 |
 |
- Myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia: analysis of graft sources and long-term outcome. Tomblyn MB, Arora M, Baker KS, Blazar BR, Brunstein CG, Burns LJ, DeFor TE, Dusenbery KE, Kaufman DS, Kersey JH, MacMillan ML, McGlave PB, Miller JS, Orchard PJ, Slungaard A, Tomblyn MR, Vercellotti GM, Verneris MR, Wagner JE, Weisdorf DJ. J Clin Oncol. 2009 27;22:3634-3641.
This is a report of 25 years experience in myeloablative HCT for patients with ALL treated at the University of Minnesota. The authors compared the outcomes of HCT from related donors (RD), unrelated donors (URD), umbilical cord blood (UCB), and autologous donors. The study includes 623 consecutive patients undergoing myeloablative transplantation. The median age of patients was 13 years, ranging from 6 months to 55 years at transplant. 39% received a matched RD (n=245), 16% received URD grafts (n=100; 58 of 100 were HLA mismatched), and 11% received a UCB graft (n=69; 48 single, 21 double units).
After a median of 8.3 years of follow-up, 5-year overall survival, leukemia-free survival and relapse were 29%, 26% and 43%, respectively. Outcomes analysis revealed that mismatched URD sources yielded higher TRM and lower OS than RD or UCB HCT. Autografting yielded significantly more relapse and poorer LFS. HCT in first complete remission (CR1) yielded significantly better outcomes than later HCT. With RD, well-matched URD and UCB sources, 5-year LFS was 40%, 42%, and 49%, respectively, while relapse was 31%, 17%, and 27%. The authors concluded that allogeneic, but not autologous, HCT for ALL results in durable LFS. HCT in early remission can best exploit the potent antileukemic efficacy of allografting from UCB, RD, or URD sources.
In conclusion, the authors stated that their long-term analysis demonstrates that outcomes are similar for transplantation using RD, WM-URD, PM-URD, or UCB sources, and these may be considered equivalent options for patients with ALL. Autologous HCT should no longer be used for high-risk or relapsed ALL due to the unacceptably high relapse and poor long-term survival. Patients with ALL lacking a sibling donor can seek UCB (which yielded the best overall and leukemia free survival in this series), or a well-matched URD and have a good chance at long-term LFS.
- Hematopoietic cell transplantation for children with acute lymphoblastic leukemia in second complete remission: similar outcomes in recipients of unrelated marrow and umbilical cord blood versus marrow from HLA matched sibling donors. Smith AR, Baker KS, Defor TE, Verneris MR, Wagner JE, Macmillan ML. Biol Blood Marrow Transplant 2009;15:1086-103.
In many cases, allogeneic hematopoietic cell transplantation (HCT) has been considered only if a human leukocyte antigen (HLA) matched sibling donor (MSD) is available. As advances in supportive care and donor selection have improved, the use of URD HCT in such patients should be reevaluated.
The authors analyzed the outcomes of 87 consecutive children with ALL in CR2 who underwent allogeneic HCT at the University of Minnesota between 1990 and 2007. Donor sources included MSD bone marrow (n = 32), well and partially matched (M, n = 18) and mismatched (MM, n = 16) URD bone marrow, and URD umbilical cord blood (UCB, n = 21). Although the incidence of neutrophil recovery was similar in all groups, the overall incidence of grades II-IV acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) was 37% and 9%, respectively, with a higher incidence of aGVHD in recipients of URD grafts. Leukemia-free survival (LFS) at 5 years was lower in recipients of MM-URD grafts, but was comparable in all other groups. Although relapse at 5 years was highest in recipients of MSD (50%), results were not significantly different compared to recipients of M-URD (17%), MM-URD (6%), and UCB (33%) (P = .17).
In the Discussion section of the article, the authors state that their results suggest that transplant outcomes are remarkably similar in recipients of MSD, M-URD, and UCB grafts. Specifically, there were no obvious differences in LFS, risk of relapse, and most important, risk of early TRM. The authors also cite other studies suggesting similar outcomes in patients with ALL in CR2 regardless of donor source (Al-Kasinm et al., Br. J Haematol 2002;116:483-490; Munz et al., Pediatr Hematol Oncol 2008;25:245-259; Oakhill et al., Br H Haematol 1996;94:574-578).
The authors concluded that their results support the continued investigation of URD HCT for ALL in CR2, and suggest the timing of HCT in these children should be based primarily on the risk of relapse with conventional chemotherapy and not on the type of donor available.
- Disease-Free Survival After Cord Blood (CB) Transplantation Is Not Different to That After Related or Unrelated Donor Transplantation in Patients with Hematologic Malignancies. Doris Ponce, Junting Zheng, Anne Marie Gonzales, et al. Blood 2009;114:906 (Abstract 2296)
There are no randomized trials comparing survival after CBT with the more traditional approach of matched related donor transplantation (MRD-T) or unrelated donor transplantation (URD-T). Therefore, the investigators conducted a retrospective study comparing survival after CB-T (n=67) with MRD-T (n=96) and URD-T (n=163) for the treatment of hematologic malignancies.
Consecutive adult and pediatric recipients of first allograft for the treatment of acute leukemia in remission (CR1-3), myelodysplasia (MDS, ≤5% blasts at work-up), or non-Hodgkin’s or Hodgkin’s lymphoma were eligible for analysis. The median age of CB-T recipients (37 years) was not different to that of MRD-T (46 years) and URD-T (47 years) recipients. MRD grafts were HLA-identical whereas URD grafts were 8-10/10 HLA-allele matched. CB grafts were 4-6/6 HLA-A,-B antigen, DRB1 allele matched, with all CBT recipients receiving double unit grafts (median infused TNC larger unit 2.57 x 107/kg; smaller unit 1.93 x 107/kg) to augment engraftment.
Median follow-up of survivors is 22 months (range 5-46) and was similar between HSC sources. The data indicated no difference in the cumulative incidence (CI) of transplant-related mortality (TRM) at day 100 between HSC sources: 15% in CB-T as compared to 7% for MRD-T and 10% for URD-T recipients. Further, there was no difference in the CI of relapse at 1 year: 19% in CB-T as compared to 16% for MRD-T and 16% for URD-T recipients. Finally, by log-rank analysis there was no significant difference between HSC sources for either overall survival (p=0.778) or disease-free survival (DFS, p=0.381).
- Low relapse without excessive transplant-related mortality following myeloablative cord blood transplantation for acute leukemia in complete remission: a matched cohort analysis. Gutman JA, Leisenring W, Appelbaum FR, Woolfrey AE, Delaney C. Biol Blood Marrow Transplant. 2009;15:1122-1129.
Growing evidence supports the efficacy of cord blood transplantation (CBT), and the number of CBTs is increasing. The authors have observed a low relapse rate following CBT among patients with acute leukemias in morphologic complete remission (CR) at the time of myeloablative (MA) transplant. To further assess this observation, a matched cohort analysis was performed comparing relapse rates and outcomes for patients receiving CBTs versus patients receiving matched unrelated donor (MURD) and mismatched unrelated donor (MMURD) transplants at our center.
Thirty-one consecutive CBT patients (aged 0.6-42 years, median 22 years), transplanted between April 2006 and June 2008, were compared to matched subjects selected on the basis of disease type and remission number, cytogenetic risk status, minimal residual disease status (MRD), time from diagnosis to first relapse (for patients beyond CR1), use of imatinib for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) patients, age, and date of transplant. Twenty-seven of the cord blood transplant patients received 2 units and 4 received single units.
With a median follow-up among surviving CBT patients of 21.1 months (range: 6.6-32.6 months), there has been 1 relapse among cord blood transplant patients versus 8 relapses among MURD patients and 7 relapses among MMURD patients. Treatment-related mortality (TRM) between cohorts is comparable.
The authors indicate that their data suggest that patients undergoing myeloablative cord blood transplant for high-risk acute leukemias in morphologic CR have low relapse rates with acceptable TRM. The use of double-unit transplants may contribute to these results. The data suggest that consideration should be given to proceeding rapidly to transplants with cord blood units for patients with high-risk malignancies while disease status is under good control.
- Alternative haematopoietic stem cell sources for transplantation: place of umbilical cord blood. Smith AR, Wagner JE. Br J Haematol. 2009;147:246-261.
The purpose of this review is to provide the most recent information comparing the outcomes after umbilical cord blood transplantation with other stem cell sources (bone marrow and peripheral blood) for hematopoietic stem cell transplantation (HSCT).
While bone marrow (BM) and peripheral blood stem cell (PBSC) transplants have a proven track record of success, the search process takes 3-4 months, which is often longer than patients with high risk disease can wait. Despite almost 13 million registered volunteer donors worldwide, nearly half of patients still do not have a closely HLA-matched donor. The applicability of hematopoietic stem cell transplantation (HSCT) has markedly expanded with the introduction of umbilical cord blood (UCB), particularly for racial and ethnic minorities.
Differences in outcomes between UCBT and more traditional sources including BM and PPBSC are (1) the time to hematopoietic recover after UCBT is delayed, with the median time to neutrophil recovery ranging between 20 and 30 days in most reports, (2) cell doses has been shown to significantly influence the rate and incidence of hematopoietic recover after UCBT, (3) UCB is less restricted with regards to HLA matching such that a mismatch at one or two loci is well tolerated without a significant increase in GVHD or impaired survival, (4) the number of nucleated cells infused, and not the degree of HLA disparity, is the most significant predictor of success with UCBT (this permissive HLA mismatching improves the chances of finding a suitable unit for every patient, even those with unusual tissue types), (5) UCB units are rapidly available which becomes especially important when considering transplantation for rapidly progressive disease, and (6) UCB is viral pathogen-free with rare exceptions.
Conclusions differ by underlying disease and age of the patient:
Pediatric hematological malignancies: The authors review comparative outcome studies by Eapen et al 2006, Wall et al 2005, Sawczyn et al 2005, Kurtzberg et al 2008 and Eapen et al 2007. The largest of these studies (Eapen 2007) reported the outcomes of 785 children with acute leukemia. The most notable finding was that UCB compared favorably to the “gold standard” of 8/8 allele-matched unrelated BM. In fact the 5-year leukemia-free survival (LFS) was similar after 8/8 matched unrelated BM, mismatched unrelated bone marrow, and mismatched UCB with higher survival in recipients of matched UCB. This study was unique in that UCB was compared to the present day standard of allele-level matched BM donors.
Adult hematological malignancies: The authors reviewed older studies (Laughlin 2004, Rocha 2004) and a more recent study, Eapen 2008. The latter examined outcomes in 1240 adults; all unrelated donor BM and PBSC grafts were matched at allele level for HLA-A, -B, -C, and –DRB1. In this analysis, TRM was lower and LFS higher when matched unrelated BM and PBSC were used as compared to the other sources, suggesting that these graft sources are preferred when available and time permits. However, partially HLA-matched UCB with an adequate cell dose (≥2.5 x 107 nucleated cells/kg) is a suitable alternative when an HLA-matched adult donor product is not available or when the transplant is urgent.
Non-malignant disorders:
Hemoglobinopathies: Locatelli et al (2003) examined the outcomes in 44 patients who received related UCBT for either sickle cell disease (SCD) (n=11) or thalassemia (n=33) after a busulfan-based myeloablative preparative regimen. The 2-year overall survival (0S) was 100% and the event-free survival (EFS) was 79% for thalassemia and 90% for SCD. The rates of GVHD were low with only four patients developing acute and two patients developing chronic symptoms. These results clearly supported the use of related UCBT over related BMT due to the decreased risk of GVHD. A trial using a reduced intensity preparative regimen (Adamkiewicz, 2007) resulted in an EFS of only 43% as a result of graft failures, although the 2-year overall survival was 86%. For thalassemia, Jaing et al, 2008 reported a 3 year OS of 82% and DFS of 78% using optimized total nucleated cell doses.
Fanconi anemia: Wagner et al 2007, significantly improved engraftment (89% vs. 69%) and 3-year survival (52% vs. 13%) in those who received fludarabine versus no fludarabine. Increased mortality was ob served in patients >10 years old, CMV positive patients and those who had received >20 blood product transfusions prior to HSCT.
Metabolic storage diseases. UCBT is particularly desirable in these patients because the time from diagnosis to definitive treatment is crucial to prevent neurological disease progress and UCB units can be obtained quickly. Studies suggest that outcomes using CBT are at least as good as that seen with matched family donor BM. Prasad et al, 2008, reported results of 159 patients with inherited metabolic diseases who received CB transplants. Engraftment occurred in 87.1% and 1 year OS was 71.8%. Notably, those with high performance status had better OS (84.5%) emphasizing the importance of definitive treatment early in the course of the disease.
Reduced intensity conditioning (RIC): RIC has been explored as an alternative for patients deemed too high-risk for myeloablative conditioning such as those who are older, have been heavily pretreated and/or come to transplant with co-morbidities. Whether RIC is as effective in disease control as fully myeloablative conditioning is as yet unknown. In children, transplantation with RIC could potentially achieve the same goals as with myeloablative conditioning but with less toxicity. This is important because long-term effects are often more important in children. The first reports of RIC in children using CB transplants have been encouraging although these were retrospective results in heterogeneous groups of patients.
RIC is more commonly used in adults either because of older age or preexisting co-morbidities. A number of studies of RIC CB transplantation have been. For example, Brunstein et al, 2007, reported results in 110 adults transplanted for hematological disease. There was 92% sustained engraftment with 19% TRM and a 3-year OS of 45%, which is similar to those reported with other stem cell sources. Taken together with other available data, the results of studies thus far indicate that alternative donor RIC HSCT in adults is feasible with acceptable rates of TRM, GVHD and graft failure, thus extending the availability of transplantation therapy, especially to the elderly and those with co-morbid conditions.
Infections: Recent retrospective studies do not support the theory that serious infection is more common after CB transplantation in the pediatric population and that, although bacterial infections may be more common early after CB transplantation in adults, the risk of dying from infection is the same as the risk after other types of transplantation.
Donor-derived leukemia: In recent years, there have been several case reports of donor cell leukemia (DCL) after CB transplantation and it has been hypothesized that the incidence may be higher after CB transplantation when compared to other stem cell sources. However, it is estimated that the risk is still <1%, and there are no data to suggest that the risk is higher than that observed with other stem cell sources.
Double cord blood transplants: There has been a growing consensus that 2.5 x 107 nucleated cells/kg recipient body weight represents the CB cell dose threshold necessary for consistent engraftment. However, this cell dose is often not possible for adult recipients. Results reported in the last few years indicate that the co-infusion of two partially HLA-matched CB units is safe and efficacious, regardless of the intensity of the conditioning. It is at present unclear whether it offers any benefit other than extending the application of CB transplantation by virtue of achieving an adequate cell dose. Until data demonstrate a clear survival advantage, double CB transplants are only recommended for those patients who do not have an adequate single unit.
Cell dose recommendations: If an adequate cell dose using a single unit cannot be attained, a double cord blood transplant should be performed. An adequate single unit cell dose at the University of Minnesota has been defined as >3.0 x 107 TNC/kg for 6/6 HLA-matched units, >4.0 x 107 TNC/kg for 5/6 HLA-matched units and >5.0 x 107 TNC/kg for 4/6 HLA-matched units. While the exact cut off criteria for each degree of HLA mismatch is not known, the dose algorithm, in principle, is clear.
The authors provide several tables displaying detailed data to augment the text, including a table presenting general recommendations regarding the first, second and third choices of donor units (CB vs. adult stem cell sources) for malignant diseases and non-malignant diseases in children and adults.
- Cord blood transplantation for haematological malignancies: conditioning regimens, double cord transplant and infectious complications. Delaney C, Gutman JA, Appelbaum FR. Br J Haematol. 2009;147:207-216.
This review considers conditioning regimens for CB transplantation, the impact of double unit transplantation on CB outcomes, and data regarding infectious complications following CB transplantation.
Conditioning Regimens:
Total body irradiation (TBI)-based regimens: TBI continues to be the backbone of most myeloablative conditioning regimens. Given the heterogeneity of diseases treated, differences in age of patients, evolving standards for infused cell doses and degree of HLA matching, as well as varying additional therapies used in conjunction with TBI, it is not possible to draw conclusions regarding optimal TBI dose, dose rate, or fractionation schema.
In earlier series 120 mg/kg of cyclophosphamide (CY) and 90 mg/kg of equine ATG were commonly incorporated into regimens. More recently, however, the University of Minnesota has replaced ATG with 75 mg/m2 fludarabine. This change along with a change in post-transplantation immunosuppression from cyclosporine (CSA) and methylprednisolone to CSA and MMF has contributed to improvements in outcomes. The combination of 13.2 Gy TBI, 120 mg/kg CY and 75 mg/m2 fludarabine has now emerged as a standard myeloablative conditioning regimen at many centers. Other regimens have been investigated but small patient numbers prevent drawing conclusions regarding their relative efficacy for particular diseases, although they all appear to provide adequate immunosuppression to promote engraftment. As long as cell dose and HLA matching thresholds are met, more recent series consistently report >90% engraftment rates following myeloablative TBI-based conditioning. However, the toxicity of TBI-based regimens, especially in older patients, limits their widespread use. At the authors’ center, the current upper age limit for TBI CB transplantation conditioning regimens is 45 years.
Non-TBI based regimens: Development of non-high dose TBI-based conditioning regimens is an area of active investigation. Busulfan (BU) has been a cornerstone of many high dose non-TBI-based regimens, but the available data raises concerns about the engraftment potential of BU-based regimens. Addition of further immunosuppressive agents to BU-based regimens may facilitate engraftment, but raise concerns about regimen-related toxicities and further delaying immune reconstitution following CB transplants. At the Fred Hutchinson Cancer Center an investigation has been initiated of a treosulfan (TREO)-based conditioning regimen including 42 g/m2 TREO), 150 mg/m2 fludarabine and 2Gy TBI. A BU analogue, TREO is a novel agent that in vitro data suggests may have more potent anti-leukemic and immunosuppressive intensity than BU, and early clinical experience suggests it may be less toxic.
Melphalan dosed at varying intensities, has also been explored in several smaller studies of non-TBI based regimens, but may not be sufficiently immunosuppressive to ensure engraftment. The addition of either ATG or low dose TBI may, however, be sufficient to promote engraftment in melphalan-based regimens.
The University of Minnesota has pioneered a regimen of 200 mg/m2 FLU, 50 mg/kg CY, 2 Gy TBI ± 90 mg/kg equine ATG. In a series of 110 patients, primary neutrophil recover occurred in 92% of patients at a median of 12 days, and the cumulative incidence of sustained engraftment was 85%. The safety of this regimen has been confirmed for patients older than 55 years.
Double cord transplants: The NY Blood Center has recommended minimum TNC of ≥2.5 x 107/kg for 5/6 or 6/6 single unit transplants, and a minimum TNC of ≥5 x 107/kg for 4/6 matched single unit transplants. For many adults and large children, no single units are available that meet these cell dose requirements. Double unit CB transplants appear to have significantly increased engraftment rates among adults and older children and contributed to decreased TRM in these patients. In contrast to outcomes for adults in the COBLT trial, where the median pre-thaw TNC dose was 2.3 X 107/kg (range 1.4-5.5) and the cumulative incidence of neutrophil engraftment was 66%, a recent report by Barker et al indicates that using double cord blood units with a median infused TNC dose of 3.5 x 107/kg (range 1.1-6.3), 21 of 23 (91%) of patients achieved donor engraftment following myeloablative conditioning. Subsequent reports in the reduced intensity conditioning setting and larger series in the myeloablative setting have confirmed high engraftment rates following double unit CB transplantation among adults and large children. However, time to engraftment remains similar to that following single unit CB transplants. Moderate aGVHD seems to be increased compared to single unit CB transplants, though not with increased severe aGVHD or cGVHD. There may also be a decreased risk of relapse at least for patients with good disease control at the time of transplant. Double unit CB transplants have become standard practice at many centers for patients who do not have an adequately sized single unit.
Infectious complications: In some, but not all, registry comparative studies, deaths due to infection accounted for a higher proportion of early deaths among CB transplanted patients as compared to transplants using adult donors. Aggressive monitoring and supportive care for CB transplant patients appear to result in comparable long-term infection-related outcomes when compared to transplantation with stem cells from other donor sources.
CMV infection and disease have been reported to be significantly more likely in patients who were seropositive to CMV, in those with aGVHD, and in those receiving T-cell depleted grafts. Optimal CMV treatment strategies following CB transplantation are not defined. At the authors’ institution, an aggressive management strategy for CMV seropositive patients was instituted which includes 5 mg/kg ganciclovir IV once daily on days -8 to -2, and then high dose valacyclovir (2 g three times daily) or 500 mg acyclovir IV every 8 hours (or as appropriate for pediatric patients) up to day 100 post-transplant. Preliminary observations using this regimen indicate a significant reduction and delay in time to initial reactivation, and no cases of CMV disease. No cases of primary CMV infection have been observed among seronegative patients.
- Improving outcomes of cord blood transplantation: HLA matching, cell dose and other graft- and transplantation-related factors. Rocha V, Gluckman E; Eurocord-Netcord registry and European Blood and Marrow Transplant group. Br J Haematol. 2009;147:262-274.
This review focuses on the interactions between HLA, cell dose and other modifiable factors related to the UCB unit selection and transplantation that may improve outcomes after UCB transplantation. (The article concludes with a large and detailed table summarizing the authors’ recommendations regarding cord blood choice according to the number of HLA disparities, cell dose and diagnosis.)
Almost all series concerning CB transplantation from unrelated donors have demonstrated the profound impact of cell dose, measured as pre-freeze or infused total nucleated cells (TNC), colony forming cells, and CD34+ cells on engraftment, transplant-related events and survival. HLA matching was also recognized in the earlier series as an important factor for engraftment; however, its impact on long term survival, mainly in patients with malignant diseases is still controversial.
HLA and cell dose in myeloablative single unit CB transplants: Studies have reported that HLA matching and cell dose are crucial factors for improving outcomes after CB transplants and, in all probability, the number of TNC collected or infused should not be <2.5 or 2.0 x 107/kg (considering a loss of about 20%). Also, the number of HLA disparities should not exceed three out of six.
Results in children have also indicated that the TNC dose should be as high as possible, and should be >2.5 x 107/kg at collection. Results of outcomes of CB transplants in children with hematological malignancies have improved over the recent years as a result of higher numbers of TNC in CB grafts, lower number of HLA disparities, transplantation in early or intermediate phase of the diseases and, of course, other factors, such as supportive care and center experience.
Reduced intensity regimens: The number of adult patients transplanted with CB units has increased following the use of reduced intensity regimens and double CB transplants. Brunstein et al, 2007, have reported results of a study of CB transplantation using a non-myeloablative conditioning regimen consisting of fludarabine (200 mg/m2), CY (50 mg/kg) and a single fraction (200 Gy) of TBI, with ciclosporin and MMF for post-transplantation immunoprophylaxis. The target cell dose for the CB graft was 3.0 x 107 nucleated cells/kg resulting in the selection of a second partially HLA-matched CB unit in 85% of patients. 110 patients with hematological diseases were enrolled. Neutrophil recovery was 92% at a median of 12 days; TRM was 26% at 3 years; overall survival and EFS at 3 years were 45% and 38%, respectively.
Selection of CB units based on the interactions between cell dose, HLA disparities and diagnosis. Cell dose is the most important factor influencing outcome in patients with malignant diseases; a minimum of 3 x 107 TNC/kg at collection and 2 x 107 TNC/kg at infusion need to be targeted. The number of HLA mismatches increased the risk of delayed engraftment and led to a higher incidence of TRM and chronic GVHD, but decreased the risk of relapse resulting overall in a lack of influence of HLA mismatching on OS and DFS. The type of HLA mismatch did not influence outcome. The increasing the cell dose abrogated the effect of HLA mismatching, but not for grafts with 3 or 4 HLA incompatibilities.
Patients with non-malignant diseases should receive a higher cell dose to obtain engraftment than patients with a malignant disease; this should not be below 4.x 107 TNC/kg at collection and 3.5 x 107 TNC/kg at infusion. In non-malignant disorders, HLA mismatching played a major role in engraftment, GVHD, TRM, and survival that was partially abrogated by increasing cell dose. A CB graft containing two or more HLA disparities with a cell dose inferior to 3.5 x 107 TNC/kg should be avoided. Experience with double CB transplants in non-malignant disorders is still too limited to allow routine recommendations.
Other considerations when selecting a CB unit: The significance of HLA allele typing has been investigated but because the number of patients studied was too small to reach statistical significance. In fact, to determine the value of allele typing in CB transplants, thousands of patient-donor pairs will be needed to reach statistical significance.
Two studies of killer-immunoglobulin receptor (KIR) ligand matching have been performed but analyses of additional series of patients are needed before this factor can be included in the algorithm of CB choice.
ABO major incompatibility has been described to be associated with decreased survival and DFS in CB transplants for adults with hematological malignancies. Although these data are preliminary, if many cord blood units are available, the use of a unit that is ABO compatible or with minor incompatibilities should be taken into consideration.
Data are emerging that the patient’s pre-transplant ant-HLA antibodies also seem to have an impact on neutrophil and platelet engraftment after CB transplantation. The data suggest that patients with anti-HLA antibodies with specificities against the CB HLA antigens have lower neutrophil and platelet recovery. Therefore, patients’ pre-transplantation anti-HLA antibodies should be examined and considered when selecting CB units.
