Hepatic injury following reduced intensity unrelated cord blood transplantation for adult patients with hematological diseases.

Liver injury is a common complication in allogeneic hematopoietic stem cell transplantation. Its major causes comprise graft-versus-host disease (GVHD), infection, and toxicities of preparative regimens and immunosuppressants; however, we have little information on liver injuries after reduced intensity cord blood transplantation (RICBT). We reviewed medical records of 104 recipients who underwent RICBT between March 2002 and May 2004 at Toranomon Hospital. Preparative regimen and GVHD prophylaxis comprised fludarabine/melphalan/total body irradiation and cyclosporine or tacrolimus. We assessed the etiology of liver injuries based on the clinical presentation, laboratory results, comorbid events, and imaging studies in 85 patients who achieved primary engraftment. The severity of liver dysfunction was assessed according to the National Cancer Institute Common Toxicity Criteria version 2.0. Hyperbilirubinemia was graded according to a report by Hogan et al (Blood. 2004;103:78-84). Moderate to very severe liver injuries were observed in 36 patients. Their causes included cholestatic liver disease (CLD) related to GVHD or sepsis (n = 15), GVHD (n = 7), cholangitis lenta (n = 5), and others (n = 9). Median onsets of CLD, GVHD, and cholangitis lenta were days 37, 40, and 22, respectively. Frequencies of grade 3-4 alanine aminotransferase elevation were comparable across the 3 types of hepatic injuries. Serum gamma-glutamil transpeptidase was not elevated in any patients with cholangitis lenta, whereas 27% and 40% of patients with CLD and GVHD, respectively, developed grade 3-4 gamma-glutamil transpeptidase elevation. Multivariate analysis identified 2 risk factors for hyperbilirubinemia; grade II-IV acute GVHD (relative risk, 2.23; 95% confidential interval, 1.11-4.47; P = .024) and blood stream infection (relative risk, 3.77; 95% confidential interval, 1.91-7.44; P = .00013). In conclusion, the present study has demonstrated that the hepatic injuries are significant problems after RICBT, and that GVHD and blood stream infection contribute to their pathogenesis.     

Unrelated umbilical cord blood transplantation in adult patients.

Since January 1996, we have administered myeloablative therapy followed by infusion of unrelated umbilical cord blood cells in 57 adult patients with high-risk disease. The median age was 31 years (range, 18-58 years), and the median weight was 70 kg (range, 46-110 kg). Two patients were treated for genetic disorders and 55 for advanced hematologic malignancies. The preparative regimens were total body irradiation or busulfan based, both with antithymocyte globulin. HLA matching between donor and recipient was 3 of 6 in 3 patients, 4 of 6 in 44 patients, 5 of 6 in 8 patients, and 6 of 6 in 2 patients. The median nucleated cell dose was 1.50 x 10(7)/kg (range, 0.54-2.78 x 10(7)/kg), and the median CD34(+) cell dose was 1.37 x 10(5)/kg (range, 0.02-12.45 x 10(5)/kg). All patients received granulocyte colony-stimulating factor after transplantation until neutrophil recovery. Graft-versus-host disease prophylaxis consisted of cyclosporine and steroids. The median number of days to an absolute neutrophil count of 500/microL was 26 (range, 12-55 days). The median time to an untransfused platelet count of >20000/microL was 84 days (range, 35-167 days). Seventeen patients developed grade II to IV acute GVHD. The median survival of the entire group was 91 days (range, 10-2251 days). Eleven patients were alive at a median follow-up of 1670 days (range, 67-2251 days), 1 with autologous recovery and 1 with relapsed lymphoma. The actuarial projected 3-year survival is 19%. Infection was the primary cause of death. These results suggest that unrelated umbilical cord blood transplantation is a viable option for adult patients and should be explored in patients with earlier-stage disease.     

Bloodstream infection after umbilical cord blood transplantation using reduced-intensity stem cell transplantation for adult patients.

Bloodstream infection (BSI) is a significant problem after cord blood transplantation (CBT). However, little information has been reported on BSI after reduced-intensity CBT (RI-CBT). We retrospectively reviewed the medical records of 102 patients. The median age of the patients was 55 years (range, 17-79 years). Preparative regimens comprised fludarabine 125 to 150 mg/m 2 , melphalan 80 to 140 mg/m 2 , or busulfan 8 mg/kg and total body irradiation 2 to 8 Gy. Prophylaxis against graft-versus-host disease comprised cyclosporin or tacrolimus. BSI developed within 100 days of RI-CBT in 32 patients. The cumulative incidence of BSI was 25% at day 30 and 32% at day 100. The median onset was day 15 (range, 1-98 days). Causative organisms included Pseudomonas aeruginosa (n = 12), Staphylococcus epidermidis (n = 11), Staphylococcus aureus (n = 6), Enterococcus faecium (n = 4), Enterococcus faecalis (n = 4), Stenotrophomonas maltophilia (n = 4), and others (n = 7). Of the 32 patients with BSI, 25 (84%) died within 100 days after RI-CBT. BSI was the direct cause of death in 8 patients (25%). Univariate analysis failed to identify any significant risk factors. BSI clearly represents a significant and fatal complication after RI-CBT. Further studies are warranted to determine clinical characteristics, identify patients at high risk of BSI, and establish therapeutic strategies.     

Allogeneic peripheral blood stem cell transplantation using reduced intensity versus myeloablative conditioning regimens for the treatment of leukemia

Reduced intensity conditioning (RIC) have allowed the application of transplantation to older patients and to patients with underlying medical problems. Between October, 1999, and June, 2003, 61 patients with acute leukemia or chronic myeloid leukemia received allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT) from HLA-identical siblings. Thirty-four were conditioned with myeloablative protocols and twenty-seven with RIC regimens. The patients in the myeloablative group were younger (29 vs. 37 years; p < 0.0003), most of them were transplanted in complete remission (74% vs. 59%; p < 0.03), had a shorter interval between diagnosis and HSCT (12 vs. 21 months; p < 0.02) and a greater proportion belonged to standard-risk prognosis (68% vs. 48%; p < 0.1). The median times to neutrophil, platelet and red blood cell engraftment for the myeloablative and RIC groups were 14 versus 11 days (p < 0.009), 17 versus 9 days (p < 0.0001), and 19 versus 12 days (p < 0.007), respectively. Transfusion requirements were lower in the RIC group. Severe mucositis was present in 32% and 7%, respectively (p < 0.01). The proportion of patients having acute graft versus-disease (GVHD), chronic GVHD, and infections was the same, as well as early and late mortality, disease-free survival, and overall survival. Analyzing all the patients together, three factors significantly influenced overall survival: standard risk patients, complete remission at transplant, and the absence of severe acute GVHD. In conclusion, our data suggest that even in high-risk patients, RIC transplantation seems to be as useful as ablative HSCT.     

Allogeneic hematopoietic cell transplantation following reduced intensity conditioning for treatment of myelofibrosis.

This report describes our experience with reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using matched sibling and unrelated donors (MUDs) for treatment of myelofibrosis (MF). Nine patients with MF (median age, 54 years) were treated with RIC allogeneic HCT using MUDs for 7 of the 9 patients and sibling donors for 2 patients. By the Lille classification, 4 patients were characterized as having high risk, 4 as having intermediate risk, and 1 as having low risk. The RIC regimen consisted of fludarabine and a single dose of total body irradiation for the first patient and fludarabine/melphalan for the remaining 8 patients. Granulocyte colony-stimulating factor-primed peripheral blood stem cells (PBSCs) were used for all but 1 patient who received a total of 3 products because of graft failure, of which 2 were bone marrow cells and the third was PBSCs. Prophylaxis against graft-versus-host disease consisted of cyclosporin/mycophenolate with or without methotrexate. Seven patients were successfully engrafted with white blood cells, with an absolute neutrophil count > or =500 by a median of day +15 (range, 10-21 days). At the time of final fluorescence in situ hybridization and/or short tandem repeat analysis, 8 of 9 patients were chimeric, with 96%-100% donor cells and/or DNA. Five of the 9 patients were alive at the time of final contact, with a median follow-up of 32.2 months for the living patients. Overall survival probability at 1 year was 55.6% (95% confidence interval, 31.3%-77.4%). These results suggest that RIC MUD HCT using PBSCs can be an effective treatment for older patients with MF.     

Invasive fungal infection following reduced-intensity cord blood transplantation for adult patients with hematologic diseases.

Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI.     

T-Cell recovery in adults and children following umbilical cord blood transplantation.

T-cell reconstitution following allogeneic stem cell transplantation may involve thymic education of donor-derived precursors or peripheral expansion of mature T cells transferred in the graft. T cell-receptor excision circles (sjTRECs) are generated within the thymus and identify new thymic emigrants and those that have not divided. We measured quantitative and qualitative immunologic reconstitution and sjTREC levels in adult and pediatric recipients of umbilical cord blood transplants (UCBTs). sjTRECs were detected at normal levels in all children, starting 12 months after transplantation. sjTRECs were not detected until 18 months after transplantation in adults, and then only at a 3-fold lower level than expected for age. We used complementarity-determining region 3 (CDR3) spectratyping to measure changes in T cell-receptor diversity occurring with restoration of thymic function. T-cell repertoires were skewed in adults and children at 12 to 18 months after transplantation but recovered to near-normal diversity at 2 to 3 years post-UCBT. T-cell repertoires appeared more diverse earlier in children (at 1 to 2 years post-UCBT) than in adults (at 3 to 4 years post-UCBT). We conclude that early T-cell recovery after UCBT occurs primarily through peripheral expansion of adoptively transferred donor T cells and results in skewing of the T-cell repertoire. The reappearance of sjTREC-containing cells after UCBT is associated with increasing numbers of phenotypicaly naive T cells, improved mitogen and recall antigen responses, and diversification of the T-cell repertoire. The delay in central T-cell recovery in adults relative to children may be due to differences in thymic function resulting from age-related atrophy, graft-versus-host disease, or the pharmacologic effects of prophylaxis and treatment of graft-versus-host disease.     

Paediatric umbilical cord blood transplantation

Umbilical cord blood is being used increasingly as a source of haematopoietic stem cells for transplantation because of rapid availability, and the unavailability of a HLA matched adult donor for some patients. This study reports the characteristics and outcomes of 15 patients who have undergone umbilical cord blood transplantation (UCBT) in Ireland between 1998 and 2009. The median total nucleated cell and CD34+ doses post-processing were 6.5 x 107cells/kg and 1.8 x 105 cells/kg, respectively. Median neutrophil recovery time was 30 days (range, 14-44). Median platelet recovery time was 46.5 days (range, 35-148). 33.3% of patients developed acute cutaneous graft-versus-host disease (GVHD) grade I-II. Three patients died of transplant-related toxicity and two died of leukaemic relapse. We conclude that, with a satisfactory stem cell dose, UCBT offers a high chance of engraftment with acceptable toxicity, and should be regarded as a favourable option in selected patients when satisfactory bone marrow or peripheral blood stem cell donors are not available.     

Double umbilical cord blood transplantation

Unrelated umbilical cord blood (UCB) is an alternative donor source for allogeneic haematopoietic cell transplantation and, compared with unrelated donor bone marrow, has the advantages of rapid availability, greater tolerance of HLA disparity and lower incidence of severe graft-versus-host disease. Graft cell dose is an important determinant of haematopoietic recovery and overall outcome following UCB transplantation, and the limited cell dose of single UCB units has been a major barrier to its more widespread use. Transplantation with two unrelated UCB units is feasible, safe and effective and can overcome the limitation of cell dose of single UCB units.     

Umbilical cord blood transplantation in adults using myeloablative and nonmyeloablative preparative regimens.

Unrelated umbilical cord blood (UCB) transplantation has recently been explored in an increasing number of adult patients. The relative ease of procurement and the lower-than-anticipated risk of severe acute graft-versus-host disease has made UCB transplantation an appealing alternative to bone marrow-derived hematopoietic stem cells. The use of reduced-intensity or nonmyeloablative preparative regimens to allow engraftment of UCB broadens the scope of patients who may benefit from allogeneic immunotherapy, including elderly and medically infirm patients with no matched sibling donor. This review summarizes the available data on the use of UCB as an alternative source of hematopoietic stem cell transplantation in adult patients.     

A meta-analysis of unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients.

Several studies have compared the results of unrelated donor bone marrow transplantation (UBMT) and unrelated donor cord blood transplantation (UCBT). To objectively analyze these data, we performed a systematic review and meta-analysis of pooled data on comparative studies of UCBT and UBMT in patients requiring hematopoietic stem cell transplantation. Combining the studies, 161 children and 316 adults undergoing UCBT (mostly 1 or 2 antigen-mismatched), along with 316 children and 996 adults undergoing UBMT (almost entirely fully matched with the recipient), were analyzed. T-cell-depleted UBMT was excluded; where data were available, only fully matched UBMT was used in the analysis. Pooled comparisons of studies of UCBT and UBMT in children found that the incidence of chronic graft-versus-host disease (GVHD) was lower with UCBT (relative risk [RR] = 0.26; 95% confidence interval [CI] = 0.12-0.57; P = .16), but the incidence of grade III-IV acute GVHD did not differ (RR = 1.46; 95% CI = 0.42-5.03; P = .55). There was no difference in 2-year OS in children when studies were pooled (RR = 0.76; 95% CI = 0.31-1.87; P = .55). For adults, transplantation-related mortality (pooled estimate, 1.04; 95% CI = 0.52-2.08; P = .91) and disease-free survival (DFS) (pooled estimate, 0.59; 95% CI = 0.18-1.96; P = .39) were not statistically different. Because of the unavailability of randomized controlled trials, pooled analysis of nonrandomized comparative studies was performed. Thus, our meta-analysis confirmed that UCBT in children and adults had consistently equivalent survival outcomes compared with UBMT despite greater donor-recipient HLA disparity with UCBT.     

Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. The disease typically presents in young boys and adolescent boys. Allogeneic bone marrow transplantation has been used to halt progression of the disease. However, many patients lack suitable HLA- matched related donors and must rely on unmatched donors for a source of stem cells. The purpose of this study was to evaluate outcomes of unrelated donor umbilical cord blood transplantation after chemotherapy-based myeloablative conditioning and retrospectively determine if baseline studies correlate and help predict outcome. Between November 22, 1996, and November 3, 2005, 12 boys with X-linked ALD who lacked HL- matched related donors were referred to Duke University Medical Center for transplantation. These children were conditioned with myeloablative therapy including busulfan, cyclophosphamide, and antithymocyte globulin before receiving umbilical cord-blood transplants from unrelated donors. Baseline studies of neurophysiologic, neuroimaging, and neurodevelopmental status were performed and patients were subsequently evaluated for survival, engraftment, graft-versus-host disease, and neurodevelopmental outcomes. A substudy evaluated whether baseline neuroimaging and neurophysiologic studies correlated with cognitive and motor function and if these studies were predictive of posttransplantation outcomes. The umbilical cord blood grafts had normal levels of very long chain fatty acids. They delivered a median of 6.98 x 10(7) nucleated cells per kilogram of recipient body weight and were discordant for up to 4 of 6 HLA markers. Neutrophil engraftment occurred at a median of 22.9 days after transplantation. Three patients had grade II-IV acute graft-versus-host disease; 2 had extensive chronic graft-versus-host disease. Cumulative incidence of overall survival of the group at 6 months is 66.7% (95% confidence interval 39.9-93.3%). Median follow-up was 3.3 years (range 12 days to 6.3 years). As previously reported with bone marrow transplantation, symptomatic patients faired poorly with lower survival and rapid deterioration of neurologic function. This study included 3 patients transplanted at a very young age (2.6-3.5 years) before the onset of clinical symptoms who continue to develop at a normal rate for 3-5 years posttransplant. Although baseline Loes scores correlated with cognitive and motor outcome, neurophysiologic studies failed to show statistically significant differences. Transplantation of boys with X-linked ALD using partial HLA-matched umbilical cord blood yields similar results to those previously reported after bone marrow transplantation. Superior outcomes were seen in neurologically asymptomatic boys less than 3.5 years of age at the time of transplantation. Baseline Loes scores were a strong predictor of cognitive and motor outcome.     

Adult recipients of umbilical cord blood transplants after nonmyeloablative preparative regimens.

We report the outcome of 13 patients with advanced malignancies who underwent nonmyeloablative conditioning therapy followed by infusion of partially matched unrelated cord blood cells. The median age of these patients was 49 years, and their median weight was 65.7 kg. The median nucleated cell dose infused was 2.07 x 10(7)/kg. Eight of the 13 patients demonstrated donor chimerism between 4 weeks and 6 months, and subsequent conversion to full donor chimerism was achieved in 5 patients. Three patients were alive and free of disease at 158 to 1054 days, with a median survival of 288 days after transplantation. The 100-day event-free survival is 69%, and overall survival is 77%. At 1 year, the event-free and overall survival was 43%. Treatment-related mortality observed within the first 100 days after transplantation was low: 1 previously extensively pretreated patient died of multiorgan failure. This result provides a basis for further exploring this potentially curative approach to selected patients who lack matched related or unrelated hematopoietic stem cell donors.     

Cytomegalovirus infections in adult T-cell leukemia patients

Cytomegalovirus (CMV) infection frequently occurred in patients with malignant lymphoma of T-cell origin, especially with adult T-cell leukemia (ATL). This was evidenced by histopathological examination at autopsy, isolation of CMV, and detection of CMV antibodies that indicate recent or active infection. Cellular immune response was suppressed in most ATL patients when examined by skin hypersensitivity reaction to purified protein derivatives (PPD), streptococcal antigens (SuPs), and phytohaemoagglutinin (PHA). None of the CMV-positive patients reacted to them. Thus, the presence of tumor cells of T-cell origin and the absence of skin hypersensitivity reaction seem to be risk factors for CMV infection. Each CMV isolate exhibited unique DNA fingerprints, suggesting that cross-infection of CMV did not occur among the ATL patients on the same ward.     

Double unrelated reduced-intensity umbilical cord blood transplantation in adults.

Umbilical cord blood (UBC) stem cells are a useful stem cell source for patients without matched related or unrelated donors. Adult transplantation with single UBC units is associated with high transplantation-related mortality (TRM). In most cases, mortality is due to infection related to slow engraftment and immunoincompetence. In this study, we used a reduced-intensity conditioning regimen of fludarabine, melphalan, and antithymocyte globulin followed by 2 partially matched UBC units. The UBC units were a 4/6 HLA match or better with each other and with the patient and achieved a minimum precryopreservation cell dose of 3.7 x 10(7) nucleated cells/kg. A total of 21 patients (median age, 49 years) were treated. The median time to an absolute neutrophil count > 0.5 x 10(9)/L was 20 days, and the median time to an unsupported platelet count > 20 x 10(9)/L was 41 days. Two patients experienced primary graft failure and underwent a second UBC transplantation. One patient had a late graft failure. Acute graft-versus-host disease (GVHD) grade II-IV occurred in 40% of patients. The 100-day TRM was 14%, and the 1-year disease-free survival was 67%. Mixed chimerism was associated with a higher risk of chronic GVHD. Our findings indicate that adult patients can tolerate double UBC transplantation well and achieve sustained antitumor responses using this reduced-intensity conditioning regimen.     

Allogeneic stem cell transplantation for patients with advanced hematological malignancies: comparison of fludarabine-based reduced intensity conditioning versus myeloablative conditioning

We compared the outcomes of allogeneic hematopoietic stem cell transplantation using reduced intensity and myeloablative conditioning for the treatment of patients with advanced hematological malignancies. A total of 75 adult patients received transplants from human leukocyte antigen-matched donors, coupled with either reduced intensity (n=40; fludarabine/melphalan, 28; fludarabine/cyclophosphamide, 12) or myeloablative conditioning (n=35, busufan/cyclophosphamide). The patients receiving reduced intensity conditioning were elderly, or exhibited contraindications for myeloablative conditioning. Neutrophil and platelet engraftment occurred more rapidly in the reduced intensity group (median, 9 days vs. 18 days in the myeloablative group, p<0.0001; median 12 days vs. 22 days in the myeloablative group, p=0.0001, respectively). Acute graft-versus-host disease (>or=grade II) occurred at comparable frequencies in both groups, while the incidence of hepatic veno-occlusive disease was lower in the reduced intensity group (3% vs. 20% in the myeloablative group, p=0.02). The overall 1-yr survival rates of the reduced intensity and myeloablative group patients were 44% and 15%, respectively (p=0.16). The results of present study indicate that patients with advanced hematological malignancies, even the elderly and those with major organ dysfunctions, might benefit from reduced intensity transplantation.     

Reduced-intensity conditioning stem cell transplantation: comparison of double umbilical cord blood and unrelated donor grafts

There are little data comparing umbilical cord blood (UBC) and conventional stem cell sources for reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT). We performed a retrospective analysis of RIC HCST using double UCB (dUCB) grafts and RIC HSCT using unrelated donor (URD) grafts. The study included 64 dUCB transplantations and 221 URD transplantations performed at Dana-Farber Cancer Institute and Massachusetts General Hospital between 2004 and 2008. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 14.1% for dUCB and 20.3% for URD (P = .32). The 2-year cumulative incidence of chronic GVHD was significantly lower in dUCB compared with URD (21.9% versus 53.9%; P < .0001). The 2-year cumulative incidence of nonrelapse mortality was significantly higher in dUCB (26.9% versus 10.4%; P = .0009). In our analysis, dUCB HSCT and URD HSCT had comparable 3-year overall survival (46% in dUCB and 50% in URD; P = .49) and progression-free survival (30% in dUCB and 40% in URD; P = .47). dUCBT was associated with greater nonrelapse mortality despite less chronic GVHD. Our findings suggest that the use of 2 partially matched UCB units appears to be a suitable alternative for patients undergoing RIC HSCT without an HLA-matched donor.     

Fludarabine-based reduced intensity conditioning for stem cell transplantation of Fanconi anemia patients from fully matched related and unrelated donors.

Reduced intensity conditioning has been suggested as a desirable therapeutic modality for the treatment of patients with malignant and nonmalignant indications, but it seems particularly attractive for patients with Fanconi anemia due to their increased sensitivity to chemoradiotherapy. Between November 1996 and September 2003, 7 patients (1 male and 6 female; age range, 3-31 years; median age, 9.5) were conditioned with a fludarabine-based protocol for stem cell transplantation without radiation. In vivo T-cell depletion was accomplished with anti-thymocytic globulin or Campath-1H (alemtuzumab). Graft-versus-host disease prophylaxis consisted of low-dose cyclosporine alone. Eight transplantations were carried out for 7 patients using bone marrow, peripheral blood, and/or cord blood as sources of stem cells. All patients received transplants from HLA-A, -B, -C, and -DR matched donors, 5 from family members and 2 from matched unrelated donors. One patient did not engraft her first matched unrelated donor and underwent a second transplantation from another matched unrelated donor, after which she engrafted well. All 7 patients are alive and well, fully reconstituted with donor cells, and with 100% performance status. In conclusion, fludarabine-based preparative protocols are well tolerated, facilitate rapid engraftment with minimal toxicity, and should be considered an essential component of choice for patients with Fanconi anemia.     

脐血细胞神经分化与移植的研究进展

自20年前Nakahata等发现人脐血中含有丰富的造血干细胞以来,脐血造血干,祖细胞的研究取得了很大的进展,并已成为一个新的造血干细胞来源。近来研究表明,脐血中的部分细胞在体外培养或体内移植后可分化为神经细胞,并可促进受损动物的神经功能恢复,本文将对脐血源神经细胞的研究进展进行探讨。