of sustained neutrophil recovery, autologous recovery or repeat transplant. (2) Acute and chronic GvHD, diagnosed according to established criteria.1,2 The covariates considered were age at transplant ⩽ 18 years vs 418 years), diagnosis (AML/ALL vs CML/MDS), conditioning regimen (nonmyeloablative vs myeloablative), donor–recipient race (matched vs mismatched if either donor has a different racial background from recipient), cryopreserved total nucleated cell (TNC) and CD34+ cell counts of the single unit or engrafting unit in double CBT, HLA disparity (0–1 mismatch vs 2 mismatch) and transplant type (single CBT vs double CBT). HLA disparity and cell dose were maintained in the model, whereas other variables were selected in a backward stepwise manner with a variable retention criterion of P o 0.20. The median follow-up of surviving patients was 30 months (3–70 months). Eight patients had graft failure and one unit
dominated in all engrafting patients. The median cryopreserved TNC dose was 3.65 × 107/kg (range 1.40 × 107 to 14.8 × 107/kg) in single CBT and 2.70 × 107/kg (range 1.24 × 107 to 9.0 × 107/kg) in the engrafting unit of double CBT (P = NS). The corresponding CD34+ cell dose was 1.80 × 105/kg (range 0.71 × 105 to 6.5 × 105/kg) in single CBT and 1.49 × 105/kg (range 0.69 × 105 to 7 × 105/kg) in the engrafting unit of double CBT (P = NS). Median time to neutrophil recovery was 25 days. Significant predictors for neutrophil recovery in univariate analysis include CD34+ cell count 42 × 105/kg and engrafting unit HLA-A, -B, -DRB1 allele match ⩾ 5/6 to the recipient (Table 1). In multivariable Cox regression analysis, cryopreserved CD34+ cell dose 42 × 105/kg was associated with faster neutrophil recovery (hazard ratio (HR) 1.89, confidence interval (CI) 1.05–3.40, P = 0.33), whereas engrafting unit HLA-match no longer influenced neutrophil recovery rate (P = 0.073). At a higher CD34+ count 42 × 105/kg relative to ⩽ 2 × 105/kg, the estimated median neutrophil recovery was significantly faster at 22 days vs 30 days. In subgroup analysis, a CD34+ cell dose of the engrafting unit in double CBT above a threshold of 2 × 105/kg led to faster engraftment (HR 2.70, CI 1.13–6.39, P = 0.025), whereas the threshold CD34+ cell dose in single CBT was 2.4 × 105/kg (HR 2.40, CI 1.01–5.46, P = 0.046). Table 1.
Cox regression analyses of factors associated with neutrophil engraftment N1/N2 (%)
HR (95% CI)
P-value
Disease type AML and ALL CML and MDS
66.0 58.9
1.00 0.81 (0.46–1.41)
0.445
TNC (107/ kg) o2.5 2.5–5 45
65.0 70.3 45.5
1.00 1.58 (0.89–2.81) 0.88 (0.42–1.87)
0.119 0.749
CD34+ cells (105/ kg) o2 ⩾2
54.8 75.0
1.00 2.17 (1.02–4.62)
0.044
Conditioning regimen Non-myeloablative Myeloablative
66.7 55.6
1.00 0.80 (0.28–2.25)
0.667
HLA 0–1 mismatch 2 mismatch
57.8 86.0
1.00 2.33 (1.11–4.92)
0.026
Transplant type Single Double
65.8 63.3
1.00 0.83 (0.51–1.35)
0.242
Donor–recipient race Matched Mismatched
72.0 60.5
1.00 0.88 (0.53–1.47)
0.633
Risk factor
Abbreviations: CI = confidence interval; HR = hazard ratio; N1/N2 = number of patients with neutrophil engraftment at 28 days over total number of patients; MDS = myelodysplastic syndrome; TNC = total nucleated cell.
Letter to the Editor
2 Table 2.
Logistic regression analyses of factors potentially associated with acute and chronic GvHD N
Grade II–IV acute GvHD OR (95% CI)
P-value
N
Chronic GvHD OR (95% CI)
P-value
Donor–recipient race Matched Mismatched
23.1 27.5
1.00 1.23 (0.25–6.10)
0.797
23.0 22.5
1.00 0.97 (0.22–4.29)
0.966
TNC (107/ kg) o2.5 2.5–5 45
23.5 24.2 33.3
1.00 1.06 (0.21–5.29) 1.74 (0.38–7.87)
0.946 0.474
17.6 27.8 22.2
1.00 1.79 (0.36–9.05) 1.33 (0.25–7.08)
0.479 0.736
CD34+ cells (105/ kg) o2 ⩾2
24.1 30.4
1.00 1.42 (0.43–5.12)
0.539
20.7 26.1
1.00 1.35 (0.37–4.93)
0.647
Conditioning Myeloablative Non-Myeloablative
30.8 25.6
1.00 0.93 (0.20–4.39)
0.932
15.4 25.6
1.00 2.04 (0.18–22.6)
0.562
HLA 0–1 mismatch 2 mismatch
15.6 30.0
1.00 2.31 (0.44–12.1)
0.386
18.8 20.0
1.07 (0.17–6.79)
0.947
Transplant type Single Double
27.2 25.0
1.00 0.83 (0.21–3.26)
0.785
18.8 30.0
1.00 1.63 (0.39–6.81)
0.499
Factor
Abbreviations: CI = confidence interval; GvHD = graft-versus-host-disease; N = percentage of patients with acute or chronic GvHD; OR = odds ratio; TNC = total nucleated cell.
The cumulative incidence of grade II–IV GvHD was 26.0% (CI 14.0–39.0%), whereas that of chronic GvHD was 22.6% (CI 11.0–34.3%). Univariate logistic regression analysis revealed no relationship between conditioning intensity, donor–recipient race match, cell dose (TNC/CD34+), HLA disparity or transplant type (double vs single) with acute or chronic GvHD risk (Table 2). There was a trend toward a lower risk of acute grade II–IV GvHD in patients receiving grafts with 0–1 HLA mismatched units compared with 2 mismatches, but it did not reach significance. In multivariate analysis, cell dose (TNC, CD34+) and HLA disparity were both not associated with grade II–IV acute or chronic GvHD risk. In this study, cryopreserved CD34+ cell dose of the single CB unit or engrafting unit in double CBT were independent predictors of neutrophil recovery rate. Although previous studies in single CBT demonstrate favorable associations between both cryopreserved and infused CD34+ cell dose and engraftment rate,3,4 the importance of CD34+ cell dose in double CBT is less clearly defined.5–7 Furthermore, most data in double CBT are based on infused cell doses, with only one study showing favorable engraftment with higher cryopreserved CD34+ cell dose of the engrafted unit.7 Currently, CD34+ cell content is not used to assist in CB unit selection at many transplant centers because measurements are not standardized. However, several recent studies show that post-thaw CD34+ cell measurements are closely correlated to cryopreserved values provided by different banks,7,8 which suggest that CD34+ measurements may not be significantly different despite different enumeration methods. On the other hand, we found no influence of higher cryopreserved TNC doses on the rate of neutrophil engraftment, possibly owing to the relatively high TNC dose of the CB units in our series. Another reason may be the wide variability of CD34+ cells (×105) to TNC (×107) ratio (0.62 ± 0.89 (s.d.)) among CB units supplied for transplant from the SCBB, which suggests that TNC content may not be a good predictor of graft hematopoietic reconstitution potential. Bone Marrow Transplantation (2015), 1 – 3
Our study in a predominantly non-Caucasian population found no significant associations of recipient race or donor–recipient racial match on outcomes in both single and double CBT. Although some studies identified higher GvHD risk in ethnic minorities,9,10 others have not identified any effect.11 Differences in outcomes between races may be contributed by more significant minor histocompatibility antigen disparity in minorities, lower socio-economic status, or the inability to find a well-matched appropriately-sized cord unit for transplant.10,12 Using our local CB bank, a majority (82%) could identify ⩾ 5/6 HLA-matched grafts, and recipients of different racial backgrounds received grafts that were similar in the extent of HLA matching. There is no data at present to suggest that donor race should be included as a factor in CB unit selection. Limitations of the current study are the small sample size, retrospective setting and heterogeneity of conditioning regimens and transplant procedures. Importantly, we lacked information regarding relapse or disease status at transplant, which limits the validity of the multivariate analysis for transplant outcomes. Race was reported by the transplant center and may not be reflective of true genetic race. In summary, we have demonstrated the importance of cryopreserved CD34+ cell dose in engraftment outcomes after unrelated single and double CBT. CD34+ cell content of CB units reported by cord blood banks may be potentially a more relevant cellular content to optimize outcomes. CONFLICT OF INTEREST The authors declare no conflict of interest.
S-Y Ong1, C Phipps1, P Chu2, A Prasath2, AYL Ho1, SJ Sobak2 and W Hwang1,2 1 Department of Haematology, Singapore General Hospital, Singapore and 2 Singapore Cord Blood bank, Singapore E-mail: [email protected] © 2015 Macmillan Publishers Limited
Letter to the Editor
3
REFERENCES 1 Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956. 2 Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Henslee-Downey PJ et al. IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol 1997; 97: 855–864. 3 Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C 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 2002; 100: 1611–1618. 4 Barker JN, Byam CE, Kernan NA, Lee SS, Hawke RM, Doshi KA et al. Availability of cord blood extends allogeneic hematopoietic stem cell transplant access to racial and ethnic minorities. Biol Blood Marrow Transplant 2010; 16: 1541–1548. 5 Avery S, Shi W, Lubin M, Gonzales AM, Heller G, Castro-Malaspina H et al. Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts. Blood 2011; 117: 3277–3285. 6 Rocha V, Crotta A, Ruggeri A, Purtill D, Boudjedir K, Herr AL et al. Double cord blood transplantation: Extending the use of unrelated umbilical cord blood cells
© 2015 Macmillan Publishers Limited
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for patients with hematological diseases. Best Pract Res Clin Haematol 2010; 23: 223–229. Purtill D, Smith K, Devlin S, Meagher R, Tonon J, Lubin M et al. Dominant unit CD34+ cell dose predicts engraftment after double-unit cord blood transplantation and is influenced by cord blood bank practice. Blood 2014; 124: 2905–2912. Kudo Y, Minegishi M, Seki O, Takahashi H, Suzuki A, Narita A et al. Quality assessment of umbilical cord blood units at the time of transplantation. Int J Hematol 2011; 93: 645–651. Oh H, Loberiza FR Jr, Zhang MJ, Ringden O, Akiyama H, Asai T et al. Comparison of graft-versus-host-disease and survival after HLA-identical sibling bone marrow transplantation in ethnic populations. Blood 2005; 105: 1408–1416. Ballen KK, Klein JP, Pedersen TL, Bhatla D, Duerst R, Kurtzberg J et al. Relationship of race/ethnicity and survival after single umbilical cord blood transplantation for adults and children with leukemia and myelodysplastic syndromes. Biol Blood Marrow Transplant 2012; 18: 903–912. Ustun C, Bachanova V, Shanley R, MacMillan ML, Majhail NS, Arora M et al. Importance of donor ethnicity/race matching in unrelated adult and cord blood allogeneic hematopoietic cell transplant. Leuk lymphoma 2014; 55: 358–364. Spierings E, Hendriks M, Absi L, Canossi A, Chhaya S, Crowley J et al. Phenotype frequencies of autosomal minor histocompatibility antigens display significant differences among populations. PLoS Genet 2007; 3: e103.
Bone Marrow Transplantation (2015), 1 – 3
