A pilot study of prophylactic ciprofloxacin during delayed intensification in children with acute lymphoblastic leukemia

BACKGROUND: We hypothesized that prophylactic administration of an appropriate antibiotic following each delayed intensification (DI) in children with acute lymphoblastic leukemia (ALL) would reduce the episodes of fever and bacteremia associated with neutropenia, and hence reduce both the rate and duration of hospitalization. PROCEDURE: All patients in the study were treated according to a modified Medical Research Council United Kingdom ALL XI (MRC UKALL XI) protocol utilizing three DI courses. Between June and December 2000 patients received prophylactic ciprofloxacin following DI courses. The rates of hospitalization and bacteremias were compared to ALL patients who had received between one and three DI courses prior to June 2000. RESULTS: There were 69 patients who received a total of 194 DIs (controls 130; study group 64). The rate of hospitalization was 90% in the controls and 58% in the study group (P < 0.001). The median hospital stay was 10.1 days for controls and 6.0 for the study group (P < 0.001). Intensive care unit admissions were reduced from 12 to 1.5% (P = 0.02). The overall rate of proven bacteremia was reduced from 22 to 9% (P = 0.028). There were no Gram-negative bacteremias in the study group compared to 10 (7.7%) in the controls (P < 0.001). CONCLUSIONS: Compared to historical controls, patients in this study receiving prophylactic ciprofloxacin had a reduced rate and duration of hospitalization and incidence of Gram-negative bacteremia.     

Severe infections in childhood leukemia. A follow-up study of 100 consecutive ALL patients

Severe infections during the course of childhood ALL were surveyed as a whole in 100 consecutive patients, followed up for 2-8.5 years from the ALL diagnosis. The most important findings were a total absence of disseminated candidiasis, a relative infrequency of gram-negative septicemia (8 episodes), and a predominance of gram-positive cocci (29 episodes) in the 48 verified septicemias. S. aureus was responsible for 50% of culture-positive septicemias. The gram-positive predominance depended probably on local factors, and reservation in using broad-spectrum antibiotics might have played a part. There were 9 cases of disseminated Varicella-zoster, cured successfully with antiviral agents. Pneumocystis carinii pneumonitis numbered 8 episodes, concentrated to the early remission period. One case of miliary tuberculosis was found. Risk factors regarding age of patient and phase or intensity of cytotoxic therapy are evaluated.     

儿童白血病中34种ph样ALL基因筛选的临床研究

目的对白血病儿童进行34种ph样ALL基因筛选,明确其在预后评估中的临床意义。方法 2016年2月-2018年10月上海市儿童医院119例初发ALL患儿,男69例,女50例,年龄6个月～17岁,应用实时荧光探针PCR法进行Ph样ALL相关34种基因的筛选,筛选阳性者再进行监测。统计学方法应用SPSS 16. 0进行χ~2检验和生存分析。结果 119例初发ALL患儿,ALL-B109例,ALL-T 10例,ph样ALL基因筛选的阳性率为18. 5%(22/119)。阳性的ph样ALL基因包括:IKZF3-8(IK6) 8例次,CRLF2高表达16例次,EBF1-PDGFRB 1例次。其中3例为2种基因同时存在:IKZF3-8和CRLF2高表达共阳性2例,IKZF3-8和EBF1-PDGFRB共阳性1例。上述119例ALL分为ph样ALL基因阳性组(22例)和ph样ALL基因阴性组(97例)。第19天和第46天的流式MRD监测结果两组差异无显著性。ph样ALL基因阳性组总体生存率低于阴性组(P=0. 037),而无事件生存率无差异(P=1. 0)。结论 ph样ALL基因阳性患儿总体生存率降低,可用于儿童白血病的预后评估。     

A randomized study of intermittent chemotherapy with or without BCG inoculation in maintenance therapy of childhood ALL

One hundred ninety-six children with acute lymphocytic leukemia were entered into a randomized study of maintenance chemotherapy with either intermittent chemotherapy and immunotherapy with bacillus Calmette-Guerin (BCG) or only intermittent chemotherapy. On admission to the study, patients were stratified into three prognostic categories on the basis of clinical and laboratory features at presentation. Patients considered to have a favorable prognosis (PF) were induced with vincristine and prednisone; those with an unfavorable prognosis (PU) received combination chemotherapy consisting of either Ara-C, cyclophosphamide and asparaginase, or vincristine, prednisolone, and daunomycin followed by Ara-C and asparaginase; those with an average prognosis (PA) received vincristine and prednisolone followed by a single course of Ara-C and asparaginase. All patients received central nervous system prophylaxis with 2,400 rad cranial irradiation and four injections of intrathecal methotrexate. One hundred seventy-seven patients (90%) achieved complete remission, and 165 were randomized. Those randomized to Group A (83) received maintenance chemotherapy with six-week courses of 6-mercaptopurine, weekly oral methotrexate, and monthly vincristine. Each six-week course was followed by a two-week interval of no chemotherapy, and treatment was con tinued for 36 months. Patients randomized to Group B (82) received the same maintenance chemotherapy, but during the two-week interval without chemotherapy, they were given BCG inoculation. With a median follow-up of 110 weeks, no significant difference in duration of remission, survival, or CNS relapse was found between Groups A and B in the total patient population or within each prognostic category. In patients classified as PU, a significantly lower proportion (P < 0.02) remained in complete remission. Within this group, patients with a white cell count > 100 × 10⁹/L had a significantly shorter duration of remission (P < 0.05). Patients classified as PF showed a This research was done by the Australasian Cancer Society Childhood Leukemia Group.     

Vindesine in relapsed childhood ALL. A pilot study by the United Kingdom Children's Cancer Study Group

Twenty-three children with first on-treatment marrow relapse of lymphoblastic leukaemia (ALL) were randomly assigned to treatment with vincristine (16 patients) or vindesine (7 patients) in an otherwise identical regimen including daunorubicin, prednisolone, asparaginase, VM26 and cytosine. There was no suggestion of any difference between the two groups in terms of frequency of secbnd remission achievement or duration, nor was there in terms of toxicity. Despite small numbers, these findings suggest that vindesine does not offer any obvious therapeutic advantage over vincristine in relapsed ALL, but is well tolerated.     

Efficacy of prophylactic additional cranial irradiation and intrathecal chemotherapy for the prevention of CNS relapse after allogeneic hematopoietic SCT for childhood ALL

We evaluated the efficacy of CRT and IT chemotherapy, in addition to conditioning including TBI, for the prevention of CNS relapse, in allogeneic HSCT for childhood ALL. From January 1999 to December 2009, a total of 48 patients, without previous or presenting CNS involvement, underwent HSCT for ALL. All patients received myeloablative conditioning including TBI of 12 or 13.2 Gy and IT chemotherapy twice between days ?10 and ?2 prior to HSCT. Twenty‐five patients received CRT prior to TBI (CRT+), and 23 patients did not (CRT?). CRT+ and CRT? patients had a seven‐yr EFS rate of 40.0 ± 9.8% and 41.7 ± 10.6%, respectively (p = 0.8252). The seven‐yr relapse rates for CRT+ and CRT? patients were 45.0 ± 11.2% and 38.4 ± 11.6%, respectively (p = 0.7460). CNS relapses were evident in 1 (4.0%) CRT+ patient and 1 (4.4%) CRT? patient (p = 1.000). There were no significant differences in EFS and the probability of CNS relapse between CRT+ and CRT? patients. These results demonstrate that CRT and IT chemotherapy, in addition to conditioning chemotherapy, may not be necessary in childhood ALL patients without previous or presenting CNS involvement.     

CNS late-effects after ALL therapy in childhood. Part III: neuropsychological performance in long-term survivors of childhood ALL: impairments of concentration, attention, and memory

PURPOSE: To date, the event free survival (EFS) after treatment of childhood acute lymphoblastic leukemia (ALL) attains 80%. The survivor group is growing steadily. Therefore, the primary purpose of our study is to define the neuropsychological function and to describe which central nervous system (CNS) functions are impaired following the German ALL-BFM and COALL protocols for CNS-negative patients.Patients and METHODS: In a cross-sectional multicenter study 121 subjects, long-term survivors of childhood ALL in first continuous complete remission were investigated. Seven years ago, the subjects were treated as standard or medium risk patients according to ALL-BFM 81, ALL-BFM 83, or COALL 82 protocols, receiving comparable treatments. According to different CNS-prophylaxes, two subgroups were compared in the study: the non-cranially irradiated MTX-group (methotrexate-group) (n = 38) and the cranially irradiated RT-group (radiotherapy-group) (with MTX i.th.) (n = 83). Intellectual and cognitive abilities of these groups were evaluated using standardized psychometric techniques. The Kaufman factors Verbal Comprehension, Perceptual Organisation and Freedom from Distractibility were calculated. Demographical and clinical data collected at the time of the diagnosis were compared between both groups. The different prognoses for patients within both groups were taken into account using a defined risk factor. Analysis of variance was conducted to relate intellectual performance to age, gender, and CNS-treatment. RESULTS: The RT-group exhibited a lower Full Scale IQ than the MTX-group (101.2 +/- 15.9 vs. 109.9 +/- 14.9, P = 0.031). Particularly for the Kaufman factor Freedom from Distractibility the RT-group showed the lower scores (96.9 +/- 14.1 vs. 105.5 +/- 12.6, P = 0.037). Significant interactions between gender and CNS prophylactic treatment were observed for Full Scale IQ (P = 0.008), Verbal IQ (P = 0.012), Performance IQ (P = 0.024), Verbal Comprehension (P = 0.004), and Perceptual Organisation (P = 0.032). CONCLUSIONS: Cranial irradiation in combination with MTX therapy was associated with deficits in attention, concentration, and the ability of sequencing and processing, measured by the Kaufman factor Freedom from Distractibility. Our results support the strategy of avoiding prophylactic CNS irradiation in low risk patients.     

A study of brucellosis in childhood

Two hundred children with brucellosis are described. The clinical characteristics on presentation included prolonged fever, arthralgia, weight loss, and malaise in the majority of the patients. Biochemical characteristics included a relative lymphocytosis in 92.9 percent of the patients and elevated liver enzymes in 83.5 percent. The Brucella agglutination titer was 1:320 or more in all the cases studied, but repeated blood cultures yielded growth of Brucella organisms in only 42 percent of the patients. Brucellosis is an important cause of fever in children living in areas where Brucella-infected animals are raised. Consumption of raw milk or dairy products made from raw milk are the main sources of infection. Education of the public and governmental control are necessary to eradicate the disease.     

The Munich study on the treatment of acute lymphoblastic leukemia in childhood (ALL 77-02)

149 children with acute lymphocytic leukemia (ALL) were admitted to a prospective therapeutic regime. Remission induction was achieved by vincristine, daunorubicine, L-asparaginase and prednisone. During consolidation the patients received three intermediate dose methotrexate (MTX) infusions over 24 hours combined with intrathecal MTX, followed by L-asparaginase. High-risk patients were treated in addition with high dose cyclophosphamide and ARA-C over 3 weeks. Standard risk patients received cranial irradiation with 18 Gy, high-risk patients with 24 Gy. Maintenance therapy was performed with 6-mercaptopurine and MTX orally. Immunologic phaenotyping revealed: c-ALL 73%, pre-T or T-ALL 15%, c/T-ALL 4% and undifferentiated leukemia (AUL) 8%. Only 1 patient was nonresponder, 7 patients died during induction therapy, 5 patients during continuous complete remission (CCR). 18 relapses occurred, 12 of which were systemic, 8 CNS and 2 testicular relapses. In the total group the 54 months probability of CCR is 0,68 +/- 0,05 (life-table-analysis), for the reduced group 0,75 +/- 0,05. In the reduced group the probability of CCR at 54 months for standard risk patients is 0,86 +/- 0,06; for high-risk patients 0,60 +/- 0,09; for patients with c-ALL 0,73 +/- 0,08; for patients with c/T-ALL 1,0 +/- 0,0; for patients with pre-T or T-ALL 0,58 +/- 0,2 and for patients with AUL 0,45 +/- 0,25. For the reduced group the CCR probability at 54 months in relation to the leukocytes (WBC) at diagnosis is in patients with WBC less than 25 X 10(3)/mm3: 0,80 +/- 0,06; for patients with WBC greater than 25 X 10(3)/mm3: 0,63 +/- 0,11.     

Immunologic profile and outcome of childhood acute lymphoblastic leukemia (ALL) in Morocco

Immunophenotyping in leukemia offers a precise delineation of the hematopoietic lineage and differentiation stage of the malignant cell. In this study, we used flow cytometry to determine the frequency of the immunologic types of acute lymphoblastic leukemia (ALL) in Moroccan children. We analyzed 100 samples from ALL patients within an age ranging from 6 months to 16 years presented over a 4-year period (1996 to 2000). Immunophenotyping allowed classification into 2 major categories: T-ALL (37%) and B-ALL (63%), with a higher percentage of males (69%). Comparison of the clinical characteristics showed that the frequency of splenomegaly was similar in B-ALL and T-ALL patients (53% and 47%, respectively). Hepatomegaly and mediastinal masses were more often associated with T-ALL (62% and 71%, respectively). Splenomegaly, hepatomegaly, and mediastinal masses were more frequent in immature than mature B-ALL, whereas the reverse was observed for T-ALL. Complete remission was obtained in 88% and 84% of B-ALL and T-ALL, respectively and relapse after 1 year occurred in 30% and 37% of cases, respectively. CD10 expressing B-ALL showed a slightly higher complete remission rate, whereas the reverse was observed for CD10 expressing T-ALL. The overall 5-year survival rate of ALL was 38%, whereas patients with B-ALL showed better survival than children with T-ALL.     

儿童急性淋巴细胞白血病微小残留病研究及应用进展

急性淋巴细胞白血病(ALL)是儿科最常见的恶性肿瘤性疾病,随着化疗方案的不断改进与完善,其缓解率已达90%以上,长期无病存活率已达80%左右,但仍有20%左右的患儿复发而最终死亡.且化疗药物在治疗肿瘤的同时也会给患儿的正常组织和生长发育带来损害,因此如何防止复发、如何避免不必要的过度化疗一直是儿科血液肿瘤研究者期待解决的问题.     

A clinico-bacteriological study of meningitis in infancy and childhood

Summary Meningitis constituted 1.7% of the total paediatric admissions. Of these cases, 0.97% were of tuberculous meningitis and 07.% cases were suffering from pyogenic meningitis. The maximum number of patients was encountered under 3 years of age with a significant male preponderance. Cranial nerve palsies and ocular changes were observed more frequently in tubercular meningitis. The flotation hydrocarbon test was helpful in demonstrating acid fast bacilli in 24.1% cases whereas direct smear was negative in all cases. Bacteriological examination revealed infection with pneumococci, meningococci, staphylococci andH. influenzae in that order of frequency. From the Department of Paediatrics, Gandhi Medical College, Bhopal.     

Pulmonary function following allogeneic stem cell transplantation in childhood: A retrospective cohort study of 51 patients

HSCT is associated with a high risk of late morbidity. The aim of this study was to evaluate the frequency, time frame, risk factors, and possible etiology of pulmonary dysfunction following allogeneic HSCT in childhood. We evaluated the pulmonary function of 51 HSCT patients (>6 yr), by including FVC and FEV1 values prior to (baseline) and annually up to five yr after HSCT. A Cox proportional hazards model was used to analyze the risk factors for a pulmonary event. Over half (59%) of the patients developed pulmonary dysfunction, mainly consisting of restrictive abnormalities. Acute GvHD (HR 4.31, 95% CI 1.47–12.63), chronic GvHD (HR 10.20, 95% CI 2.42–43.03), and an abnormal baseline pulmonary function (HR 4.82, 95% CI 1.02–22.84) were associated with post‐transplant dysfunction. FEV1 (p < 0.001) and FVC (p < 0.001) declined significantly by 12 months after HSCT and both remained below the pre‐HSCT level at up to four yr post‐transplantation. HSCT in childhood is associated with early and persistent restrictive impairment of pulmonary function. Patients with extensive chronic GvHD are particularly vulnerable to severe pulmonary dysfunction. Scheduled pulmonary function testing is warranted as part of the follow‐up of survivors of HSCT in childhood.     

DNA index and %S-phase cells determined in acute lymphoblastic leukemia of children: A report from studies ALL V,ALL VI,and ALL VII (1979–1991) of the dutch childhood leukemia study group and the Netherlands workgroup on cancer genetics and cytogenetics

DNA per cell content was routinely recorded by single-parameter flow cytometry in leukemic blasts from 473 children with acute lymphoblastic leukemia (ALL), enrolled in national studies ALL V, VI, and VII (1979–1991) of the Dutch Childhood Leukemia Study Group. The parameters bonemarrow %S-value and DNA Index were compared with clinical features, with chromosome number based on cytogenetic analyses and with treatment results in study ALL VI. %S-values, ranging between 1 and 36%, were unrelated to initial white blood cell count, immunophenotype, and DNA index but were lowest in blasts with L1 morphology. In study ALL VI (non-high risk), the survival of patients with ≦6% S-phase cells was superior to that of patients with %S-values of >6 (P = 0.030). Hyperdiploidy, defined by a DNA index ≧1.16, was compared to the cytogenetic hyperdiploid classification of n > 50. Initially there were 25 discrepancies in 189 samples jointly analysed by flow cytometry and cytogenetics. After review only five discrepancies remained unresolved. Hyperdiploidy, independent of the method used, was found to be unrelated to blast morphology and %S-phase cells but closely associated with c-ALL and was absent in T-ALL. In study ALL VI, event-free survival at 8 years of hyperdiploid patients was 90.6% but was not significantly different from non-hyperdiploid patients (EFS = 82.1%; P = 0.08). Routine DNA flow cytometry appeared a valuable adjunct to cytogenetic analyses and allowed the identification of a large subset of non-high-risk ALL patients in study ALL VI with a DNA index ≥1.16 or %S-value of ≦6.0 with highest survival probability. © 1995 Wiley-Liss, Inc.