Monitoring of inosine monophosphate dehydrogenase activity in mononuclear cells of children with acute lymphoblastic leukemia: enzymological and clinical aspects

BACKGROUND: Inosine 5'-monophosphate dehydrogenase (IMPDH; EC1.1.1.205) catalyzes the rate-limiting step in guanine nucleotide biosynthesis, and may play an important role in treatment of patients with antipurines. METHODS: We used an HPLC method to measure the IMPDH activity in peripheral blood and bone marrow mononuclear cells (MNC). IMPDH activities were determined in children who were diagnosed with and treated for acute lymphoblastic leukemia (ALL), and in a group of control children. RESULTS: The median IMPDH activity for control children was 350 pmol/10(6) pMNC/hr (range 97-896; n = 47). No gender or age differences were observed. IMPDH activity at diagnosis of ALL was correlated with the percentage of peripheral blood lymphoblasts (r = 0.474; P < 0.001; n = 71). The median IMPDH activity at diagnosis was 410 pmol/10(6) pMNC/hr (range 40-2009; n = 76), significantly higher than for controls (P = 0.012). IMPDH activity significantly decreased after induction treatment, and during treatment with methotrexate (MTX) infusions (median 174 pmol/10(6) pMNC/hr; range 52-516; n = 21). The activity remained low during maintenance treatment with 6-mercaptopurine (6MP) and MTX, at a significantly lower level than for controls (P < 0.004). One year after cessation of treatment IMPDH activity returned to normal values. CONCLUSION: The decrease of IMPDH activity at remission of ALL seems to be at least partly due to the eradication of lymphoblasts with the type 2 isoform of the enzyme.     

脐血移植治疗重型β地中海贫血的临床研究

目的探讨脐血移植(UCBT)治疗重型β-地中海贫血(简称β-地贫)的疗效.方法用人类白细胞抗原(HLA) 全相合或不全相合UCBT治疗重型β-地贫患儿12例.供受者的有核细胞(3.63～16.0)×107/kg,CD34+细胞(0.11～1.03)×106/kg,粒-巨噬细胞集落形成单位(0.17～1.18)×105/kg.移植的预处理方案HLA全相合的患儿采用马利兰+环磷酰胺+抗胸腺细胞球蛋白方案;HLA 2个位点不全相合者采用高剂量输血+连续静脉滴注去铁胺+羟基脲+氟达拉宾+马利兰+环磷酰胺+抗胸腺细胞球蛋白方案.结果 10例患儿获得植入,其中7例为长期稳定植入,3例植入后发生排斥;2例未能植入.获得植入的10例患儿均发生急性移植物抗宿主病(aGVHD),其中Ⅰ度aGVHD 7例,Ⅱ度aGVHD 3例.脱离地贫状态生存7例,血红蛋白始终维持正常.3例恢复地贫状态.2例未获植入的患儿1例发生移植后再生障碍性贫血,1例死于严重感染.结论 UCBT是目前β-地贫最有效的治疗手段.     

Allogeneic bone marrow transplantation in children with chronic myelogenous leukemia

PURPOSE: To determine the outcome of children undergoing allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML) at the authors' institution. PATIENTS AND METHODS: Between 1985 and 1999, 18 allogeneic bone marrow transplantations were performed in 17 patients with CML at the Hospital for Sick Children in Toronto. Median age at diagnosis was 9.5 years (range 3-17). Fourteen patients had disease in the first chronic phase, one had disease in the second chronic phase, and two had disease in the accelerated phase. Preparative regimens varied, with radiation-based protocols used in eight patients. Thirteen donors were related (11 matched, 2 mismatched); four were unrelated (2 matched, 2 mismatched). Patients received T-cell-replete bone marrow a median of 7.5 months (range 2.2-22) from diagnosis. A median of 3.0 x 10(8)/kg nucleated cells was infused (range 1.6-6.7). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in 13 children. cyclosporine in three, and methotrexate in one. RESULTS: Primary graft failure occurred in one patient. Grade 2 acute GVHD or more developed in 11 of the 17 children (64%; grade 2 in 4, grade 3 in 7). Chronic GVHD occurred in 6 of the 16 patients at risk (37.5%; 5 extensive, 1 localized). No patient experienced overt or cytogenetic relapse. There were two deaths (12%): one from acute GVHD and cytomegalovirus pneumonia and the other from chronic GVHD. Probability of 5-year event-free survival was 87 +/- 9%. CONCLUSIONS: These results strongly support the practice of allotransplantation in children with CML, even in the setting of advanced disease and histoincompatibility. Efforts should be aimed at reducing the transplantation-related death rate.     

Umbilical cord blood transplantation in Chinese children with beta-thalassemia

To evaluate factors affecting outcome of sibling umbilical cord blood transplantation in Chinese children with thalassemia. The authors conducted a retrospective review of all patients undergoing such transplants in a single institution. Nine children with thalassemia major were diagnosed at a median age of 12 months. They received irregular blood transfusions and suboptimal iron chelation therapy before transplant. Sibling cord blood transplant was performed at a median of 5.5 years (range 3.5-10 years). Six donors were HLA-identical; three were one- to three-antigen mismatched. The mean number of nucleated cells infused was 6.6 x 10(7)/kg (range 3.4-12.7); the mean number of CD34+ cells infused was 3.8 x 10(5)kg (range 0.6-11.7). Seven patients had engraftment of donor cells. The median number of days to achieve a neutrophil count of > 0.5 x 10(9)/L was 19 days (range 10-25); the median number of days to achieve a platelet count of > 20 x 10(9)/L was 33 days (range 19-63). Of the six patients who received HLA-identical transplants, one developed grade 2 and two developed grade 1 acute graft-versus-host disease. Two of the three patients receiving mismatched cord blood did not achieve engraftment, and the other one engrafted but developed grade 4 acute graft-versus-host disease. Two patients subsequently developed secondary graft rejection and had autologous marrow regeneration before day 60 posttransplantation. With a median follow-up of 49 months (range 38-64), eight patients survived but only four were transfusion-independent. Umbilical cord blood transplant appears to have a higher chance of nonengraftment and secondary rejection. A more intensive immunosuppressive conditioning regimen may be required.     

Systemic methotrexate exposure is greater after intrathecal than after oral administration

PURPOSE: To compare systemic exposure after intrathecal and oral methotrexate administration. PATIENTS AND METHODS: We analyzed red cell methotrexate polyglutamate concentrations with a sensitive radioligand-binding assay in 80 patients enrolled in the Children's Cancer Group (CCG) trial 1922 for acute lymphoblastic leukemia. Methotrexate concentrations were measured 7 days after the last doses of intrathecal and oral routes, using patients as their own controls. Intrathecal methotrexate was given on an age-adjusted schedule. Data was normalized to the actual dose received per body surface area. RESULTS: The mean red cell methotrexate concentration 7 days after the last of four weekly intrathecal doses of methotrexate was 178 pmol/mL red blood cells, which was significantly greater than the result 7 days after subsequent weekly oral methotrexate of 122 pmol/mL (P = 0.00001). Intrathecal dosing resulted in an average systemic exposure ratio of 1.7 to 1 compared with oral administration. CONCLUSION: Intrathecal methotrexate administration results in significantly greater systemic exposure than oral administration. Our data support the hypothesis that the systemic effect of intrathecal methotrexate affects ALL therapy.     

Acute lymphoblastic leukemia in a developing country: preliminary results of a nonrandomized clinical trial in El Salvador

PURPOSE: To improve outcome and study biology of childhood acute lymphoblastic leukemia (ALL) in El Salvador. PATIENTS AND METHODS: Between January 1994 and December 1996, 153 children of El Salvador had newly diagnosed ALL treated in a collaborative program between Hospital Benjamin Bloom and St. Jude Children's Research Hospital (SJCRH). Therapy was based on a modified SJCRH protocol, with uniform remission induction (prednisone, vincristine, L-asparaginase) followed-up by consolidation with teniposide/cytarabine and/or high-dose methotrexate. Continuation treatment was risk-stratified: 123 patients assigned to the high-risk group received weekly rotational drug pairs, and 16 assigned to the standard-risk group received daily 6-mercaptopurine, weekly methotrexate, and monthly pulses of vincristine plus dexamethasone. High risk was defined as: DNA index < 1.16, age 12 months or younger, white blood cell count > or = 50 x 10(9)/L, T-cell immunophenotype, anterior mediastinal mass, central nervous system leukemia at diagnosis, or t(4;11), t(1;19), or t(9;22). Duration of the continuation treatment was 2.5 years in both groups. The median age at diagnosis of all patients was 4.8 (range I d-17 yrs), median leukocyte count was 15 (range 1-766) x 10(9)/L, and sex distribution was equal. RESULTS: Immunophenotypes were early beta-progenitor in 79%, T-cell in 3.9%, and inconclusive in 17% of cases. DNA index was <1.16 in 80.5% and was > or = 1.16 in 19.5% of the 123 known cases. For the analyzes, patients who refused therapy (abandoned treatment) were considered to have treatment failure as of their last follow-up dates. Complete remission was achieved in 126 of 151 (82.4%) patients (11 abandoned therapy during induction). The overall 4-year event-free survival (EFS) rate +/- 1 standard error was 48 +/- 6%. The 4-year EFS rates in patients at high-risk and standard-risk were 46 +/- 7% (n = 121) and 69 +/- 15% (n = 16), respectively (P = 0.20). When patients who refused further treatment are censored, the corresponding 4-year estimates of EFS are 51 +/- 8% and 75 +/- 14%, respectively. CONCLUSIONS: These results suggest that the biology of childhood ALL in El Salvador appears to be similar to that seen in the United States. Risk-directed chemotherapy can successfully be used in developing countries, but risk factors must be carefully determined and applied.     

The bioavailability of oral methotrexate in children with inflammatory bowel disease

OBJECTIVES: Methotrexate is used to treat patients with inflammatory bowel disease. Although no available pharmacologic data support the assumption that the bioavailability of methotrexate is diminished in patients with inflammatory bowel disease, most such patients receive methotrexate parenterally. METHODS: The oral bioavailability of methotrexate was determined in 11 pediatric patients being treated with methotrexate for inflammatory bowel disease. Serial plasma methotrexate concentrations were determined after equal subcutaneous and oral doses of methotrexate. RESULTS: The mean bioavailability of methotrexate in patients with inflammatory bowel disease was 84% +/- 38%. Interpatient variability in drug exposure was similar after oral and subcutaneous administration. CONCLUSIONS: The bioavailability of methotrexate in patients with inflammatory bowel disease is no different from that observed in other disease states. Subcutaneous administration of methotrexate does not appear to decrease the interpatient variability in drug exposure. There is no sound pharmacologic basis for favoring administration of methotrexate via the subcutaneous route for patients with inflammatory bowel disease.     

The effect of dexamethasone upon platelets and neutrophils of preterm infants with chronic lung disease

The effect of a 21-day (reducing dose) course of dexamethasone upon platelet numbers, neutrophil numbers and neutrophil morphology in ventilator-dependent preterm infants with chronic lung disease is reported. Forty-one infants, who were sepsis-free throughout the treatment period, received 46 courses of dexamethasone. In these infants the circulating platelet count increased significantly from 235 +/- 157 to 476 +/- 208 X 10(9)/L. Both total neutrophil numbers (7.94 +/- 7.16 to 19.56 +/- 12.40 X 10(9)/L) and immature neutrophil numbers (1.19 +/- 1.22 to 2.68 +/- 2.58 X 10(9)/L) also showed a significant increase reaching a peak on day 7 of treatment and decreasing thereafter. The immature:total (I:T) neutrophil ratio remained essentially unchanged. Eight other infants who developed serious sepsis during the treatment period showed a fall in both platelets (293 +/- 236 to 140 +/- 170 X 10(9)/L) and total neutrophil numbers (18.61 +/- 10.83 to 15.76 +/- 10.53 X 10(9)/L), together with an increase in immature neutrophils (2.30 +/- 2.80 to 8.22 +/- 13.91 X 10(9)/L) and consequent increase in I:T ratio.     

Preliminary results of propranolol treatment for patients with infantile hemangioma

Propranolol, a non-selective beta-blocker, has recently been introduced as a treatment for infantile hemangiomas. In this study, we evaluated the effect of propranolol in 12 infants with hemangioma. Twelve infants (9 girls) with a median age of 4.5 months were included in the study. All of the patients in the study group received short-term (1-9 weeks, median: 4 weeks) systemic corticosteroids as a first-line therapy. All patients received propranolol 2 mg/kg/day, divided into three doses. They were treated in an inpatient setting for the first 72 hours of the treatment. Vital signs, blood pressure and blood glucose were monitored. Propranolol treatment was given for 4-9 months (median: 5 months). In the study group, regression rate of the mean dimension of the lesion was 38% +/- 15 (range 15%-50, median 45%) at the 2nd month of therapy. Over 9 months, which was the maximum follow-up period, the regression rate of the mean dimension of the lesion was 55% +/- 31 (range 20%-80, median 50%). One patient had transient bradycardia, which improved spontaneously. No other side effect was observed in the study population. Propranolol appears to be an effective drug for infantile hemangiomas with good clinical tolerance. We suggest that propranolol is the preferable drug as the first-line therapy for infantile hemangiomas.     

Feasibility study of IL-11 and granulocyte colony-stimulating factor after myelosuppressive chemotherapy to mobilize peripheral blood stem cells from heavily pretreated patients

PURPOSE: Pediatric patients with solid tumors treated with prolonged dose-intensive chemoradiotherapy are poor mobilizers of peripheral blood stem cells (PBSC). We have conducted a pilot study to mobilize PBSC in eight pediatric patients with relapsed solid tumors using ifosfamide, carboplatin, and etoposide (ICE) followed-up by IL-11 plus granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS: Patients received ifosfamide 1.8 g/m2 per day for 5 days, carboplatin 400 mg/m2 per day for 2 days, and etoposide 100 mg/m2 per day for 5 days. After completion of ICE chemotherapy, patients received daily subcutaneous injections of G-CSF (5 microg/kg per day) and IL-11 (50-100 microg/kg per day) until peripheral stem cell apheresis. RESULTS: The median age was 11 years. Diagnosis included three relapsed Hodgkin disease, three relapsed central nervous system tumors, one relapsed Wilms tumor, and one relapsed rhabdomyosarcoma. The median number of apheresis procedures required to obtain 5 x 10(6) CD34+ cells/kg was one. The mean +/- standard error of mean (SEM) total CD34+ cells collected was 14.0+/-2.7 x 10(6)/kg. The mean +/- SEM total CD34+/CD41+ cells collected was 4.6+/-1.9 x 10(6)/kg. Seven of the eight patients have subsequently undergone myeloablative chemotherapy with autologous PBSC transplantation and have reconstituted hematopoiesis with a median time to neutrophil recovery of 10 days and platelet recovery of 15.5 days. CONCLUSIONS: We conclude that the regimen of ICE/IL-11 plus G-CSF is successful in mobilizing large numbers of CD34+ PBSC cells with a limited number (one) of apheresis collections in patients that have previously been heavily pretreated with chemotherapy/radiotherapy.     

Neuroblastoma in adolescents and adults: the Memorial Sloan-Kettering experience

BACKGROUND: We reviewed the utility of different treatment modalities in a large series of adolescents/adults with neuroblastoma (NB). PROCEDURE: The 30 adolescents/adults (median age, 19 years) had stage 2B (n = 1), 3 (n = 2), or 4 (n = 27) NB. Treatments included conventional and myeloablative therapy; local radiotherapy (RT); immunotherapy with anti-G(D2) 3F8 monoclonal antibody +/- granulocyte-macrophage colony-stimulating factor (GM-CSF); and 3F8 alternating with low-dose oral etoposide. RESULTS: Seven patients are in first (n = 4) or second (n = 3) complete/very good partial remission (CR/VGPR) at 9+ to 181+ (median, 45+) months. Among 13 newly diagnosed or minimally prior-treated patients, no major responses were seen in 4/4 treated with N4/N5 chemotherapy, but 6/9 treated with the higher dose N6/N7 regimens and surgery had major responses, and immunotherapy produced CR in BM in three patients. Among 17 patients referred because of resistant NB, favorable responses occurred in 6/12 treated with high-dose cyclophosphamide-based salvage therapy, including one patient who is in CR 170+ months after myeloablative consolidation and five patients who achieved CR/VGPR after 3F8/GM-CSF (n = 4) or 3F8/oral etoposide (n = 1). With a median follow-up of 32+ months post-RT, no local relapses occurred in 10/10 patients who received hyperfractionated 21 Gy RT to prevent regrowth of soft tissue masses that had been resected. CONCLUSIONS: High-dose chemotherapy and surgery can achieve a minimal disease state in >50% of newly diagnosed older NB patients. In that setting, local RT, and the use of agents with recently confirmed anti-NB activity, including anti-G(D2) antibodies, and cis-retinoic acid, may improve the poor prognosis of these patients reported to date.     

Cotransplantation of allogeneic mesenchymal and hematopoietic stem cells in children with aplastic anemia

We report here the preliminary results of allogeneic hematopoietic stem cell transplantation with mesenchymal stem cells (MSCs) for 6 cases of severe aplastic anemia. The patients ranged in age from 3 to 16 years, and the median time from diagnosis to transplantation was 32 months (range: 3-156 months). The conditioning regimens consisted of fludarabine, cyclophosphamide, and antithymocyte globulin with or without busulfan. Graft-versus-host disease (GvHD) was prevented by the administration of cyclosporine A, methotrexate, and mycophenolate mofetil, with or without anti-CD25 monoclonal antibody. The grafts were granulocyte colony-stimulating factor-mobilized bone marrow and peripheral blood from HLA antigen-haploidentical donors (3 cases) or peripheral blood only from unrelated HLA antigen-identical donors (3 cases). MSCs were intravenously injected at a median dose of 1.43 × 10(6)/kg (range: 0.85-2.5 × 10(6)/kg). The mean time for neutrophil and platelet recovery was 12.3 and 13.8 days, respectively. Acute GvHD grade I and II developed in 2 cases, and no chronic GvHD was documented. All patients were alive and transfusion independent at a median follow-up of 15 months (range: 6-29 months). Our report suggests that cotransplantation of allogeneic hematopoietic stem cells and MSCs might provide an opportunity for therapy for children with severe aplastic anemia.     

Hyperglycemia and hypoinsulinemia in patients with Fanconi-Bickel syndrome

Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by the combination of hepatorenal glycogen accumulation and Fanconi-type nephropathy. Mutations in GLUT2, the gene for facilitative glucose transporter protein 2 (GLUT2), cause FBS. AIM: To evaluate glucose and insulin responses to oral glucose load in patients with FBS. METHODS: Ten children (7.3 +/- 4.8 years) diagnosed with FBS in early infancy underwent a standard oral glucose tolerance test (OGTT); plasma glucose (PG) and serum insulin concentrations were measured at 30-min intervals for 2 hours. HbA1c, insulin-like growth factor-I, and fasting lipid profiles were also measured. RESULTS: Mean fasting and 2-h PG concentrations were 3.8 +/- 0.9 mmol/l and 8.6 +/- 3.0 mmol/1, respectively. 2-hour PG levels were above 11.1 mmol/l in two patients (20%) and between 7.75 and 11.1 mmol/ in four patients (40%). HbA1c was normal in all the patients with a mean of 5.4 +/- 0.3%. Mean fasting and peak serum insulin levels were 8.7 +/- 0.8 pmol/ and 98.6 +/- 43.0 pmol/l, respectively, and did not differ between the patients with normal and abnormal OGTT. Patients with abnormal OGTT were younger (4.8 +/- 3.2 vs 11.0 +/- 4.8 yr; p = 0.04). Fasting PG increased with age (r = 0.80, p < 0.01). Total and LDL cholesterol as well as triglyceride concentrations were elevated. CONCLUSIONS: Most but not all patients with FBS have impaired glucose tolerance/diabetes range hyperglycemia after OGTT while maintaining normal HbA1c. Patients with FBS are relatively hypoinsulinemic. Both fasting hypoglycemia and post-OGTT hyperglycemia seem to improve with age.     

High-dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia: St. Jude Total Therapy Study X

High-dose methotrexate (HDMTX, 1,000 mg/m2) and cranial irradiation/sequential chemotherapy (RTSC) were compared for ability to extend complete remission durations in children with acute lymphoblastic leukemia (ALL). Three hundred thirty patients were enrolled in the study, according to our criteria for standard-risk ALL: a leukocyte count less than 100 X 10(9)/L, no mediastinal mass, no leukemic involvement of the central nervous system (CNS), and blast cells lacking sheep erythrocyte receptors and surface immunoglobulin. Prednisone-vincristine-asparaginase induced complete remissions in 95% of the patients, who were then randomized to receive either HDMTX (n = 154) or RTSC (n = 155). HDMTX was administered with intrathecal MTX for the first 3 weeks following remission induction, and then every 6 weeks with daily mercaptopurine (MP) and weekly oral MTX for a total of 18 months. The RTSC regimen consisted of 1,800 cGy cranial irradiation and intrathecal MTX for 3 weeks, followed by MP/MTX, cyclophosphamide/doxorubicin, and teniposide/cytarabine administered sequentially over 18 months. The final 12 months of treatment for both groups was MP and oral MTX; all patients received intrathecal MTX every 12 weeks. With a median follow-up of 5 years, complete remission durations have been significantly longer among children treated with HDMTX, compared with RTSC (P = .049) or historical institutional control regimens (P = .002). Approximately 67% of the patients receiving HDMTX and 56% of those receiving RTSC are expected to be in continuous complete remission at 4 years. Overall, isolated CNS relapse rates were similar (P = .17) in the two treatment groups, although by newer risk criteria cranial irradiation could be expected to provide better protection in patients with an unfavorable prognosis. These findings indicate that addition of intermittent HDMTX infusions to conventional chemotherapy is an effective method for extending complete remissions in children with ALL.     

Bone marrow transplantation from matched related donors for patients with Fanconi anemia using low-dose busulfan and cyclophosphamide as conditioning

Seventeen patients with Fanconi anemia (FA) underwent allogeneic bone marrow transplantation (BMT) from matched related donors (MRD) between January 1999 and June 2003. Median age at BMT was 11 years. Conditioning regimen consisted of low-dose cyclophosphamide (CY; 40 mg/kg) and busulfan (BU; 6 mg/kg) with the addition of lymphoglobulin (20 mg/kg) in two patients. Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A (CsA) and methotrexate (MTX; 5 mg/m(2) at day 1, 3, 6). All patients engrafted (for an absolute neutrophil count >0.5 x 10(9)/L) after a median time of 12 days (range 10-16 days). Fourteen patients (82%) had sustained grafts, whereas three others (18%) rejected grafts between day +39 and +80 after transplantation. Two of them are still alive after successful second PBSC transplantation and one died. Acute and chronic GVHD occurred in 23% and 13% of patients, respectively. With a median follow-up of 16 months (range 3-53 months), survival rate was 72% and Karnofsky score was at least 90%. The low-dose BU/CY regimen, in FA patients allografted from an HLA-matched related donor, allowed engraftment with relative low toxicity. Early graft failure (GF) remains a problem and may require modification of this regimen.     

低温对新生大鼠缺氧缺血性脑损伤的保护作用及其机制

目的　探讨全身低温对缺氧缺血性脑损伤的保护作用及其机理。方法　结扎 7日龄Wistar大鼠左侧颈总动脉后吸入 7 7%氧气 6 0min制成脑缺氧缺血 (HI)模型 ,随机分成低温组(30℃ ,n =18)和常温组 (36℃ ,n =18)给予维持恒定目标温度 10h。在HI后 2 4h ,每组 8只取脑进行匀浆用于半胱天冬酶 2 ,3(caspase 2 ,3)活性测定和Western蛋白印迹检查 ,其余每组 10只在HI后 72h处死 ,取脑进行石蜡包埋 ,冠状切片 10 μm用于活性caspase 3,凋亡诱导因子 (AIF) ,发夹寡核苷酸探针原位杂交 (HPP)检测凋亡及相关因子 ,微管相关蛋白 2 (MAP 2 )免疫组化染色用于计算脑梗塞体积和海马CA1神经元丢失 ,HE染色计算脑损伤积分。结果　常温组在HI后 2 4h损伤侧大脑半球caspase 2 ,3的活性 [(2 7 7± 14 7)、(94 9± 5 3 1) pmol/(min·mg蛋白 ) ]均明显高于正常对照组 [(7 6± 0 7)、(12 9± 0 5 ) pmol/(min·mg蛋白 ) ]和低温干预组 [(7 9± 3 4 )、(2 1 1± 18 7)pmol/(min·mg蛋白 ) ],P <0 0 1;而低温组与正常对照组相比无明显差异。Western蛋白印迹结果显示低温组caspase 3的激活受到明显抑制。免疫组化显示常温组活性caspase 3及AIF的阳性细胞数(中位数 14 8 5 ;2 2 /视野 )明显高于低温组 (中位数 4 8 5 ;9/视     

Feasibility and safety of peripheral blood stem cell collection in children with poor-prognosis solid tumors: a single center experience.

This study reports the data of 32 children with poor-prognosis solid tumors who had 78 PBSC harvests on Fenwall CS-3000plus after mobilization mainly by different treatment protocol chemotherapy regimens followed by G- or GM-CSF (92% of patients) or by G-/GM-CSF alone (8%). Timing of procedure was predicted by studying the blood count. When the white blood cell and platelet count reached a median of 8.1 (0.9-37.3) and 95 (16-338) x 10(9)/L, respectively, the median number of 2.7 (0.005-16.8) x 10(6) CD34+/kg with 1.5 (0.005-11.6) x 10(6) CD34+/kg for 1 blood volume processed was obtained per procedure. In the group of 13 patients with low body weight (median 14 [10-20] kg) 32 leukophereses were performed. The extracorporal line was primed with donor red blood cells in the patients with the weight below 15 kg. No difference was observed in CD34+ content in harvests whether GM-CSF was begun on day +1 or on day +3 after chemotherapy.     

Incidence, clinical markers and prognostic significance of immunologic subtypes of acute lymphoblastic leukemia (ALL) in children: experiences of the ALL-BFM 83 and 86 studies

In the therapy studies ALL-BFM 83 and 86, immunophenotyping of ALL by monoclonal antibodies was performed in a total of 1162 protocol patients (ALL-BFM 83 n = 578; ALL-BFM 86 n = 584). Both studies yielded similar results with respect to the incidence of immunological subtypes: CD10-negative pre-pre-B ALL (ALL-BFM 83: 3.6%; ALL-BFM 86: 5.3%), common ALL (80.1%; 77.9%), B-ALL (1.9%; 2.8%), pre-T/T-ALL (13.9%; 13.5%). Leukemic cells of 3 patients in the ALL-BFM 83 study lacked lymphoid and myeloid antigens (acute unclassifiable leukemia, 0.5%), and 3 patients in the ALL-BFM 86 study exhibited different blast populations with expression of either myeloid or lymphoid features (acute mixed-lineage leukemia, 0.5%). Coexpression of myeloid antigens (CD13 and/or CD33 and/or CDw65) on lymphoblasts (My-positive ALL) was identified in 35 of the 570 (6.1%) protocol patients prospectively analyzed in the ALL-BFM 86 study. The following associations were observed between the immunological subtype and the clinical risk factors: median age (years)-pre-pre-B 3.0, common 4.3, B- 7.9, pre-T/T-ALL 8.5 (pre-pre-B, common vs. pre-T/T-ALL p = 0.05); median leukocyte counts (x 10(9)/l)-pre-pre-B 80, common 9.1, B- 12.3, pre-T/T-ALL 68.1 (common, B- vs. pre-pre-B, pre-T/T-ALL p less than 0.05). The prognostic relevance of the immunophenotype was evaluated on the basis of the therapeutic results obtained in the ALL-BFM 83 study. A significant difference in the remission rate was only recognizable between patients with common ALL (99.1%) and those with pre-T/T-ALL (93.7%, p less than 0.001). After a median follow-up of 54 months, the probability of event-free survival is 71% for pre-pre-B ALL, 67% for common ALL, 56% for pre-T/T-ALL and 27% for B-ALL (common vs. B-, pre-T/T-ALL p less than 0.001), the prognosis in patients with pre-pre-B and common ALL being markedly influenced by the initial leukocyte counts and the age.     

Prognostic implications of t(10;11) translocations in childhood acute myelogenous leukemia: a report from the Children's Cancer Group

PURPOSE: This was a retrospective analysis of outcome based on cytogenetics for a Children's Cancer Group phase 3 trial of acute myelogenous leukemia (AML) (CCG-2891). PATIENTS AND METHODS: A retrospective analysis of outcome for newly diagnosed children with AML and myelodysplastic syndrome (MDS) was performed using data collected from CCG-2891. The authors identified 11 patients whose blasts carried t(10;11) reciprocal translocations or other complex rearrangements involving 10p and 11q among 470 eligible patients entered with acceptable, centrally reviewed cytogenetics. A bone marrow specimen was used for each case of cytogenetic analysis in which 20 banded (either G-banded or Q-banded) metaphases were completed on each subject. All 11 patients had characteristic monocytoid morphology (M4 or M5) and tended to be young (0.1-7.9 years; median 0.9 years). RESULTS: All 11 patients entered remission, but remissions tended to be short; 9 patients relapsed within 12 months (median 4 months). The relapse rate of 82% was significantly higher for this group of patients compared with 46% for the group at large. The relapse rate for this group of patients having t(10;11) reciprocal translocations or other complex rearrangements involving 10p and 11q was also significantly higher compared with subjects with other 11q23 chromosomal abnormalities. The CNS relapse rate of 55% was higher for this group of patients compared with 3% for all other patients in the study. The CNS relapse rate was higher for the subjects who had t(10;11) reciprocal translocations or other complex rearrangements involving 10p and 11q compared with subjects with all other chromosome 11 abnormalities. Three children survived, two in second remissions (4.7 and 6.3 years after relapse) and one in first remission (7.0 years after diagnosis). Survival and event-free survival for the patients with t(10;11) reciprocal translocations or other complex rearrangements involving 10p and 11q was 27 +/- 27% and 9 +/- 17% at 6 years, respectively, and was not statistically different from all other patients with cytogenetics. Similarly, the survival and event-free survival for the patients with t(10;11) translocations and other rearrangements of chromosomes 10 and 11 was 27 +/- 27% and 9 +/- 17% at 6 years, respectively, and was not statistically different from the 11q23 group of subjects.CONCLUSIONS: Further research is needed to determine the various changes that are occurring at the molecular level for patients with t(10;11) translocations and other rearrangements of chromosomes 10 and 11 to gain insight into the mechanisms causing this clinical phenotype associated with a poor prognosis.