Hematopoietic stem cell transplantation activity in China 2019: a report from the Chinese Blood and Marrow Transplantation Registry Group.

Between 2008 and 2019, 58,914 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) throughout China. In this report, we focus on 2019 data and describe current trends in HSCT in China. There was continued growth in transplant activity in China, with a rapid increase in haploidentical HSCT. In 2019, a total of 12,323 cases of HSCT were reported from 149 transplant teams, 78% (9597 cases) were allogeneic HSCTs. Haploidentical donor (HID) HSCT accounted for 60% (5771 cases) of allogeneic HSCT. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (AML) (37%) and acute lymphoblastic leukemia (ALL) (24%), and the largest proportion of non-malignant diseases comprised aplastic anemia (AA) (13%). Multiple stem cell source composed 70% of HID and 28% of MSD, which was typical in China. The BuCy based regimen (59%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu based regimen (23%) and TBI-based regimen (12%). This survey clearly shows comprehensive information about the current state and recent trends for HSCT in China. Further efforts should be made to obtain detailed information.

Haploidentical- versus identical-sibling transplant for high-risk pediatric AML: A multi-center study.

BACKGROUND: Human leukocyte antigen-identical sibling donor (ISD)-hematopoietic stem cell transplantation (SCT) is a potentially curative treatment for high-risk pediatric acute myeloid leukemia (AML). A haploidentical donor (HID) is readily available to almost all children. Previous studies have demonstrated that patients with HID-SCT had similar outcomes compared to ISD-SCT for pediatric and adult AML. However, the role of HID-SCT in high-risk pediatric AML is unclear. METHODS: To compare the overall survival of high-risk AML children who underwent either HID-SCT or ISD-SCT, we analyzed 179 cases of high-risk AML patients under 18 years of age treated with either ISD-SCT (n = 23) or HID-SCT (n = 156). Granulocyte colony-stimulating factor plus anti-thymocyte globulin-based regimens were used for HID-SCT. We also analyzed the subgroup data of AML patients at first complete remission (CR1) before SCT with known cytogenetic risk. RESULTS: The numbers of adverse cytogenetic risk recipients were 8 (34.8%) and 13 (18.8%) in the ISD-SCT group and the HID-SCT group, and the number of patients with disease status beyond CR1 were 6 (26.1%) and 14 (20.3%) in the two groups. The cumulative rates of grades II-IV acute graft-versus-host disease (GVHD) were 13.0% in the ISD-SCT group and 34.8% in the HID-SCT group (P = 0.062), with a three-year cumulative rates of chronic GVHD at 14.1% and 34.9%, respectively (P = 0.091). The relapse rate in the ISD-SCT group was significantly higher than that in the HID-SCT group (39.1% vs. 16.4%, P = 0.027); with non-relapse mortality at 0.0% and 10.6% (P = 0.113), respectively. The three-year overall survival rates were 73.0% for the ISD-SCT group and 74.6% for the HID-SCT group (P = 0.689). In subgroup analysis, the three-year relapse rate in the ISD-SCT group was higher than that in the HID-SCT group (50.0% vs. 9.2%, P = 0.001) and the three-year DFS in the ISD-SCT group (50.0%) was lower than that in the HID-SCT group (81.2%) (P = 0.021). CONCLUSIONS: Unmanipulated HID-SCT achieved DFS and OS outcomes comparable to those of ISD-SCT for high-risk pediatric AML patients with potentially higher rate but manageable GVHD.

[Nosocomial septicemia in the early stage after stem cell transplantation in children with major ß-thalassemia].

OBJECTIVE: To explore the clinical characteristics of nosocomial septicemia in the early stage after hematopoietic stem cell transplantation (HSCT) in children with major ß-thalassemia. METHODS: The clinical data were retrospectively analyzed of 55 consecutive children with major ß-thalassemia who developed septicemia early after HSCT between January, 2011 and June, 2016. RESULTS: Among the total of 416 consecutive children with major ß-thalassemia undergoing allogeneic HSCT, the incidence of nosocomial infection early after transplantation was 77.16% (321/416), and 55 (17.13%) children showed positive findings in blood culture test. The infections occurred most commonly in the oral cavity (65.5%), followed by the respiratory tract, intestinal tract and skin. Gram-negative bacteria, including Escherichia coli (27.3%), Klebsiella pneumoniae (21.8%) and Pseudomonas aeruginosa (9.1%), were the most common causes of infections. Fungal (Candida tropicalis) infection caused septicemia in 1 case. Of all the pathogens, extended-spectrum ß-lactamase (ESBL)-producing bacteria were found in 6 cases, methicillin-resistant Staphylococcus aureus (MRSA) in 2 cases, and multidrug-resistant (MDR) bacteria in 2 cases. CONCLUSION: Gram-negative bacteria are the major pathogens causing septicemia in children early after HSCT for major ß-thalassemia, and the bacteria show a high level of drug resistance. Adequate preventive use of antibiotics and care of the oral cavity, the respiratory tract, and the perianal region following the transplantation are important measures to control nosoconial infection in these children.

Clinical characteristics of acute lymphoblastic leukemia in male and female patients: A retrospective analysis of 705 patients.

The aim of the present study was to compare the clinical characteristics of acute lymphoblastic leukemia (ALL) that occurred in male and female patients at one institution in Southern China. The medical electronic records of Nanfang Hospital, affiliated to Southern Medical University, were searched for patients with a definite diagnosis of ALL that were diagnosed between January 1, 2001 and December 31, 2012. The clinical data of the patients were collected and analyzed. A total of 705 eligible patients were identified. The gender ratio of male to female patients was 1.84:1. The average ages at the time of diagnosis were 16.43 and 19.54 years for male and female patients, respectively (P=0.007). No significant differences were identified in the seasonal occurrence distribution, blood group distribution or ratio for the presence of the Ph chromosome between males and females. However, a higher incidence of T-cell type ALL was identified in males (P=0.023). The present study reveals that ALL demonstrates a male predominance, but similar clinical characteristics of ALL are present in males and females in Southern China.

[Outcome of childhood high-risk acute lymphoblastic leukemia treated with the ALL-BFM 95 protocol].

OBJECTIVE: To evaluate the effectiveness and the practicability of the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster 95 (ALL-BFM 95) protocol in treating childhood high-risk acute lymphoblastic leukemia (HR-ALL). METHODS: A retrospective analysis of 47 children with newly diagnosed HR-ALL between July 2003 and August 2013 was performed. These children were treated by the ALL-BFM 95 protocol. Survival was evaluated by Kaplan Meier analysis and Log-Rank test. RESULTS: Relapse-related death occurred in 12 of 47 patients (26%), and 5 of 47 patients (11%) were treatment-related mortality. Five-year probability of event-free-survival (pEFS) was 62%. Children with hematopoietic stem cell transplantation (HSCT) after chemotherapy achieved significantly better pEFS than those with chemotherapy alone (77% vs 52%; P=0.035). The patients who were only poor responders to prednisone had a better outcome (5-year pEFS 80%) than the Days 15 and 33 bone marrow M3 subgroups (5-year pEFS 60% and 0 respectively). CONCLUSIONS: ALL-BFM 95 protocol can improve the outcome of children with high-risk ALL. The major cause of death is attributed to relapse. Chemotherapy plus HSCT can produce a better outcome than chemotherapy alone. The Days 15 and 33 bone marrow M3 subgroups have a poor prognosis.

Assessment of iron overload in very young children with limited thalassemia care resources in South China.

Southern China has one of the world's largest population of patients needing transfusions. Transfusion and chelation are not uniformly available and no magnetic resonance imaging (MRI) assessment data exists to date. A total of 153 young ß-thalassemia major (ß-TM) patients were assessed using a validated 1.5T scanner in Hong Kong, People's Republic of China (PRC). Their median age was 13 (range 7 to 30), and most patients were young (22.0% age <10, 73.0% age <15, 88.0% age <18). Erratic health care made estimation of total transfusion and chelation exposure impossible. Despite their early age, 24.0% had severe cardiac hemosiderosis [T2*<10 milliseconds (ms)], at ages as early as 8 years old. Median heart iron was 1.68 mg/g dry weight (range 0.19-7.66) and increased with age (p = 0.017), while liver iron was 22.2 mg/g dry weight (range 3.15 to 39.2). Serum ferritin levels were poor predictors of heart and liver, or pancreatic R* and pituitary R* values. Magnetic resonance imaging scans are needed to screen very young ß-TM patients with immediate risk of premature cardiac death in developing nations and triage them to more intensive treatment. This is particularly important in countries with a large number of patients and limited resources. Our data suggests that in developing countries, there is no lower limit for thalassemia MRI scanning programs.

Allogeneic stem cell transplantation for children with acquired severe aplastic anaemia: a retrospective study by the Viva-Asia Blood and Marrow Transplantation Group.

We retrospectively analysed the outcomes of 127 children with acquired severe aplastic anaemia (SAA) who had received haematopoietic stem cell transplantation (HSCT) between 2000 and 2011 in one of the 10 Asia Pacific institutions. Fifty-three were matched sibling donor (MSD) and 74 were alternative donor (AD), including 22 matched unrelated donor, 32 mismatched unrelated donor and 20 mismatched related donor. With a median follow up 45.5 months (13-139) and when compared to the MSD group, AD recipients had more grade II-IV acute graft-versus-host disease (aGVHD; 14.3% vs. 32.8%, P = 0.029), but similar grade III-IV aGVHD (10.2% vs. 12.5%, P = 0.774), graft failure (GF) (15.1% vs. 15.5%, P = 0.658) and 5-year overall survival (90.6% vs. 83.7%, P = 0.251). As a source of stem cell, peripheral blood stem cells (PBSC) resulted in less GF (18% vs. 9.1% P = 0.013), similar grade II-IV aGVHD (28.1% vs. 17.4%, P = 0.258), chronic GVHD (25.8% vs. 29.3%, P = 0.822) and similar outcomes (89.7% vs. 82.4%, P =0.665) when compared to bone marrow (BM). In univariate analysis, GF (P < 0.001) and grade II-IV aGVHD (P = 0.009) were predictors of poor survival. In multivariate analysis, only GF was associated with poor survival (P = 0.012). The outcome of AD and PBSC HSCT were comparable to that of MSD and BM HSCT in the Asia Pacific region.

[Analysis of the risk factors for hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation for beta-thalassemia in children].

OBJECTIVE: To analyze the risk factors of hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation for beta-thalassemia in children. METHODS: The clinical records of 30 children with beta-thalassemia undergoing allogeneic hematopoietic stem cell transplantation between December, 2008 and November, 2009 were analyzed. RESULTS: Hemorrhagic cystitis occurred in 8 of the 33 patients with an incidence of 24.24%, including 1 with grade I, 6 with grade II and 1 with grade III hemorrhagic cystitis. The median time of hemorrhagic cystitis onset was 22.9 days (range 6-35 days) and the median duration was 11.9 days(range 3-27 days). Univariate analysis indicated that the different types of transplantation and acute graft-versus-host disease affect the occurrence of hemorrhagic cystitis. The children with Allo-PBSCT had higher incidence than those receiving Allo-PBSCT+Allo-UBT and Allo-BMT (P<0.05). The children at an age >or=6 years had obviously higher incidence of hemorrhagic cystitis than those at younger ages. CONCLUSION: Age is the major factor that affects the occurrence of hemorrhagic cystitis in children undergoing allogeneic hematopoietic stem cell transplantation for beta-thalassemia.

Thalassemia incidence and treatment in China with special reference to Shenzhen City and Guangdong province.

According to the data from different screening studies, thalassemia is the most commonly seen hereditary hemolytic disease in China. The reported prevalence of thalassemia carriers varies but it is most prevalent in Southern China. In the past, the outcome of patients with thalassemia major has been very poor due to unfavorable economic background. With economic improvement in the past 10 years, increasing number of patients can get regular transfusion and chelation, and more patients can be treated by hemopoietic stem cell transplantation. A better prevention network has been built up over the years, but there are still babies being born with severe forms of thalassemia every year. A more comprehensive preventive program and public education are vital.

[Effect of FK506 and CSA on the cell survival of engrafted HSC and the level of IL-2 and IL-4 in leukemia mice].

OBJECTIVE: To explore the effect of FK506 and CSA on the survival of HSCs and the level of IL-2 and IL-4. METHODS: The WEHI23 cells were injected into vein from tail of mice to set up the leukemia model. The Hematopoietic stem cells (HSCs) were harvested from GFP mice and cultured in vitro, then injected into the vein of leukemia mice. FK506 and CSA, as two immunosuppress agents, were applied in leukemia mice and intact mice, and leukemia mice were as control. RESULTS: Some HSCs could survive in the host treated with FK506 and CSA at least 2 weeks, while HSCs survived only 1 week in intact or leukemia control mice. Simultaneously, the level of IL-2 and IL-4 in leukemia mice treated with FK506 and CSA decreased significantly than those of intact or leukemia control mice. CONCLUSION: FK506 can promote the survival of HSCs in host, and the mechanism may be associated with the down regulation of IL-2 and IL-4.

[Effects of mouse bone marrow mesenchymal stem cells on the expression of chemokine receptors of spleenocytes after phytohemagglutinin stimulation].

OBJECTIVE: To explore the effect of mouse bone marrow mesenchymal stem cells (MSCs) on the expression of chemokine receptors in T lymphocytes in vitro. METHODS: Mouse bone marrow MSCs were separated with Percoll, cultured and expanded in low glucose DMEM. C57BL/6 mouse spleenocytes were cultured in the 24-hole flasks by the density of 1 x10(6)/hole. Phytohemagglutinin (PHA) was then added to the holes and cultured for 72 hrs. This study consisted of three groups. Groups A and B were co-cultured by adding MSCs as the ratio of 0.1 and 0.01 to spleenocytes respectively. The control group was cultured without MSCs. Three days later the suspended spleenocytes were harvested for detecting the expression of three chemokine receptors CXCR3, CCR5 and CCR7 in T lymphocytes by the flow cytometry. RESULTS: The expression of CD3(+)CCR5(+) and CD3(+)CCR7(+) were statistically different among the three groups. Group A had the strongest expression, followed by group B and the control group. The expression of CD3(+)CXCR3(+) in group A was statistically higher than that in group B and the control group. CONCLUSIONS: MSCs could up-regulate the expression of chemokine receptors CXCR3, CCR5 and CCR7 in T lymphocytes stimulated by PHA.

[Analysis of therapeutic effectiveness of Nanfang ALL 99 protocol in childhood acute lymphoblastic leukemia patients].

OBJECTIVE: With more precise diagnostic criteria and risk classifications, more effective therapy administered in clinical trials, and better supportive care, the outcome of children with acute lymphoblastic leukemia (ALL) has been improved dramatically. Today, approximately 80% of children treated for this disease in developed countries enjoy long-term event free survival (EFS) and in most instances, would be cured. In this study, treatment outcome of 82 childhood ALL patients in the hospital were analyzed, and ways for how to improve the EFS rate in childhood ALL were explored. METHODS: Eighty-two patients with ALL were enrolled into the Nanfang ALL 99 protocol which derived from German BFM ALL 95 and Hong Kong-Singapore acute lymphoblastic leukemia 97 (HK-SG ALL 97). Dexamethasone instead of hydrocortisone was used for triple intrathecal therapy. Standard at risk patients who had been irregularly treated in other hospitals for short periods of time were classified as at intermediate risk. When ANC was > or = 1.0 x 10(9)/L and platelet > or = 100 x 10(9)/L, chemotherapy was started. Life table method was used to estimate survival rate and statistical analysis was done by using software SPSS for Windows. RESULTS: From March 1999 to September 2003, 82 childhood ALL patients were treated with the Nanfang ALL 99 protocol and 78 (95.1%) patients attained complete remission (CR) in a median time of 33 days. Out of 82 patients, 13 patients dropped out of the the Nanfang ALL 99 protocol because of financial difficulty or other reasons. Sixty nine patients were consecutively treated with the Nanfang ALL 99 protocol. The overall EFS rate at 2 years, 3 years and 5 years were 91.3%, 85.9% and 75.2%, respectively, with a median observation duration of 34 months. Three patients died of complications (4.3%). The disease relapsed in 6 patients and they died finally. CONCLUSION: The outcome of patients treated with the Nanfang ALL 99 protocol was favorable, and the mortality rate of this chemotherapeutic protocol was low. This protocol was well tolerated by Chinese patients and therefore the protocol is worthy of application in China.

[Allogeneic hematopoietic stem cell transplantation for beta-thalassemia major].

OBJECTIVE: To investigate the effect of hematopoietic stem cell transplantation (HSCT) for beta-thalassemia major. METHODS: Fifteen beta-thalassemia major patients with a median age of 3. 5 years (range 1 - 10 years) received allogeneic HSCT. According to the Pesaro's classification for thalassemia, 12 patients were grade I - II, and 3 grade III. The bone marrow transplantation (BMT) plus peripheral blood stem cell (PBSC) transplant mobilized by granulocyte colony-stimulating factor (G-CSF) was used when donor is low body-weight. RESULT: Of the fifteen patients, nine were disease-free survival (DFS) at a median follow-up of 2.5 years (range 6 - 54 months). Of eight grade I - II patients received HLA identical sibling BMT, seven were DFS, and of two received HLA mismatched marrow from their mother, one DFS, another not engrafted. Two patients received unrelated cord blood HSCT were both not engrafted. Two patients received PBSC transplantation alone were not engrafted, but one of them soon received BMT from the same donor and was DFS. The incidences of grade I - II and grade III acute graft-versus-host disease (aGVHD) were 20% (3/15) and 6.7% (1/15), respectively. Interstitial pneumonia occurred in 4/15 (26.7%) patients. There were no long-term complications in the survivors. CONCLUSION: Grade I - II beta-thalassemia major patients received HLA identical sibling BMT had higher DFS. It was propitious for engraftment to use BMT plus PBSC, but with a higher incidence of acute and chronic GVHD.

Mixed hematopoietic chimerism for preventing graft-versus-host disease in mice receiving rat bone marrow transplantation.

OBJECTIVE: To find a method for preventing graft-versus-host disease (GVHD) in BALB/c mice receiving rat bone marrow transplantation. METHODS: Firstly 12 SD rats were conditioned with 5.0 Gy sublethal total body irradiation(TBI), followed by infusion of 8 x 10(7) bone marrow cells from 28 BALB/c mice within 4 h and intraperitoneal administration of 100 mg/kg cyclophosphamide (Cy) 2 d later, for the purpose of inducing chimeric SD rats with specific immunological tolerance. Secondly, 24 BALB/c mice were exposed to 9.0 Gy lethal TBI and divided randomly into 3 equal groups designated respectively as groups A, B and C. Mice in group A were injected with 4 x 10(7) bone marrow cells from 4 normal rats, and mice in group B were injected with 4 x 10(7) bone marrow cells and 2 x 10(7) spleen cells from 4 normal rats, while those in group C were given 4 x 10(7) bone marrow cells and 2 x 10(7) spleen cells from 6 chimeric rats. The mice were then observed for 150 d for GVHD. RESULTS: In the second procedure, 2 mice in group A failed to survive due to infection and radiation injury respectively, and none of the rest mice presented signs of GVHD. The mice in group B all developed GVHD of varied degrees with symptoms as wasting, diarrhea, fur loss, arched body posture, and even bloody stool, and all died within 5 to 15 d with an average survival of 10.0 d (95% confidence interval 8,12). Pathological examination of the liver and intestinal tissues revealed inflammatory lymphocyte infiltration and necrosis. The majority of the mice in group C, in contrast, survived for more than 150 d with only two died on the postoperative days 18 and 31 respectively. The survival time of group B was significantly shorter than that of the other two groups. CONCLUSION: Donor/recipient chimerism may help prevent GVHD in xenogeneic bone marrow transplantation.

[Animal model of rat-to-mouse xenogeneic bone marrow transplantation with graft-versus-host disease].

To observe the graft-versus-host disease (GVHD) in rat-to-mouse model of bone marrow transplantation to build a GVHD model, BALB/c mice were conditioned with 8.5 Gy lethal total body irradiation and divided into two groups. One group of mice was infused with 4 x 10(7) bone marrow cells (BMC) from SD rats. The other group of mice was infused with 4 x 10(7) bone marrow cell and 2 x 10(7) spleen cells from SD rats. GVHD in mice of two groups were observed for 60 days. The results showed that mice in the group infused with only BMC mostly (80%) survived more than 60 days, but in the other group infused with mixed BMC and spleen cells, all mice died within 14 days and showed GVHD with pathologic evidence. In conclusion, to induce GVHD in rat-to-mouse bone marrow transplantation needs additional rat spleen cells.