Therapy preference and decision-making among patients with severe sickle cell anemia and their families

BACKGROUND: Patients with severe sickle cell anemia (SCA) may benefit from therapeutic intervention with hydroxyurea (HU), chronic red cell transfusion (CT), or stem cell transplantation (SCT). Determination of best treatment is complicated by the tradeoff between each treatment's risks and benefits and the lack of data comparing them to determine efficacy. We explored factors that influenced making decisions regarding interventions and examined the relations between treatment preference and health-related quality of life (HRQOL). METHODS: Children with severe SCA and their parents received brochures describing each treatment, discussed risk/benefits with a nurse-educator, and answered questions regarding HRQOL and the factors influencing treatment preference. Severe SCA was defined as >or=3 pain events requiring ER visits or hospitalizations within 12 months, >or=2 acute chest syndrome (ACS) events within 24 months, or a combination of the two. RESULTS: Thirty parents and 7 patients participated. HU was preferred by 21 parents and 4 children, CT by 5 parents and 1 child, and SCT by 3 parents and 1 child. One parent was undecided and one child preferred no treatment. Interviewees were most influenced by perceived efficacy and safety, but no factors differed significantly among treatment preference groups. HRQOL median scores (0-100 scale) for parents (56; range, 28-91) and children (61; range, 31-96) did not differ significantly among treatment preference groups. CONCLUSIONS: Patients with severe SCA and their parents can identify their treatment preferences. Improved understanding of their preferences and decision-making process will aid in the design of future clinical trials and in medical decision-making.     

Desire for biological parenthood and patient counseling on the risk of infertility among adolescents and adults with hemoglobinopathies

Background

Both diagnosis and treatment of hemoglobinopathies have been associated with an increased risk of fertility impairment. German guidelines recommend annual monitoring of fertility parameters to enable early detection of fertility impairment and/or to offer fertility preservation (FP) when indicated. We explored the general desire for parenthood, the frequency of recalling fertility counseling and testing, and the utilization of FP in adolescents and adults with hemoglobinopathies.

Procedure

In a cross-sectional study, patients aged 12–50 years, treated in Germany, Austria, or Switzerland, were surveyed on fertility-related aspects. Medical data, including fertility testing results, were collected from patient records.

Results

Overall, 116/121 eligible patients, diagnosed with sickle cell disease (70.7%), thalassemia (27.6%), or other hemoglobinopathy (1.7%), participated in our study (57.8% female, median age 17.0 years, range 12–50 years). All participants required treatment of the underlying hemoglobinopathy: 68.1% received hydroxyurea, 25.9% required regular blood transfusions, and 6.0% underwent hematopoietic stem cell transplantation (HSCT). Most patients (82/108, 75.9%) stated a considerable to strong desire for (future) parenthood, independent of sex, education, diagnosis, or subjective health status. Fertility counseling was only recalled by 32/111 patients (28.8%) and least frequently by younger patients (12–16 years) or those treated with regular blood transfusions or hydroxyurea. While fertility testing was documented for 59.5% (69/116) in medical records, only 11.6% (13/112) recalled previous assessments. FP was only used by 5.4% (6/111) of patients.

Conclusion

Most patients with hemoglobinopathies wish to have biological children, yet only few recalled fertility counseling and testing. Adequate patient counseling should be offered to all patients at risk for infertility.     

Unrelated cord blood transplantation for second hemopoietic stem cell transplantation

BACKGROUND: The Kanagawa Cord Blood Bank (KCBB) reports the treatment of 12 patients who received umbilical cord blood transplantation (CBT) from unrelated donors as their second hemopoietic stem cell transplantation (HSCT). METHODS: Provided by the KCBB, between February 1997 and September 2000, 12 patients had unrelated CBT as a second HSCT. Six patients were male and six female; nine patients were in malignant, and three were in non-malignant conditions. The median age of the patients was 7.9 years (range, 2.2-28.0), and the median bodyweight was 22.5 kg (12.0-55.0). The HLA-A and -B serological and DR genotypical disparities between the patients and CBT donors were as follows: one patient was a 0-mismatch, six were 1-mismatches, and five were 2-mismatches. RESULTS: The median time between first and second HSCT was 14.0 months (1.0-47.0). The overall survival rate was 25.0%, three years after CBT (Kaplan-Meier estimate). Mortality after CBT as a second HSCT accounted for nine cases, six from infection and three from treatment-related mortality other than infection. CONCLUSION: Cord blood transplantation offers the advantage of rapid availability, absence of donor risk, and possibly less HLA restriction. In these contexts, unrelated CBT should be considered as a source of HSCT for a second transplant.     

Outcome of hematopoietic stem cell transplantation of children with very high risk acute lymphoblastic leukemia in first complete remission

Schechter T, Ishaqi KM, Rojas M, Irina Z, Doyle JJ, Gassas A. Outcome of hematopoietic stem cell transplantation of children with very high risk acute lymphoblastic leukemia in first complete remission.
Pediatr Transplantation 2010:14: 377–382. © 2009 John Wiley & Sons A/S. Abstract: Approximately 10% of children with ALL present at diagnosis with VHR for relapse if treated with chemotherapy alone. They may benefit from allogeneic HSCT in CR1. We have reviewed the outcome of this population in our institution. Forty‐three patients (median age: 8.9 yr) with VHR ALL in CR1 underwent HSCT from October 1994 to April 2006. VHR features included Philadelphia chromosome (n = 17), induction failure (n = 9), hypodiploidy (n = 6), MLL gene rearrangement (n = 5), and others (n = 6). All patients received TBI (1200 cGy) with either CY and/or etoposide. Stem cell source was unrelated (n = 24) and related (n = 19). Incidence of grade III‐IV acute GVHD and chronic extensive GVHD were 25% and 16%, respectively. Twelve patients relapsed (eight received related HSCT). Eleven patients died due to transplant‐related mortality (eight received unrelated HSCT). For a median follow up of 39 months (range 11–110), the event free survival and OS were 0.49 (95% CI: 0.31–0.67) and 0.53 (CI: 0.44–0.71), respectively. Outcomes of children with VHR ALL receiving HSCT in CR1 remain unsatisfactory. Relapse, mainly after related HSCT, and TRM, mainly after unrelated HSCT, continue to be major problems.     

Osteosarcoma After Hematopoietic Stem Cell Transplantation in Children and Adolescents: Case Report and Review of the Literature

Osteosarcoma as a secondary malignancy after hematopoietic stem cell transplantation (HSCT) is very rare. We present a case and review of 18 other cases reported to date. Our patient underwent HSCT for myelodysplastic syndrome at the age of 4 years. She developed osteosarcoma 13 years later. She underwent surgery after three courses of neoadjuvant chemotherapy followed by chemotherapy and mifamurtide. She has no evidence of disease 28 months after termination of chemotherapy. In 18 other cases of secondary osteosarcoma in the literature, 15 had received total body irradiation, eight had received alkylating agents, and six had received etoposide. The median interval from HSCT to the onset of osteosarcoma was 6.5 years (range 2.5–15.3), which confirms that children undergoing HSCT should be followed up for many years. In conclusion, osteosarcoma must be included in the differential diagnosis among solid tumors that may develop following HSCT.     

Nocturnal haemoglobin oxygen saturation variability is associated with vitamin C deficiency in Tanzanian children with sickle cell anaemia

Aim: To compare pulse oximetry in children with sickle cell anaemia (SCA) and controls and test the hypothesis that vitamin C deficiency (VCD; <11.4 μmol/L) is associated with nocturnal haemoglobin oxygen desaturation in SCA. Methods: We undertook nocturnal and daytime pulse oximetry in 23 children with SCA (median age 8 years) with known steady‐state plasma vitamin C concentrations and 18 siblings (median 7 years). Results: Median nocturnal delta 12 s index (delta12 s), a measure of haemoglobin oxygen saturation (SpO₂) variability, was 0.38 (interquartile range 0.28–0.51) in SCA and 0.35 (0.23–0.48) in controls, with 9/23 and 6/18, respectively, having a delta12 s >0.4, compatible with obstructive sleep apnoea (OSA). Eleven of twenty‐three with SCA had VCD; logged vitamin C concentrations showed a 66% decrease per 0.1 unit increase in delta12 s ([95% CI ?86%, ?15%]; p = 0.023) and delta12 s >0.4 was associated with VCD (odds ratio 8.75 [1.24–61.7], p = 0.029). Daytime and mean nocturnal SpO₂ were lower in SCA but there was no association with vitamin C. Conclusion: Obstructive sleep apnoea (OSA), detected from nocturnal haemoglobin oxygen saturation variability, is common in Tanzanian children and associated with vitamin C Deficiency in SCA. The direction of causality could be determined by comparing OSA treatment with vitamin C supplementation.     

Effect of hydroxyurea on physical fitness indices in children with sickle cell anemia

The current studies aimed at determining physical fitness indices and anthropometrics profiles of children with sickle cell anemia (SCA) after the use of hydroxyurea (HU). Ninety-three male schoolchildren--who participated previously in a similar study before the introduction of HU--comprising 2 groups participated in the studies. Group 1 was 41 children who were suffering from sickle cell disease (SCD) and were on HU for a minimum of 2 years, whereas group 2 was 50 normal healthy controls. Anthropometrics measurement and parameters of physical fitness were assessed in all subjects. All children were also subjected to a minimum of 6-minute running exercise test on a flat motorized treadmill at speed corresponding to 5 km/h. Throughout the test heart rate was monitored and recorded during exercise and for 10 minutes during recovery. Blood hemoglobin (Hb) and HbF% were measured after the use of HU. The mean values of weight, height, and lean body mass were still lower in the SCD children (P < .05) compared with the healthy subjects. However, they had significant decrease in the mean heart rate values and they spent longer time on the treadmill before they got tired compared to their previous performance and were just below the normal controls. Hydroxyurea treatment improved the aerobic exercise tolerance and most of the physical fitness parameters in children with SCD.     

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IS SUPERIOR TO IMMUNOSUPPRESSIVE THERAPY IN INDIAN CHILDREN WITH APLASTIC ANEMIA—A SINGLE-CENTER ANALYSIS OF 100 PATIENTS

The authors compared the outcome in 100 children (61 boys, 39 girls; median age of 10.1 ± 3.4 years) with aplastic anemia who underwent either immunosuppressive therapy (IST; n = 70) or hematopoietic stem cell transplantation (HSCT; n = 30) between 1998 and 2007. Conditioning regimes for HSCT were a combination of either cyclophosphamide (Cy) with antilymphocyte globulin (ALG) or fludarabine (Flu) with Cy or busulfan (Bu) ± antithymocyte globulin (ATG). Stem cell source was bone marrow in 20 and peripheral blood stem cells (PBSCs) in 10. Patients undergoing IST received either equine ALG or ATG in combination with steroids and cyclosporine. Primary engraftment was seen in 25 children (83.3%), with acute graft-versus-host disease (aGvHD) in 5 (16.6%). The day 100 transplant-related mortality (TRM) was 30% and at a median follow up of 36 months (range: 6–197), the overall and disease-free survival is 70%. Among children who received IST, 60 children received ALG while 10 received ATGAM. Responses were seen in 27 children (43.5%), which was complete (CR) in 12 and partial (PR) in 15. At a median follow up of 38 months (range: 1–84), the overall survival is 37.1%, with 81.4% survival among responders and <10% survival among non-responders. HSCT would be the treatment of choice in children with severe aplastic anemia who have a human leukocyte antigen (HLA)-matched related donor and is superior to IST in this series from India.     

儿童造血干细胞移植并发出血性膀胱炎的危险因素分析与防治研究

目的观察儿童造血干细胞移植（HSCT）中出血性膀胱炎（HC）的发病情况,探讨其发病危险因素和防治策略。方法回顾分析1998年10月—2004年6月本移植中心完成的53例儿童HSCT的临床资料,其中脐血移植（UCBT）37例,外周血造血干细胞移植（PBSCT）16例。HC的预防分为2组：（1）常规组（15例）,采用水化、碱化尿液、强力利尿和巯乙磺酸钠（Mesna）;（2）前列腺素E1（PGE1）组（38例）,在常规组的基础上加用PGE1。结果53例中发生HC11例（21％）,其中Ⅰ度2例（2／11,18％）,Ⅱ度4例（4／11,36％）,Ⅲ度5例（5／11,46％）;11例HC中,早发性4例（36％）,迟发性7例（64％）。HC发病时间为＋2d-＋25d（中位时间＋15d,移植后为“＋”）。15例常规预防组中发生HC2例（13％）,38例PGE1组中发生9例（24％,P〉0．05）。单因素分析显示,受者移植年龄≥6岁、预防移植物宿主病（GVHD）阳性、巨细胞病毒（CMV）感染组的HC发生率分别高于年龄〈6岁（32％vs8％,χ^2=4．68,P〈0．05）、GVHD阴性（35％vs7％,χ^2=5．96,P〈0．05）、CMV未感染组（62％vs 13％,χ^2=7．22,P〈0．05）。logistic回归分析表明,HC发病仅与年龄（OR=3．53,P〈0．05）和CMV感染（OR=4．31,P〈0．05）有显著的相关性。采用充分水化、碱化尿液、选择性输注血小板、抗病毒和尿道膀胱冲洗等综合性治疗,全部病例均获得治愈。结论受者移植年龄≥6岁和CMV感染是儿童HSCT并发HC的重要危险因素,PGE1不能降低HC的发生。儿童HSCT后HC预后多良好。     

Clinical complications in severe pediatric sickle cell disease and the impact of hydroxyurea

Background

More evidence of the safety and effectiveness of hydroxyurea (HU) in community‐based cohorts of pediatric patients with sickle cell disease (SCD) are needed. The association of HU with organ‐specific clinical complications and adverse events is examined herein.

Methods

Medicaid medical and pharmacy claims for the calendar years January 1996 through December 2006 were used to identify a cohort of children and adolescent patients (ages 17 and under) with a diagnosis of SCD (homozygous) who were treated with HU and developed disparate complications or adverse side effects. Of the 2,194 pediatric SCD patients identified, 175 (8%) were treated with HU. Incidence density matching (1 case: 2 controls) was used to select the control group on age, gender, ethnicity, time in the Medicaid data set, and baseline severity resulting in a total study cohort of 523 cases.

Results

Organ‐specific complications were more likely in the HU‐treated group compared to non‐HU‐treated group: cardiovascular complications (odds ratio [OR] = 3.15; confidence interval [CI] = 1.97–5.03); hepatic complications (OR 5.41; CI = 3.54–8.27); renal complications (OR 5.09; CI 3.37–7.67); and pulmonary complications (OR 4.07; CI 1.88–8.79). Many of these conditions began developing before HU was prescribed. Developing three or more complications was also more likely in the HU group (27.4% vs. 7.0%, P < 0.0001).

Conclusions

Extending previous findings to routine practice settings, HU is being administered to the most severely ill children with SCD, many of whom had already started to develop organ‐specific complications, but it is not associated with development of serious adverse events. Pediatr Blood Cancer. 2010;56:90–94. © 2010 Wiley‐Liss, Inc.     

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目的分析小儿造血干细胞移植(HSCT)后出血性膀胱炎(HC)的临床特点,探讨其发病危险因素。方法对1998年10月至2004年6月中山大学附属二院儿科完成的52例小儿HSCT后11例HC的临床资料进行回顾分析。结果11例HC中轻度(Ⅰ～Ⅱ度)6例,重度(Ⅲ～Ⅳ度)5例;早发性4例,迟发性7例;发病时间为术后+2d至+25d(中位数为+15d),病程3～60d(中位数为17d)。临床表现均有血尿,其中典型尿频、尿急、尿痛及肉眼血尿7例。HC患儿组中性粒细胞植入时间和血小板植入时间与非HC患儿组比较差异无显著性(P>0.05)。受者移植年龄≥6岁、aGVHD阳性、CMV感染组的HC发生率分别高于年龄<6岁(32.1%和8.3%,P<0.05)、GVHD阴性(34.6%和7.7%,P<0.05)、CMV未感染组(62.5%和13.6%,P<0.05)。结论小儿HSCT后HC有其自身的临床特征;受者移植年龄≥6岁、aGVHD阳性、CMV感染为其发生的危险因素。     

Metabolic syndrome as a late effect of childhood hematopoietic stem cell transplantation – A thorough statistical evaluation of putative risk factors

Background

Metabolic syndrome (MetS) is frequent among survivors of childhood hematopoietic stem-cell transplantation (HSCT), but assessment of risk factors is challenged by survivor and participation bias in long-term follow-up studies.

Methods

A cohort of 395 pediatric patients transplanted between 1980 and 2018 was investigated. MetS was assessed at follow-up between December 2018 and March 2020. Two composite outcomes ((a) combining MetS and death, (b) combining MetS, death, and nonparticipation) were considered to address the risk of selection bias.

Results

Among 234 survivors invited to the follow-up, 96 individuals (median age 27 years) participated. MetS prevalence was 30% among participants. The only significant HSCT risk factor was a variable combining HSCT indication and conditioning with total-body irradiation (TBI) (p = .0011). Compared to acute leukemias (AL) treated with high-grade TBI (8–12 Gy), a lower MetS prevalence was seen for nonmalignant diseases treated with no/low-grade TBI (0–4.5 Gy) (OR = 0.04, 95% confidence interval (CI): 0.00–0.23). Analyses of the composite outcomes indicated overestimation of the effect of high-grade TBI due to selection bias. Scrutiny showed strong residual confounding between HSCT indication and high-grade TBI within AL-patients. The HSCT effect on MetS reflected HSCT effects on high-density-lipoprotein (HDL) and triglycerides. Compared to AL treated with high-grade TBI, nonmalignant diagnoses treated with no/low-grade TBI had higher HDL (+40%, 95% CI: +21% to +62%) and lower triglyceride (−59%, 95% CI: −71% to −42%).

Conclusion

The TBI effect on MetS may be overestimated in follow-up studies due to selection bias and confounding. The TBI effect was confined to the potentially modifiable MetS criteria  HDL and triglyceride.     

Hematopoietic stem cell transplantation in patients with severe congenital neutropenia: An analysis of 18 Japanese cases

Oshima K, Hanada R, Kobayashi R, Kato K, Nagatoshi Y, Tabuchi K, Kato S; for the Hematopoietic Stem Cell Transplantation Committee of the Japanese Society of Pediatric Hematology. Hematopoietic stem cell transplantation in patients with severe congenital neutropenia: An analysis of 18 Japanese cases.
Pediatr Transplantation 2010: 14:657–663. © 2010 John Wiley & Sons A/S. Abstract: We studied the outcome of allogeneic HSCT in patients with SCN. Between 1989 and 2005, 18 patients with SCN in Japan received HSCT for reasons other than malignant transformation, i.e., because of the lack of or a partial response to treatment with r‐HuG‐CSF. The median age of the patients at the first HSCT was three and a half yr (range 0.2–16.7 yr). Nine patients received stem cells from an HLA‐identical sibling donor and nine from an alternative donor. Twelve and six patients received myeloablative and non‐myeloablative conditioning regimens, respectively. Engraftment occurred at the first HSCT in 12 patients, four patients received a second HSCT for graft failure, and two patients died. The cause of death was renal failure and graft failure at the first and second HSCT, respectively. The cumulative incidence of grade II–IV acute GVHD and TRM at the first transplantation was 11% and 5.6%, respectively. Of our patients, 16 are alive and in complete remission, with a median follow‐up of six and a half yr. Our results suggest that HSCT is beneficial for patients with SCN refractory to r‐HuG‐CSF treatment.     

Secondary benefit of maintaining normal transcranial Doppler velocities when using hydroxyurea for prevention of severe sickle cell anemia

In a retrospective cohort study, we tested the hypothesis that when prescribing hydroxyurea (HU) to children with sickle cell anemia (SCA) to prevent vaso‐occlusive events, there will be a secondary benefit of maintaining low transcranial Doppler (TCD) velocity, measured by imaging technique (TCDi). HU was prescribed for 90.9% (110 of 120) of children with SCA ≥5 years of age and followed for a median of 4.4 years, with 70% (n = 77) receiving at least one TCDi evaluation after starting HU. No child prescribed HU had a conditional or abnormal TCDi measurement. HU initiation for disease severity prevention decreases the prevalence of abnormal TCDi velocities.     

Plasma homocysteine levels and folate status in children with sickle cell anemia.

PURPOSE: A sensitive inverse relationship between plasma homocysteine concentration and folate status has been demonstrated. Although children with sickle cell anemia (SCA) are at potential risk for folate deficiency, plasma homocysteine levels have not been reported in such patients. Therefore, a study was designed to assess plasma homocysteine levels as a marker of folate status. DESIGN: Plasma homocysteine concentrations were measured in 120 children with SCA (102 in steady state and 18 during an acute complication) who had never received supplemental folic acid. Folate status was directly assessed in 34 of these patients. RESULTS: Plasma homocysteine levels in the patients with SCA and control subjects were similar. The mean value +/- 1 SD was 5.8+/-2.5 micromol/L (range, 1.6 to 14.1 micromol/L) in the patients with SCA and 6.1+/-2.7 micromol/L (range, 1.7 to 15.3 micromol/L) in 73 pediatric control subjects. In a subpopulation of the study group (34 children), simultaneous serum folate, red cell folate, and total homocysteine concentrations were also measured. Their serum folate and red cell folate concentrations were normal: 12.4+/-10.0 nmol/L (range, 1 to 42 nmol/L) and 604+/-374.7 nmol/L (range, 205 to 1741 nmol/L), respectively. There was no correlation of plasma homocysteine concentration with various clinical or laboratory measures or with red cell folate concentration. CONCLUSION: Folate stores in children with SCA not receiving folic acid supplements are adequate despite an underlying hemolytic anemia.     

Transplant‐related mortality following allogeneic hematopoeitic stem cell transplantation for pediatric acute lymphoblastic leukemia: 25‐year retrospective review

Background

Over the last 25 years, donor source, conditioning, graft‐versus‐host disease prevention and supportive care for children undergoing hematopoeitic stem cell transplantation (HSCT) have changed dramatically. HSCT indications for acute lymphoblastic leukemia (ALL) now include high‐risk patients in first and subsequent remission. There is a large burden of infectious and pre‐HSCT morbidities, due to myelosuppressive therapy required for remission induction. We hypothesized that, despite these trends, overall survival (OS) had increased.

Procedure

A retrospective audit of allogeneic pediatric HSCT for ALL was performed in our institution over 25 years. Outcomes for 136 HSCTs were analyzed in three consecutive 8‐year periods (Period 1: 1/1/1984–31/8/1992, Period 2: 1/9/1992–30/4/2001, Period 3: 1/5/2001–31/12/2009).

Results

Despite a significant increase in unrelated donor HSCT, event‐free and OS over 25 years improved significantly. (EFS 31.6–64.8%, P = 0.0027; OS 41.8–78.9%, P < 0.0001) Concurrently, TRM dropped from 33% to 5% (P = 0.0004) whilst relapse rate was static (P = 0.07). TRM reduced significantly for matched sibling and unrelated cord blood transplantation (UCT) in Period 3 compared with earlier periods (P = 0.036, P = 0.0098, respectively). Factors leading to improved survival in patients undergoing UCT include better matching, higher total nucleated cell doses, and significantly faster neutrophil engraftment. Length of initial HSCT admission was similar over time.

Conclusion

EFS and OS have increased significantly despite heightened HSCT complexity. This survival gain was due to TRM reduction. Contemporary patients have benefited from refined donor selection and improved supportive care. Overall rates of leukemic relapse post‐HSCT are unchanged, and remain the focus for improvement. Pediatr Blood Cancer 2013;160:1520–1527. © 2013 Wiley Periodicals, Inc.     

异基因造血干细胞移植治疗儿童范可尼贫血5例并文献复习

目的初步探讨异基因造血干细胞移植(HSCT)治疗范可尼贫血(FA)的疗效,为探索更加优化移植方案提供依据。方法回顾性分析2012年6月-2016年12月我院收治5例FA患儿进行HSCT的临床资料并复习相关文献。5例患儿中2例行非血缘相合HSCT治疗,3例行单倍体HSCT治疗。预处理方案以氟达拉滨(Flu)、低剂量环磷酰胺(CTX)、抗人胸腺/T淋巴细胞免疫球蛋白(ATG-G/F)为主干,根据移植前输血总量、是否合并白血病,在主干基础上±白消安(Bu)或±全身照射(TBI)。5例患儿回输CD34~+细胞中位计数为8.46(5.46~15.29)×10~6/kg,单个核细胞(MNC)中位计数为13.07(8.33~14.26)×10~8/kg。采用他克莫司和吗替麦考酚酯联合预防移植物抗宿主病(GVHD)。随访中位时间40.7(15~42)个月。结果 5例患儿HSCT预处理过程中,除1例合并严重消化道黏膜反应,其余耐受性尚可;中性粒细胞恢复中位时间10(8~13)d,血小板恢复中位时间16(12~61)d,无原发性植入失败发生;移植后3例发生移植物排斥,分别通过停用全部免疫抑制剂、回输供者干细胞后恢复为完全供者型;4例发生不同程度急性GVHD,3例需升级为二线免疫抑制治疗控制病情,2例发展为慢性GVHD;随访至2016年12月,2例无事件存活,2例存在慢性GVHD,目前病情控制理想,1例死亡。4例存活患儿移植后血细胞未再检测出FA相关基因突变,生长发育同正常同龄儿童,目前尚未发现合并实体肿瘤。结论对于缺乏同胞相合供者的FA患者,其他类型HSCT治疗采用"Flu+低剂量CTX+ATG±Bu或±TBI"预处理方案耐受性尚可,无原发性植入失败发生,但加用Bu或TBI对预处理相关毒性及远期预后的影响还需要深入研究;移植物排斥和GVHD仍是影响患儿生存主要因素,探索个体化、优化HSCT方案治疗FA的临床研究已成为必然。     

Outcomes of children,adolescents, and young adults following allogeneic stem cell transplantation for secondary acute myeloid leukemia and myelodysplastic syndromes—The MD Anderson Cancer Center experience

We conducted a retrospective analysis of outcomes for children and young adults with sAML/sMDS who underwent HSCT at our institution. Thirty‐two patients (median age 20 years) with sAML (n=24) and sMDS (n=8) received HSCT between 1990 and 2013. The median time from sAML/sMDS diagnosis to HSCT was 4.1 months (range: 1.2‐27.2 months). The transplant regimens were primarily busulfan based (n=19). BM was the primary donor source (n=15). Eleven recipients were transplanted with residual disease. At a median follow‐up of 62.3 months (range: 0.4‐250.9 months), 14 patients had disease recurrence. Acute GVHD, grade III/IV, occurred in three patients. Causes of death were as follows: disease relapse (n=12), infection (n=2), pneumonia (n=1), pulmonary hemorrhage (n=1), acute GVHD (n=1), and graft failure (n=1). A PS of ≥90% at the time of HSCT had a significant impact on PFS (P=.02). Patients achieving pretransplant primary CR (n=8) and those with sMDS and RA (n=6) had prolonged PFS (P=.04). On multivariate analysis, shorter time to transplantation (≤6 months from diagnosis of sAML/sMDS) was associated with superior OS (P=.0018) and PFS (P=.0005).     

Concentrations of adipokines in children before and after hematopoietic stem cell transplantation

Adipokines have multiple effects, including regulation of glucose metabolism, cell proliferation, inflammation, and angiogenesis. The aim of the study was to determine plasma concentrations of adiponectin, apelin, leptin, and resistin as well as soluble leptin receptor in pediatric hematopoietic stem cell transplantation (HSCT). The expression of genes encoding the studied peptides was measured using microarray technique. Plasma concentrations of tested peptides were measured before and after oral glucose tolerance test in children treated with HSCT (n = 38) and in healthy controls (n = 26). The peptides were measured before HSCT (pre-HSCT group; n = 38) and after a median of 6 months after HSCT (post-HSCT group; n = 27 of 38 children treated with HSCT). In addition, measurements of fasting plasma glucose, insulin, lipids, and high-sensitivity C-reactive protein (hsCRP) were performed. In both HSCT groups, atherogenic lipid profile, low-grade systemic inflammation was observed. Leptin, adiponectin, and resistin also appear to be good markers of disease burden and low-grade systemic inflammation. Adipokines may be good markers of disease burden and may influence metabolic complications of HSCT. Future studies on larger groups of patients will explain if changes of the concentrations of leptin, adiponectin, and apelin observed in our study and confirmed by expression levels influence engraftment and reconstitution of cell lines.     

Haematopoietic stem cell transplantation in 12 patients with cerebral X-linked adrenoleukodystrophy

In an attempt to elucidate prognostic factors, the data on 12 boys who underwent haematopoietic stem cell transplantation (HSCT) for cerebral X-linked adrenoleukodystrophy were evaluated. Two further patients received HSCT but died from transplantation-related complications. The data included neurological examination, neuropsychological testing and magnetic resonance imaging (MRI). Follow-up after HSCT was up to 5.5 years. Six patients showed a moderate to severe clinical deterioration after HSCT including two who died within 6 months. In this group, a MRI severity score of 10 or higher before HSCT was associated with severe impairment and a score of more than 12 was followed by rapid deterioration and death after HSCT. The presence of neurological symptoms before HSCT also affected prognosis. Six patients showed no deterioration in neurological or neuropsychological assessment after HSCT. CONCLUSION: our data confirm that haematopoietic stem cell transplantation can stop the progress of demyelination when performed at a critical early stage of the disease. The prognosis in an individual patient for the clinical course after stem cell transplantation can in general be given based on the status before transplantation, although individual patients may show an unexpected course.