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.

Busulfan for Allogeneic Hematopoietic Stem Cell Transplantation in Children with Severe Aplastic Anemia: A Retrospective Study.

INTRODUCTION: This retrospective study aimed to compare a range of conditioning regimens in children with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the Seventh Medical Center of PLA General Hospital between January 2008 and June 2017. METHODS: Patients were categorized into the Bu (Bu + Flu + Cy + ATG-F regimen) and control (Flu + Cy + ATG-F) groups, with a median follow-up time after HSCT of 3.5 (range, 3.1-6.2) and 3.7 (3.2-5.9) years in the Bu and control groups, respectively. RESULTS: No differences were observed between the two groups regarding the median time of peripheral blood neutrophil and platelet engraftment (p = 0.538 and p = 0.491); the 28-day engraftment rates of neutrophils were similar (p = 0.199), although higher for platelets with Bu (p = 0.044). Additionally, graft failure was 0% and 20.0% in the Bu and control groups, respectively (p = 0.004). In both groups, the incidence of grades III-IV (or grades II-IV) acute graft-versus-host disease (GVHD) and chronic GVHD was not significantly different (p > 0.05). Moreover, the 3-year overall survival and failure-free survival did not show significant differences (p = 0.670 and p = 0.908). DISCUSSION: In children with SAA undergoing allo-HSCT, conditioning regimen with Bu + Flu + Cy + ATG-F is capable of enhancing the myeloablation effect, promoting donor hematopoietic stem cell engraftment, and reducing the graft failure rate. Furthermore, it does not increase the incidence of complications, including GVHD.

Intranasal Calcitonin Gene-Related Peptide Protects Against Focal Cerebral Ischemic Injury in Rats Through the Wnt/ß-Catenin Pathway.

BACKGROUND Intranasal calcitonin gene-related peptide (CGRP) delivery offers a noninvasive method of bypassing the blood-brain barrier for the delivery of CGRP to the brain. Here, we first reported the therapeutic benefits of intranasal CGRP delivery in rats following middle cerebral artery occlusion (MCAO). MATERIAL AND METHODS Real-time quantitative polymerase chain reaction (RT-qPCR) assay, enzyme-linked immunosorbent assay (ELISA), rat MCAO model, TTC (2, 3, 5-triphenyltetrazolium chloride) staining, hematoxylin and eosin (H & E) staining, Morris water maze test, TUNEL assay, immunofluorescence, and western blot assay were used to investigate the role of CGRP in rats. Cell Counting Kit-8 assay, colony formation assay, cell cycle assay, apoptosis assay, western blot assay, and TOP/FOP assay were used to investigate the role of CGRP in normal human astrocytes (NHA) cells. RESULTS The CGRP-MCAO-NDDS (nasal drug delivery system) group showed a significant reduction in the infarct volume and improvement in neurologic deficit tests of motor, sensory, reflex and vestibulo-motor functions compared to those rats in the CGRP-MCAO-IV group. CGRP markedly inhibited apoptosis and increased the expression of vascular endothelial growth factor (VEGF) and bFGF and decreased the expression of GAP43 in the cortex of MCAO rats. CGRP promoted cell proliferation and cell cycle process and inhibited cell apoptosis through the Wnt/ß-catenin pathway in NHA cells. CONCLUSIONS This noninvasive, simple, and cost-effective method is a potential treatment strategy for focal cerebral ischemic injury.

Efficacy and safety of human umbilical cord derived mesenchymal stem cell therapy in children with severe aplastic anemia following allogeneic hematopoietic stem cell transplantation: a retrospective case series of 37 patients.

The treatment of pediatric severe aplastic anemia (SAA) with allogeneic hematopoietic stem cell transplantation (allo-HSCT), presents major challenges including the risks of graft failure, septic complications, and graft-versus-host disease (GVHD). Additive infusions of human umbilical cord derived mesenchymal stem cell (hUC-MSC) may be administered to improve patient survival. We retrospectively examined 37 pediatric patients with SAA who received allo-HSCT and subsequent infusions of hUC-MSC suspension at a dose of 1.0 × 10(6 )/kg. The times and doses of hUC-MSC infusions were increased in patients with severe GVHD. All patients received hUC-MSC infusions. The median time to post-transplantation neutrophil count of greater than 0.5 × 10(9 )/L was 14 days (range, 11-20 days) and time to post-transplantation platelet count of greater than 20 × 10(9 )/L was 19 days (14-29 days). The overall frequency of acute GVHD (aGVHD) was 45.9% (17/37). These aGVHD episodes occurred at a median time of post-transplantation 47 days (15-83 days). The frequency of chronic GVHD (cGVHD) was 18.9% (7/37); cGVHD developed from aGVHD in 10.8% (4/37) of patients. The GVHD-associated mortality rate was 18.9% (7/37) and aGVHD-specific mortality rate was 8.1% (3/37). The median overall survival time was 35 months (9-67 months) and the three-year overall survival rate was 74.2% (28/37). Seven patients died of GVHD, one patient died of a severe invasive fungal infection, and one patient died of renal failure. In conclusion, post-transplantation hUC-MSC infusions seemed to be safely infused in children with SAA who have previously received allo-HSCT.

[Predicative significance of HRV and HRT to premature beat on patients with coal worker's pneumoconiosis].

OBJECTIVE: To determine the predicative significance of HRV and HRT to premature beat on patients with coal-worker's pneumoconiosis. METHODS: 100 coal-worker's pneumoconiosis patients with premature beat (including 44 cases of occasional ventricular premature contraction and 56 cases of frequent ventricular premature contraction) were chosen as CWP group, and 50 healthy coal workers were chosen as control group. 24 h DCG was used to monitor and analyze the change of premature beat and to calculate HRV. Index: SDNN, SDANN, HFLF, HRT: TO, TS, compare HRV of CWP group and control group and the changes of HRT of both occasional and frequent ventricular premature contraction. RESULTS: The incidence of CWP at night (66.1%, 37 cases) is higher than that during daytime (33.9%, 19 cases), and the difference is statistically significant with P < 0.05. HRV (SDNN SDANN HF HL) indexes of CWP group are lower than control group, and the difference is statistically significant with P < 0.05. HRV indexes of control group at night are higher than that during daytime, and the difference is statistically significant with P < 0.05. Comparison of CWP group HRV indexes between day and night is statistically insignificant with P > 0.05. Compared with control group, TO of CWP group is higher while TS is lower, and the difference is statistically significant with P < 0.05. Compared with occasional ventricular premature contraction patients in CWP group, TO of frequent ventricular premature contraction patients is higher while TS is lower, and the difference is statistically significant with P < 0.05. CONCLUSION: Frequent ventricular premature contraction group in CWP group suffer from severe impaired autonomic nervous function injury, and abnormal HRV and HRT can be prognostic indicator of frequent ventricular premature contraction among coal-worker's pneumoconiosis patients.

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.

[Clinical and molecular genetic analysis for a patient with glycogen storage disease â a].

OBJECTIVE: To investigate the mutation of glucose-6-phosphatase gene (G6PC gene) in a patient with glycogen storage disease Ⅰa. METHODS: PCR was used to amplify all five exons of G6PC gene. The PCR products were directly sequenced to detect the mutations. RESULTS: A heterozygous 743G>A mutation was found in the patient and his mother, resulting in the substitution of glycine (G) by arginine (R) in codon 222(G222R) in the putative membrane-spanning domain in human G6Pase, but not in his father and his sister. CONCLUSIONS: G222R mutation in G6PC gene was first identified in a patient with glycogen storage disease Ⅰa in mainland China.

Current research status of cytomegalovirus infection after hematopoietic stem cell transplantation: a bibliometric analysis.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an effective method for the treatment of hematological malignancies, severe aplastic anemia, and myelodysplastic syndromes. The most common infectious complication after HSCT is cytomegalovirus (CMV) infection. The purpose of this study was to analyze the status of research related to CMV infection after HSCT by conducting a literature search for CMV, hematopoietic, and stem cell transplantation. METHODS: The Science Citation Index Expanded (SCI-E) database in the Web of Science Core Collection (WOSCC) was used as the target database for our literature search. The subject search terms were CMV, hematopoietic, and stem cell transplantation, with the logical operation 'AND'. The search date range was from 1900 to June 15, 2021. We used CiteSpace software to analyze the literature. The analysis included: the annual change in the number of publications, the annual change in the number of references cited, the distribution of countries, the distribution of institutions, the distribution of journals, the distribution of authors, and the use of keywords. RESULTS: A total of 1,476 relevant documents were retrieved. The top 5 countries for number of publications were the United States, Germany, Japan, China, and Italy, while the top 5 countries for centrality scores were the United States, Australia, Germany, France, and Italy. The top 5 institutions for the number of publications were: Fred Hutchinson Cancer Research Center, the University of Washington, the University of Minnesota, Karolinska Institute, and Peking University. The top 4 institutions for centrality scores were: Fred Hutchinson Cancer Research Center, Henri-Mondor Hospital, the National Cancer Center, Karolinska University Hospital, and the University of Pavia. There were only 4 authors with a centrality score of 0.01. The literature was mainly published in top hematology journals and journals for immunization and transplantation. The top 5 keywords used were: cytomegalovirus, bone marrow transplantation, recipient, infection, and versus host disease. CONCLUSIONS: We found that CMV infection after HSCT has been attracting more and more attention by researchers, and that treatment has been the focus of current research.

Adaptive immunity-related gene expression profile is correlated with clinical phenotype in patients with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a common and lethal hematopoietic malignancy that is highly dependent on the immune microenvironment. However, light has yet to be shed on the landscape of adaptive immunity-related genes. This work aimed to uncover the novel molecular events in AML and potential therapeutic strategies for AML treatment. METHODS: For the current research, the transcriptional information of 732 genes that participate in adaptive immunity was collected from 173 patients with AML, and the patients were grouped into different cohorts based on the different expression patterns. The correlations between gene expression and clinical characteristics, including prognosis, were studied. RESULTS: According to the notably different expressions of adaptive immunity-related genes, the 173 patients were divided into 2 clusters and 3 subclusters. No significant differences in overall survival (OS) or progression-free survival (PFS) were detected between the clusters or subclusters. There were obvious discrepancies found in age, peripheral blood (PB) blast percentage, and French-American-British (FAB) classification between each cluster or subcluster. The patients in cluster 1 were older and more of them had M5 type; the patients in cluster 2 were younger and more of them had M2 type. Further, 81 genes were significantly correlated with age and 101 genes were significantly correlated with PB blast percentage. Comparison of the prognosis between each FAB type revealed that patients with M3 type displayed the most favorable OS and PFS. Among the differentially expressed genes (DEGs), CLEC2B expression was much lower in M2 patients than in patients with other types (P<0.001), and its high expression indicated a worse outcome (12.4 vs. 46.5 months of OS). CONCLUSIONS: This study has uncovered the expression profile of adaptive immunity-related genes in AML. The different gene expression patterns are not associated with survival, but are significantly correlated the FAB types. CLEC2B expression is low in patients with M2 type and is negatively correlated with prognosis, thus revealing a potential therapeutic target for AML.

A bibliometric analysis of the research on hematological tumor microenvironment.

BACKGROUND: In recent years, the incidence of hematological tumors has increased. The tumor microenvironment (TME) is the local biological environment in the process of tumor occurrence and development and is closely related to hematological malignancies, including lymphoma and leukemia. This study aims to conduct a bibliometric analysis of the research on the hematological TME, reflect the general situation of the research in this field, and remind the focus of future research. METHODS: Search the Science Citation Index Expanded (SCI-E) database on the Web of Science Core Collection (WOSCC). Use subject terms to search tumor microenvironment; the limited search subject is Hematology, and the time range is from 1990 to July 18, 2021. Use CiteSpace software to analyze the number of annual papers published, the number of citations, the distribution of disciplines, the distribution of countries/institutions, the distribution of authors, the distribution of journals, and the frequency of use of keywords and its trend of change. RESULTS: There were 1,992 related research articles cited 77,213 times. The top 5 countries with the number of published papers in this field are: the United States, Italy, China, Germany, and the United Kingdom; the top 5 centrally ranked countries are the United States, Italy, Spain, France, and Japan. Literature and cooperation are mainly from the United States. The top three researchers with several published papers are Anderson KC, Ansell SM, and Gascoyne RD. Their centrality scores are all low, with only 5 researchers reaching above 0.01, and there is less collaboration between the authors. High-quality papers are from Blood, Cancer Res, P Natl Acad Sci USA, and Nature. Keyword analysis shows that immunotherapy is the current focus of research in this field. CONCLUSIONS: The research on the microenvironment of hematological malignancies is rapidly developing. At present, the main research focus is on targeted immunotherapy.

Composition characteristics of the gut microbiota in infants and young children of under 6 years old between Beijing and Japan.

BACKGROUND: The composition of intestinal flora in Chinese and Japanese has been reported in many studies but that in infants aged 0-6 years old has not been studied yet. METHODS: The distribution characteristics of the fecal flora of infants in Beijing (n=84) and Japan (n=53) were analyzed using 16S rRNA gene sequencing analysis. RESULTS: This study showed the higher relative abundance of Erysipelotrichaceae_ UCG-003 and Anaerostipes in male group that of Ruminiclostridium, Eubacterium, Senegalimassilia and Senegalimassilia in female group, especially Senegalimassilia, which was not detected in male group. Defecation trait groups indicated significantly higher relative abundance of Bifidobacterium in abnormal bowel trait group than that in the normal group (P<0.05). The feeding groups' analysis showed significantly higher relative abundance of Bifidobacterium and Enterococcus and lower abundance of Bacteroides and Lacetospirillaceae in the breast-feeding group than that in the formula feeding and mixed-feeding groups. The relative abundance of Parasutterella and Ruminococcaceae_UCG-003 in the halitosis group was significantly higher than that in the normal group. The comparison of cold and fever group and normal group indicated significantly higher relative abundance of Erysipelatoclostridium and lower relative abundance of Lachnospiraceae _UCG-001 in the fever and cold group than that in the normal group (P<0.05). The regional comparison of intestinal flora of Beijing and Japan showed significant increase in the relative abundance of Bacillus, Lactobacillus, Prevotella, megamonas and Veillonella in the intestinal flora of 0-6 years old infants in Beijing. CONCLUSIONS: These findings improve the understanding of intestinal bacterial and viral communities of infants from the two Asian countries.

Foam cells promote atherosclerosis progression by releasing CXCL12.

BACKGROUND: Atherosclerosis (AS) is a chronic inflammatory disease that contributes to multiple cardiovascular diseases (CVDs), and foam cell formation plays important roles in the progression of AS. There is an urgent need to identify new molecular targets for treating AS, and thereby improve the quality of life and reduce the financial burden of individuals with CVD. METHODS: An in vitro model of AS was generated by treating THP-1 cells and human aortic vascular smooth muscle cells (HA-VSMCs) with oxidized low-density lipoproteins (ox-LDLs). HA-VSMC proliferation and foam cell formation were detected by the MTT assay and Oil Red O staining. C-X-C motif chemokine 12 (CXCL12) expression was suppressed by siRNA. An AS rat model was established by feeding rats a high-fat diet and vitamin D2 for 3 weeks. Histopathology examinations were conducted by Hematoxylin and Eosin (H&E) staining and the levels ionized calcium-binding adapter molecule 1 (IBA1) and α smooth muscle actin (α-SMA) expression were determined by ELISA assays and immunohistochemistry. RESULTS: An in vitro model of AS was established with THP-1 cells. CXCL12 expression in the model THP-1 cells was significantly increased when compared with its expression in control cells. Suppression of CXCL12 expression reduced the progression of AS in the cell model. Moreover, CXCL12 promoted AS in the in vivo rat model. CONCLUSION: Our results suggest that CXCL12 plays an important role in promoting the progression of AS. Furthermore, inhibition of CXCL12 might suppress the development of AS by inhibiting HA-VSMC proliferation and their transformation to foam cells.

Association of VEGF and VDR gene- gene and gene- smoking interaction on risk of multiple myeloma in Chinese Han population.

AIMS: To investigate the association of several single nucleotide polymorphisms (SNPs) within vascular endothelial growth factor (VEGF) and vitamin D receptor (VDR) gene polymorphisms and additional gene- gene and gene- smoking interaction with multiple myeloma (MM) risk in Chinese population. METHODS: Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate association between 6 SNPs within VEGF and VDR gene, additional gene- gene and gene- smoking interaction on MM risk. RESULTS: MM risk is significantly higher in carriers with the rs699947- A allele within VEGF gene than those with CC genotype (CA+ AA versus CC), adjusted OR (95%CI) =1.72 (1.19-2.33), and higher in carriers with rs2228570- T allele within VDR gene than those with CC genotype (CT+ TT versus CC), adjusted OR (95%CI) = 1.68 (1.26-2.17). We also found a significant two-locus model (p=0.0010) involving rs699947 and rs2228570, and a significant two-locus model (p=0.0107) involving rs2228570 andsmoking. Participants with rs699947- CA+AA and rs2228570- CT+TT genotype had the highest MM risk, compared to participants with rs699947- CC and rs2228570- CC genotype, OR (95%CI) = 3.12 (1.82 -4.61). Smokers with rs2228570- CT+TT genotype had the highest MM risk, compared to never- smokers with rs2228570- CC genotype, OR (95%CI) = 3.27 (1.74-4.86). CONCLUSIONS: We found that the A allele of rs699947 within VEGF and T allele of rs2228570 within VDR gene, interaction between rs699947 and rs2228570, rs2228570 andsmoking were all associated with increased MM risk.

Antiviral treatment of hepatitis B virus-transgenic mice by a marine organism, Styela plicata.

AIM: To evaluate the antiviral effect of the effective ingredient of Styela plicata in a murine model of hepatitis B virus carrier. METHODS: HBV-transgenic mice were divided into 3 groups (control group, lamivudine treatment group and the effective ingredient of Styela plicata treatment group) and assigned to receive normal diet, lamivudine or the effective ingredient of Styela plicata for consecutive weeks. Serum hepatitis B surface antigen was detected by enzyme-linked immunosorbent assay (ELISA) method. Serum HBV DNA was detected by real-time polymerase chain reaction (RT-PCR). Serum T helper (h) 1 cytokine interleukin (IL)-2 and Th2 cytokine IL-6 were detected by the quantitative sandwich enzyme immunoassay technique. Another group of HBV-transgenic mice was assigned to receive the effective ingredient of Styela plicata for consecutive weeks. The histology of liver tissue was evaluated before and after treatment. RESULTS: Twelve weeks after starting the therapy, serum hepatitis B surface antigen was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet (F(12wk) = 88.81, P(12wk) = 0.000<0.01). Serum HBV DNA was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet (F(12wk) = 20.71, P(12wk) = 0.000<0.01). However, like lamivudine, the effective ingredient of Styela plicata could not inhibit the replication of HBV completely. A rebound phenomenon of hepatitis B surface antigen and HBV DNA in sera could be found 4 wk after withdrawal of medication. Eight weeks after starting the therapy, serum levels before and after Styela plicata treatment of IL-2 were 2.41 +/- 0.38 and 10.56 +/- 0.78 ng/L, respectively (t(8wk) = -16.51, P(8wk) = 0.000<0.01). Compared with the serum levels of IL-2 in the normal diet-treated mice (2.48+/-0.17 ng/L; t(8wk) = 13.23, P(8wk) = 0.000<0.01). Serum levels before and after Styela plicata treatment of IL-6 were 63.62 +/- 6.31 and 54.52 +/- 6.22 ng/L, respectively, compared with the serum levels of IL-6 in the normal diet-treated mice (60.84 +/- 4.21 ng/L). Histological analysis of liver from Styela plicata-treated HBV-transgenic mice also showed catabatic status in inflammation and hepatitis B surface antigen. CONCLUSION: Styela plicata may be an effective antiviral medicine in treating chronic hepatitis B.

[Safety and effectiveness of tumor-ablative chemotherapy combined with low intensity modified conditioning regimen for 30 patients with hematologic malignancies receiving allogeneic hematopoietic stem cell transplantation].

This study was aimed to investigate the safety and effectiveness of tumor-ablative Chemotherapy combined with low intensity conditioning regiment BUCy/TBICy for patients with hematologic malignancies receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 30 patients with hematologic malignancies received above-mentioned therapeutic method from January 2012 to January 2013 was analyzed retrospectively, and the engraftment, GVHD, infection, conditioning-related toxicity, relapse and survival rates were evaluated. All the patients signed the informed consent before transplantation. The median follow-up duration was 20.5 (16.3-27.3) months. The results indicated that all the patients had been engrafted successfully. One year overall survival (OS) and disease-free survival (DFS) rates were 93.3% and 83.3% respectively. No conditioning-related toxicity occurred. The incidences of II-IV grade aGVHD was 37.9%, among which incidence of III-IV grade aGVHD was 3.4%; incidence of extensive cGVHD was 13.8%. So far, 1 case relapsed, 1 case displayed graft rejection, and poor function of graft occurred in 1 case, death occurred in 2 cases(6.7%). It is concluded that tumor-ablative chemotherapy combined with low intensity-modified BUCy/TBICy is safe and effective in allogeneic hematopoietic stem cell transplantation for hematologic malignancies, and it is useful to reduce relapse of hematologic malignancies after transplantation.

[Conditioning regimen containing fludarabine instead of cyclophosphamide for haploidentical hematopoietic stem cell transplantation].

OBJECTIVE: To explore the feasibility and safety of conditioning regimen containing fludarabine (Flud) for haploidentical hematopoietic stem cell transplantation (HSCT). METHODS: Preparative regimen containing Flud 40 mgxm(-2)xd(-1) on day -7 to -3 in place of cyclophosphamide (CTX) for haploidentical HSCT was given to 35 patients with hematologic malignancies (4 standard risk, 16 high risk, 15 relapse with no remission). All donors received rhG-CSF followed by HSC harvest. One patient received peripheral blood HSCT (PBSCT), one bone marrow transplantation (BMT), and the others BM combination with PBSCT. The regimen-associated side effect, engraftment, incidence of graft-versus-host disease (GVHD) and disease-free survival (DFS) probabilities were observed. RESULTS: All patients achieved sustained, full donor-type engraftment. Thirty-four patients obtained primary durable engraftment, and 1 who rejected graft from his mother obtained successful durable engraftment after the second graft from his father. The cumulative incidence of grade III-IV acute GVHD and chronic GVHD was 12.1% and 31.7%, respectively. With a follow-up duration of 8-25 months, 6 patients were dead, in which 3 died of relapse, 2 of acute GVHD, 1 of fungal infection, none died of regimen-associated side effect. The other 29 patients remained alive and DFS probability was 79.7%. CONCLUSION: Flud based conditioning regimens for haploidentical HSCT is safe and feasible, which reduces regimen-associated side effect, with no increasing the rate of relapse and infection, and decreases the incidence of aGVHD.