A Case of Female X-linked Chronic Granulomatous Disease Caused by X Chromosome Inactivation Treated with Hematopoietic Stem Cell Transplantation and Literature Review.

Objective: X-linked chronic granulomatous disease (X-CGD) is a rare primary immunodeficiency disease characterized by phagocyte dysfunction. It is caused by genetic mutations in the CYBB gene, predominantly affecting males. However, a small number of female carriers can also present with the disease due to biased X chromosome inactivation.1 This study aims to enhance the understanding of X-CGD in a rare case of an infant and young woman and provide insights into its diagnosis and treatment. Methodology: This study utilized various methods to investigate X-CGD in children and their parents. These methods included assessing neutrophil respiratory burst function, measuring gp91phox protein expression, analyzing chronic granuloma enzyme levels, conducting whole exon gene analysis, and evaluating X chromosome inactivation. Additionally, hematopoietic stem cell transplantation was performed using haploidentical donors from immediate family members. Results: The children in this study were found to be carriers of the CYBB gene mutation, and their neutrophil respiratory burst function was abnormal with no expression of the gp91phox protein. X chromosome inactivation analysis revealed a rate of 99.5%. Following hematopoietic stem cell transplantation, there was successful engraftment of granulocytes and megakaryocytes, with normalization of gene and enzyme examinations. Conclusion: The findings of this study highlight the importance of considering X-CGD in the diagnosis of children and women presenting with granulomatous disease. Furthermore, the use of hematopoietic stem cell transplantation was shown to achieve significant therapeutic effects in the treatment of X-CGD. Further research is warranted to explore early diagnostic strategies for X-CGD and to optimize the use of hematopoietic stem cell transplantation in managing the disease. Early diagnosis and intervention can lead to improved outcomes for patients with X-CGD. This study contributes to the understanding of X-CGD and its treatment by demonstrating the possibility of X-CGD in female carriers and the efficacy of hematopoietic stem cell transplantation. These findings emphasize the importance of early diagnosis and highlight the potential for successful outcomes in the management of X-CGD.

Effect of allogeneic hematopoietic stem cell transplantation for chronic granulomatous disease in children: A multicentre, retrospective cohort study in China.

Chronic granulomatous disease (CGD) in children is a rare primary immunodeficiency disorder that can lead to life-threatening infections and inflammatory complications. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly being used to treat severe CGD in children. We conducted a multicenter retrospective analysis of children with CGD who were treated with allo-HSCT at four pediatric hematopoietic stem cell transplant centers in China from September 2005 to December 2019. The study included a total of 171 patients (169 males and 2 females). The median age at the time of transplantation was 6.1 (0-16.4) years. Among them, 154 patients had X-linked recessive inheritance caused by CYBB gene mutations, 12 patients were autosomal recessive, 1 patient had DNAH11 and HYDIN gene mutations, and 4 patients had no gene mutations. The median follow-up period was 36.3 (1.9-79) months. All participating patients were applied to myeloablative conditioning (MAC) regimens. The rates of OS, EFS, and GEFS within three years were 87.5%, 85.3%, and 75.2%, respectively. The total graft failure and the total mortality rate were 5.3% and 11.1%. The cumulative incidence of acute GVHD was 53.8% and the incidence of chronic GVHD was 12.9%, The incidence of chronic GVHD was higher for patients who received unrelated donor cord blood stem cell transplantation (UD-CB) (P = 0.001). Chronic GVHD and coinfections are the risk factors for OS and EFS in patients with CGD after receiving allo-HSCT. UD-CB is a risk factor for EFS and the presence of pneumonia before transplantation is a risk factor for OS. In conclusion, through this study, we have demonstrated that allo-HSCT has excellent efficacy in the treatment of CGD in children, especially, RD-haplo is associated with a lower rate of graft failure incidence and mortality than the treatment modalities of other donor type. Therefore, allo-HSCT is strongly recommended when a well-matched donor is available. If a well-matched donor is not available, the HLA-mismatched donor should be carefully evaluated, and the conditioning regimen modified accordingly.

The novel HLA-DPB1*1497:01 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPB1*1497:01 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 4.

Case report: Curing a rare, unstable hemoglobin variant Hb Bristol-Alesha using haploidentical hematopoietic stem cell transplantation.

Unstable hemoglobinopathies are a rare, heterogeneous group of diseases that disrupt the stability of hemoglobin (Hb), leading to chronic hemolysis and anemia. Patients with severe phenotypes often require regular blood transfusions and iron chelation therapy. Although rare, studies have reported that hematopoietic stem cell transplantation (HSCT) seems to be an available curative approach in transfusion-dependent patients with unstable hemoglobinopathies. Here, we describe successful haploidentical HSCT for the treatment of an unstable Hb variant, Hb Bristol-Alesha, in a 6-year-old boy with severe anemia since early childhood. Two years after transplantation, he had a nearly normal hemoglobin level without evidence of hemolysis. DNA analysis showed complete chimerism of the donor cell origin, confirming full engraftment with normal erythropoiesis.

The research on the treatment of primary immunodeficiency diseases by hematopoietic stem cell transplantation: A bibliometric analysis from 2013 to 2022.

Hematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiency syndrome. The safety and efficacy of HSCT as a therapeutic option for primary immunodeficiency diseases (PID) have been studied by many research groups. The purpose of our study was to perform a bibliometric analysis of research on HSCT for the treatment of PID, to assess research trends in this field, and note future research priorities. The Web of Science Core Collection (WOSCC) was used to identify relevant publications. VOSviewer and CiteSpace software were used to analyze bibliometric parameters, such as yearly records, authors, grouped authors, countries, institutions, categories and keywords. There are 602 relevant records for the last decade (2013-2022). The top 5 productive authors and high-quality paper journals are listed. Reference co-citations analysis demonstrated recent research trends were "inborn errors of immunity," "gene editing," and "enteropathy." Research on HSCT for the treatment of PID has increased rapidly in the last decade, and bibliometrics are valuable for researchers to obtain an overview of hot categories, academic collaborations and trends in this study field.

Optimizing conditioning regimen with low-dose irradiation or busulfan enables the outcome of transplantation from a 6-7/8 HLA-matched donor comparable to that from an 8/8 HLA-matched unrelated donor in severe aplastic anemia patients under 40 years.

With the dramatic improvements in outcomes following alternative donor hematopoietic stem cell transplantation (HSCT), interest in the use of alternative donors in severe aplastic anemia (SAA) is increasing. We conducted a multicenter prospective study to explore the efficiency and safety of upfront HSCT from a 6-8/8 HLA-matched unrelated donor (MUD) or 6-7/8 HLA-matched related donor (MRD) in acquired SAA patients under 40 years. Between August 2014 and July 2017, 115 patients were enrolled, including 48 (41.7%) patients receiving grafts from an 8/8 MUD, 25 (21.7%) from a 6-7/8 MRD, and 42 (36.5%) from a 6-7/8 MUD. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was higher in the 6-7/8 MUD group than in the 8/8 MUD group (42.9% vs. 12.8%, P=0.001). The corresponding incidence in the 6-7/8 MRD group was comparable to that in the 8/8 MUD group (21.7% vs. 12.8%, P=0.332). There was no significant difference in the incidence of chronic GVHD (24.3%, 13.6%, and 17.9%, P=0.676), graft failure (2.4%, 8.0%, and 6.3%, P=0.551), overall survival (85.7%, 96.0%, and 87.5%, P=0.424), and failure-free survival (83.3%, 88.0%, and 83.3%, P=0.885) among the three groups (6-7/8 MUD, 6-7/8 MRD, and 8/8 MUD). In multivariate analysis, conditioning regimen without low-dose irradiation or busulfan was associated with an inferior failure-free survival (HR=2.973, P=0.042). In conclusion, after an intensified conditioning regimen with additional low-dose irradiation or busulfan, the outcome of HSCT from a 6-7/8 MRD or 6-7/8 MUD is comparable to that from an 8/8 MUD.

Improved outcomes using unmanipulated haploidentical hematopoietic stem cells combined with third-party umbilical cord blood transplantation for non-malignant diseases in children: The experience of a single center.

BACKGROUND: Unmanipulated haploid HSCT for SAA has resulted in improved outcomes over recent years. However, studies related to unmanipulated haploid HSCs combined with tp-UCB transplantation for other types of NMD are rare. Accordingly, we present the outcomes of 109 pediatric patients with life-threatening NMD undergoing unmanipulated haploid HSCs combined with tp-UCB transplantation. PROCEDURE: We retrospectively investigated 109 pediatric patients with life-threatening NMD treated with unmanipulated haploid HSCs combined with tp-UCB transplantation in a single center. RESULTS: The median days of neutrophil and platelet engraftment were +13 and +22 days, respectively. None of the cases experienced PGF. The incidence rates for grade I-II, III-IV aGVHD and cGVHD were 44.9%, 24.8%, and 9.3%, respectively. The incidence rates of CMV and EBV viremia were 46.7% and 39.4%, respectively. The median follow-up duration was 997 days. In total, 106 patients survived, including 104 cases with FFS and 2 cases with SGF. Three patients died. The 5-year TRM, OS, and FFS were 2.8%, 97.2%, and 96.2%, respectively. CONCLUSION: The results of unmanipulated haploid HSCs combined with tp-UCB in pediatric patients with life-threatening NMD were promising. However, further research is now needed to determine specific factors that might influence the engraftment of HSCs.

Prognosis of haploidentical hematopoietic stem cell transplantation in non-infant children with t(v;11q23)/MLL-rearranged B-cell acute lymphoblastic leukemia.

B-cell acute lymphoblastic leukemia (B-ALL) with MLL-rearrangements (MLL-r) is rare in pediatric patients (aged >1 year), and optimal treatment strategies remain unclear. This study aimed to retrospectively evaluate the clinical characteristics, outcomes, and effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) of 37 non-infant children with t(v;11q23)/MLL-r B-ALL. Their 4-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 69.8 %, 58.2 %, and 39.1 %, respectively, and differed significantly between patients receiving allo-HSCT (18/19 cases received haploidentical [haplo]-HSCT) at the first complete remission (HSCT at CR1, n = 19; 87.4 %, 89.5 % and 5.3 %) and those continuing consolidation therapy (Non-HSCT at CR1, n = 18; 52.2 %, 25.9 %, and 74.1 %, respectively), and the p values were 0.022, <0.001 and <0.001, respectively. Of the 13 patients experiencing relapse during consolidation chemotherapy, the five continuing with chemotherapy only died within 44 months, and the eight patients opting for allo-HSCT after CR2 had a 4-year OS of 57.1 %. Multivariate analysis revealed HSCT at CR1 as the only independent protective factor for OS, EFS, and CIR. The present results indicate that allo-HSCT (especially haplo-HSCT) at CR1 may decrease the relapse rate and improve the prognosis of non-infant children with t(v;11q23)/MLL-r B-ALL.

[A clinical study of haploid hematopoietic stem cells combined with third-party umbilical cord blood transplantation in the treatment of chronic granulomatous disease].

OBJECTIVE: To investigate the clinical efficacy of haploid hematopoietic stem cells (haplo-HSC) combined with third-party umbilical cord blood (tpCB) transplantation in the treatment of X-linked chronic granulomatous disease (X-CGD). METHODS: The clinical data of 26 boys with X-CGD were retrospectively analyzed who were admitted to the Sixth Medical Center of PLA General Hospital between April 2014 and March 2018. All the patients were treated with haplo-HSC combined with tpCB transplantation. The median age of the patients was 3.5 years. The donor was the father in 25 cases and an aunt in 1 case. Transplantation was 5/6 HLA-matched in 9 cases, 4/6 in 12 cases, and 3/6 in 5 cases. The patients received busulfan, cyclophosphamide, fludarabine, or anti-thymocyte globulin for myeloablative preconditioning. Cyclosporine A and mycophenolate mofetil were used for prevention of acute graft-versus-host disease (aGVHD). Then the patients were treated with haploid bone marrow hematopoietic stem cells combined with tpCB transplantation on day 1 and haploid peripheral hematopoietic stem cells on day 2. The counts of median donor total nucleated cells, CD34+ cells, and CD3+ cells were 14.6×108/kg, 5.86×106/kg, and 2.13×108/kg respectively. RESULTS: The median time to neutrophil and platelet engraftment was 12 and 23 days after transplantation respectively. Full donor hematopoietic chimerism was observed on day 30. Twenty-five cases were from haplo-HSC and 1 was from cord blood. No primary implant failure and implant dysfunction occurred, and secondary implant failure occurred in one case. The NADPH oxidase activity returned to normal one month after transplantation. The incidence of grade I-II aGVHD and grade III-IV aGVHD was 35% and 15% respectively. Chronic GVHD (cGVHD) of the skin occurred in one case, and no progression was observed after steroid administration. During the follow-up period of 6-51 months, 25 patients survived, of whom 24 were disease-free (23 patients without cGVHD and 1 with cGVHD of the skin) and NADPH oxidase activity returned to normal; one patient developed secondary implant failure but survived; one patient died of viral interstitial pneumonia 16 months after transplantation. The 5-year event-free survival rate and overall survival rate were 81%±12% and 89%±10% respectively. CONCLUSIONS: Haplo-HSC combined with tpCB transplantation is one of the effective methods for the treatment of X-CGD in children.

Clinical outcomes of unrelated cord blood transplantation in children with malignant and non-malignant diseases: Multicenter experience in China.

This multicenter retrospective study included 184 children with malignant and non-malignant diseases who underwent UCBT between January 1998 and August 2012. The malignant disease group included 101 children with ALL, AML, CML, JMML, and MDS, and the non-malignant disease group included 83 children with PID, ß-thalassemia, IMD BMF, and HLH. The median duration to neutrophil and platelet engraftment was 16 and 35 days in the malignant disease group vs 15 and 38 days in the non-malignant disease group. The cumulative incidence of grade II-IV aGVHD and cGVHD was 25.6% and 13.5% in the malignant disease group vs 19.7% and 11.1% in the non-malignant disease group, respectively. The median duration and cumulative incidence of neutrophil and platelet engraftment, and the cumulative incidence of grade II-IV aGVHD and cGVHD were similar between the two groups. Of the 184 pediatric patients, 114 patients survived during a median follow-up period of 14 months (range 4-138). The 5-year OS and DFS were not statistically different between the two groups (56.3% and 46.1% in malignant disease group vs 68.5% and 52.8% in non-malignant disease group). The above results indicate that UCB is a viable source for HSCT for children with malignant or non-malignant diseases, especially in urgent cases.

Similar outcomes of allogeneic hematopoietic cell transplantation from unrelated donor and umbilical cord blood vs. sibling donor for pediatric acute myeloid leukemia: Multicenter experience in China.

In a multicenter study, we have conducted a retrospective study on 73 pediatric AML patients who were primary refractory or in greater than CR1 and investigated MSD (or MMSD) (n = 20), URD (n = 23), and UCB (n = 30) HCT between January 1998 and October 2009. The median day to neutrophil engraftment was similar in all groups. The median day to platelet engraftment was longer in the UCB group. The number of HLA mismatch was higher in the UCB group (p = 0.034); however, the cumulative incidence of grade III-IV aGVHD was not different among all groups (p = 0.125); furthermore, cGVHD was lower in the UCB group (p = 0.078). The risk of relapse did not differ among all groups (RR = 1.28, p = 0.125), but the patients of MSD (or MMSD) grafts had a trend of higher risk recurrence. Sixty-two patients survived with a median follow-up of 58.2 months. Five-yr LFS was 73.1%, 59.8%, and 59.6% for URD, UCB, and MSD (or MMDS), respectively (p = 0.426). Five-yr LFS in CR1 was 68.9%, with a significantly better result compared to 41.7% in CR2 (p = 0.025). Our comparisons suggest that pediatric AML patients receiving UCB had a higher early TRM, a lower cGVHD rate, and a similar long-term survival. The outcome of URD and UCB is comparable to that of a suitable sibling for pediatric AML.

[Treatment of Gaucher disease with allogeneic hematopoietic stem cell transplantation: report of three cases and review of literatures].

OBJECTIVE: To explore the efficacy of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Gaucher disease. METHOD: The clinical characteristics of three children with Gaucher disease underwent UCBT in our hospital between April 2013 and September 2014 were retrospectively analyzed. Literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of Gaucher disease was searched at Wanfang and Pubmed databases between 1983 and 2015 and was reviewed and summaried. RESULT: Three children with Gaucher disease, all were female, received UCBT. These patients' age at receiving transplantation was 3.8 years, 7.1 years and 2.6 years, respectively. The second case received the second transplantation. The first and third case received splenectomy before UCBT. The pretreatment regimen was busulfan (Bu)/fludarabine (Flu)/cyclophosphamide (CTX)/antithymocyte globulin (ATG), and for the patient received the second transplantation melphalan was added to the myeloablative conditioning regimen of Bu/Flu/CTX/ATG. Cyclosporine and mycophenolate mofetil (MMF) wee used for prophylaxis of acute graft versus host disease (aGVHD). The dose of cord blood stem cell nucleated cell counts was 9.7 × 107 /kg,11.9 × 107 /kg and 7.6 × 107/kg respectively. The dose of cord blood stem cell CD34⁺ cell counts was 5.4 × 105/kg , 3.5 × 105/kg and 3.2 × 105/kg respectively. The day of granulocytes exceeding 0.5 × 109/L was day 11, 12 and 19 after transplantation, respectively. The day of platelets exceeding 20 × 109/L was day 14, 33 and 74 after transplantation, respectively. At one month after transplantation the rate of chimerism was over 95% and all patients got donor complete chimerism. The level of ß-glucocerebrosidase recovered to normal at one month after transplantation. During transplantation, all patients developed cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia. In case 1 immune thrombocytopenia occurred at five month after transplantation unresponding to steroids and mesenchymal stem cells infusion was administered and his platelet in routine blood test recovered to normal. But the patient died because she was infected with varicella-zoster virus out of hospital at nine month after transplantation and the level of ß-glucocerebrosidase was normal before death and chronic GVHD (cGVHD) was not found. The case 2 is now in 19th month after transplantation and his level of ß-glucocerebrosidase was normal. cGVHD was not found. The patient is currently free of disease. The case 3 was in 9th month after transplantation and his level of ß-glucocerebrosidase was normal. cGVHD was found at 112 day after transplantation and was localized and could be controlled by hormonal therapy. The patient is currently free of disease. Three patients' size of liver was significantly reduced after their level of ß-glucocerebrosidase ecovered. There were 50 cases with Gaucher disease who were treated with allo-HSCT in the literature and none of them were reported from China. Disease-free survival rate of patients treated with allo-HSCT for Gaucher disease was 85%. In all reports, there were 31 cases who had information of typing of Gaucher disease, of whom 22 cases had type 1 and 9 cases had type 3. Twenty-nine cases had information of survival, of whom 24 cases survived and 5 cases died of infection. Fifteen cases had data of engraftment, 2 of whom had graft failure and one had late graft failure.Glucocerebrosidase recovered to normal in 25 of 31 cases who had relevant data, in one of whom with late graft failure the enzyme recovered to normal 3 month after transplantation, but his enzyme decreased to the initial level 9 month after transplantation. Along with enzyme level's recovery to normal, in a part of cases bone pain and hepatomegaly were relieved and growth delay was improved. CONCLUSION: The unrelated UCBT may be a form of treatment that offers the potential of permanent cure and a procedure with possible long-term benefits in patients with Gaucher disease.

[Clinical effect of umbilical cord blood transplantation in 37 pediatric patients with hematologic malignancies: a single-center experience].

OBJECTIVE: To evaluate the clinical effect of umbilical cord blood transplantation (UCBT) in children with hematologic malignancies. METHODS: A retrospective analysis was performed on the clinical data of 37 pediatric patients with hematologic malignancies that consisted of 14 cases of acute lymphocyte leukemia, 9 cases of acute myeloid leukemia, 5 cases of juvenile myelomonocytic leukemia, 3 cases of chronic myeloid leukemia, 2 cases of acute mixed leukemia, 3 cases of myelodysplastic syndrome, and 1 case of lymphosarcomatous leukemia. Thirty-seven children with hematologic malignancies received UCBT from unrelated donors (34 cases) and related donors (3 cases). Grafts were 6/6 HLA-matched in 5 cases, 5/6 HLA-matched in 12 cases, 4/6 HLA-matched in 11 cases, and 3/6 HLA-matched in 9 cases. Before transplantation, these patients received rabbit antithymocyte globulin-containing conditioning regimen. The myeloablative conditioning regimen was given in 36 cases and the reduced-intensity conditioning regimen in one case. The median age of transplantation was 5.7 years, and the median weight was 20 kg. The grafts that contained a median of 6.2×10(7) total nucleated cells (TNC)/kg and 2.7×10(5) CD34(+) cells/kg were infused. RESULTS: The median times to neutrophil engraftment and platelet engraftment were 12 days and 25 days, respectively, and the rates of neutrophil engraftment and platelet engraftment were 95% and 78%, respectively. The rate of neutrophil engraftment was positively correlated with the number of CD34(+) cells (P=0.011), while the rate of platelet engraftment was correlated with the numbers of CD34(+) cells and TNC (P=0.001; P=0.014). The incidence rates of acute and chronic graft-versus-host disease were 49% and 11%, respectively. The median follow-up was 54 months. The 5-year transplant-related mortality, overall survival, and disease-free survival were 27%, 57.4% and 41%, respectively. CONCLUSIONS: UCBT is an alternative source of hematopoietic stem cells for patients with hematologic malignancies.

Long-term follow-up of autologous stem cell transplantation for severe paediatric systemic lupus erythematosus.

This study attempts to evaluate the outcome of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) in patients with severe paediatric systemic lupus erythematosus (SLE). Five patients (n = 2 females, n = 3 males) with severe or refractory paediatric SLE received autologous peripheral blood CD34+ cell transplants between July 2005 and February 2009. The patients ranged in age from 6 to 14 years, and the course of disease extended over a period from 5 to 90 months. All of the patients received conventional therapy for 3 to 87 months. After their discharge from the hospital, the patients continued to maintain their regular follow-up visits and basic quality of life. The patients exhibited decreased immune function after the auto-PBHSCT. The CD4+ and CD19+ cells were significantly reduced. Viremia occurred in four patients 2 months after the transplantation. All of the patients went into clinical remission in 3-6 months. The severity of encephalopathy, nephritis and organ damage declined in varying degrees. The disease recurred in patient 2 at 9 months and in patient 4 at 12 months after the transplantation. Because the disease was relatively mild, we were able to administer small doses of glucocorticoids that were sufficient to control the course of the disease. Macrophage activation syndrome occurred in patient 3 at 18 months after the transplantation. At the end of the follow-up period, three of the five patients were completely off their medications. Another two patients sustained small doses of glucocorticoids. The developmental levels of these patients were comparable to those of normal children at the end of the follow-up. The quality of life improved significantly. The auto-PBHSCT is effective for severe and refractory paediatric SLE. The incidence of lethal infection and other adverse reactions is low. Long-term remission can be achieved. A milder form of the disease may have recurred after the transplantation.

[Morphologic diagnosis and onset characteristics of acute leukemia: a retrospective analysis of 233 cases in 10 years].

The objective of this study was to evaluate the value of morphologic diagnosis for acute leukemia (AL), to explore the relation of morphologic diagnosis with immunology, cytogenetics and molecular biology diagnosis of AL and to analyze the onset characteristics of AL in 10 years. The samples of bone marrow and peripheral blood from 233 newly diagnosed cases of AL were collected during 2001-2011 years; the morphologic examination and immunologic, cytogenetic and molecular biologic examination (ICM) were carried out, the consistency of morphologic diagnosis with ICM diagnosis was compared, the onset characteristics of AL was analyzed. The results showed that: (1) the consistent rate of immunology, cytogenetics, molecular biology diagnosis with morphologic diagnosis was 84.3%. The order of consistent rat was AUL, M0 < M1 < HAL < M4 < M2 < M3 < M5 < ALL < M6, M7, AP; (2) Misdiagnosis always occurred among AUL, M0, M1, ALL and HAL or among M2a, M3v, M4 and M5. (3) In 233 cases, the highest ratio of blast was observed in M1 (92.5%), while the lowest ratio of blast was observed in M2 (49.5%). (4) AL occurred more frequently in males than that in female (147:86). (5) AL occurred in patients aged from 1 to 88 years. The median age was 41.5 for AUL, 40.8 for M0, 43.4 for M1, 46.3 for M2, 33.8 for M3, 42.6 for M4, 48.8 for M5, 77.3 for M6, 2.5 for M7, 65.0 for AP, 29.1 for ALL and 40.3 for HAL. (6) The number of patients in the later five years (139 cases) was significantly greater than that in the first five years (94 cases), especially the patients with M1, M2, M3, M4, and M5. It is concluded that morphologic diagnosis has important clinical value in the MICM diagnosis of AL. Attaching importance to the confusing cell morphology and onset characteristics of AL can improve the diagnostic accuracy.

[Comparison of total body irradiation-cyclophosphamide versus busulphan-cyclophosphamide as conditioning regimens for myelogenous leukemia: a meta-analysis].

Total body irradiation combined with cyclophosphamide (TBI/CY) and busulphan combined with cyclophosphamide (BU/CY) are standard conditioning regimens in hematological stem cell transplantation for patients with myelogenous leukemia. This study was aimed to compare the therapeutic efficacy of TBI/CY and BU/CY as conditioning regiment for acute or chronic myelogenous leukemia. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CNKI, CBM (Chinese Bio-medicine Database) had been searched for all relevant articles (1999-2007). Comparative studies were carried out on clinical therapeutic effects of TBI/CY and BU/CY including stem cell engraftment, relapse, complications, transplant-related mortality, and disease-free survival. A meta-analysis was performed using Review Manager 4.2 software and funnel plot regression was adopted to assess the publication bias. The results indicated that 2149 articles in English and 46 articles in Chinese were got, and finally 9 clinical trials with total 3039 patients have been assessed. No significantly difference was found in engraftment failure and transplant-related mortality resulting from TBI/CY and BU/CY conditioning regimens, but the incidence of veno-occlusion of liver and hemorrhagic cystitis obviously increased in BU/CY group after transplantation, the acute GVHD, interstitial pneumonia and cataract significantly increased in TBI/CY group. The relapse rate of AML in TBI/CY group was lower than that in BU/CY group, and the rate of long-term disease-free survival of AML patients in TBI/CY group also significantly lower than that in BU/CY group, but the relapse rate of CML in TBI/CY group after transplantation was obviously higher than that in BU/CY group, but there was no difference in longterm disease-free survival rate between the two conditioning regimens mentioned above. It is concluded that the meta-analysis confirms different effects of TBI/CY and BU/CY regimens on myelogenous leukemia transplantation. This result is useful for physicians to select treatment regimens.

[Unrelated umbilical cord blood transplantation as a treatment for children with malignant leukemia].

OBJECTIVE: Unrelated umbilical cord blood has the clear benefits of rapid availability and a reduced stringency of requirement for HLA match. The aim of this study was to investigate the efficacy of unrelated umbilical cord blood transplantation (UCBT) in the treatment of malignant leukemia in children. METHODS: Six children with malignant leukemia, including three cases of acute lymphocyte leukemia [two high-risk patients and one standard-risk patient in complete remission (CR)], two juvenile myelomonocytic leukemia (one in CR and one in the accelerating stage), and one acute myeloblastic leukaemia (in CR), received a UCBT. The umbilical cord blood grafts were HLA-matched (n=1) or HLA-mismatched at 1 (n=1) or 2 (n=1) or 3 (n=3) loci. Busulfan/cyclophosphamide/antithymocyte globulin (ATG) or total body irradiation (TBI)/cyclophosphamide/ATG was involved in the myeloablative pretreatment regimen. The median infused donor nucleated cell was 8.51 x 10(7)/kg of recipient weight, and the CD34+ cell was 1.81 x 10(5)/kg of recipient weight. Cyclosporin, corticoid, mycophenolate mofetil and daclizumab were used for prophylaxis of acute graft versus host disease (GVHD). RESULTS: The time to reach an absolute neutrophil count of 0.5 x 10(9)/L ranged from 11 to 35 days (median: 13 days) and the time to reach a platelet count of 20 x 10(9)/L ranged from 27 to 68 days (median: 30 days) after transplantation, and the donors' hematopoietic stem cells were shown in these patients. Four patients developed grade I to III acute GVHD but responded to steroids and daclizumab. Chronic GVHD was not found during a 3-16-month follow-up. Four patients survived and did not relapse during the follow-up. CONCLUSIONS: Unrelated umbilical cord blood is an alternative source of hematopoietic stem cells for patients with leukemia. UCBT can tolerate 1-2 HLA mismatches. The incidence of acute GVHD is high in UCBT recipients.

[Comparison of different cryopreservation systems for peripheral blood stem cells].

AIM: To explore proper cryopreservative systems for hematopoietic stem cells. METHODS: Peripheral blood mononuclear cells from 20 persons were mixed with different cryopreservative agent, dimethyl suflfoxide (DMSO) or combination of DMSO and hydroxyethyl starch (HES), then cooled in -80 degrees C low temperature refrigerator (Refr) or autocontrolled programmed cryogenic system (PCS), preserved in Refr or in liquid nitrogen. GM-CFU, LTC-IC, CD34+ cells and typeran blue resistance (TBR) were assayed after different period of cryopreservation. RESULTS: The recovery rates of CFU-GM, LTC-IC, CD34+ cells and TBR in peripheral blood mononuclear cells which were cooled and preserved in Refr with 5% DMSO-6% HES were 82.2% +/- 14.7%, 83.0% +/- 12.2%, 94.2% +/- 4.3% and 97.7% +/- 3.9% respectively, significantly higher than that in Refr with 10% DMSO (P < 0.05). When cells were cryopreservated with the same cryopreservatives, there was no significantly difference of recovery rate in group of Refr and group of Refr with PCS. Meanwhile, there was not significantly difference of recovery rate among all three groups, preserved in Refr ahead of liquid nitrogen, in Refr merely, in liquid nitrogen with PCS within one year (p > 0.05). However, the recovery rate of CFU-GM, LTC- IC, CD34+ cells and TBR decreased dramatically if cells were cooled and preserved in Refr for two years. After cells were thawed, the cell activity declined gradually at room temperature if the cryopreservatives were not removed or diluted. The cell activity of 10% DMSO group was affected more than that of 5% DMSO-6% HES group. CONCLUSION: 5% DMSO-6% HES is better than 10% DMSO as cryopreservatives for hematopoietic stem cells. Refr cryopreservation is a simple and effective method if cells would be cryopreserved for less than one year. If cells would be cryopreserved for more than one year, liquid nitrogen cryopreservation should be recommended. The cryopreservatives should be diluted or removed immediately after cells were thawed.