Mucormycosis diagnosed during induction chemotherapy in five pediatric patients with acute lymphoblastic leukemia

Mucormycosis in pediatric oncology patients is a rare invasive fungal infection associated with significant morbidity and mortality. We describe five patients diagnosed with mucormycosis during induction chemotherapy for acute lymphoblastic leukemia at our institution. All of the patients in our series survived, some in spite of having disseminated disease. Most of the patients’ chemotherapy was modified with the aim of controlling their leukemia while minimizing immunosuppression until their fungal infection was under control. Although mucormycosis is frequently fatal, rapid diagnosis and a multidisciplinary approach can lead to excellent outcomes, even in patients undergoing intensive chemotherapy.     

Parvovirus B19 infection in a child with acute lymphoblastic leukemia during induction therapy

Immunocompromised children, including those undergoing chemotherapy treatment of malignant disease, are at particular risk for infection with parvovirus B19. However, these patients' attenuated immune responses may obscure the serologic and clinical manifestations of the infection. The authors describe a patient undergoing induction therapy for acute lymphoblastic leukemia whose parvovirus B19 infection was identified by the incidental detection of giant pronormoblasts and absence of normal mature erythroid precursors, characteristic of parvovirus infection, on a routine bone marrow examination. Intravenous immunoglobulin was administered and the patient's aplastic anemia resolved completely within 3 weeks. This highlights the importance of alertness to the possibility of parvovirus infection in children with cancer.     

Candida albicans arthritis during induction treatment of acute lymphoblastic leukemia]

Candida arthritis is a rare event which is a result of direct intraarticular inoculation, or--in compromised host--of hematogenous spread. We report on the case of an 18-month-old boy who experienced such an infection during induction treatment for acute lymphoblastic leukemia with aplastic onset. He was healed by daily systemic amphotericin B administered over a period of 3 wks associated with intravenous flucytosine during the first 2 wks; the treatment was continued with oral administration of ketoconazole for 5 wks. Treatment control was performed by drug monitoring in plasma and synovial fluid, as well as by determination of Candida antigenemia and antibody levels. We consider that the required doses of amphotericin B should be based upon plasma concentrations greater than 0.5 or 1 mg/l to be maintained during 2-3 wks. Providing that there is no resistance, the association with flucytosine may be useful.     

Successful treatment of pediatric plasmacytoid dendritic cell tumors with a contemporary regimen for acute lymphoblastic leukemia

Dendritic cell leukemia (DCL) or hematodermic tumor is an uncommon subtype of acute leukemia. In contrast to adult cases, children tend to have a less aggressive course. The diagnosis of DCL should be considered when its characteristic morphologic features are present and leukemic cells co‐express CD4 and CD56. Cases of DCL among pediatric patients have been reported to respond to therapeutic regimens for acute lymphoblastic leukemia, but details regarding the specifics of therapy are lacking. Pediatr Blood Cancer 2013; 60: E38–E41. © 2013 Wiley Periodicals, Inc.     

Concurrent acute lymphoblastic leukemia and juvenile pilocytic astrocytoma in a pediatric patient

The concurrence of acute lymphoblastic leukemia (ALL) and an asymptomatic juvenile pilocytic astrocytoma is described. A 6-year-old boy without clinical evidence of neurofibromatosis had a juvenile pilocytic astrocytoma diagnosed on radiologic examination and before treatment of acute pre-B cell lymphoblastic leukemia. The patient has had a partial resection of the astrocytoma and is 9 months into treatment of his ALL, which is in complete remission. p53 gene mutation was not identified in this patient. The concurrent diagnosis before treatment of ALL and juvenile pilocytic astrocytoma, the latter normally an indolent tumor, suggests that some cases of astrocytoma previously ascribed to radiotherapy or other treatment may in fact be caused by other factors.     

Successful treatment of acute lymphoblastic leukemia in a child with cystic fibrosis

A 3 1/2 year old girl with cystic fibrosis who underwent successful treatment for acute lymphoblastic leukemia remains in complete remission 36 months after diagnosis. We also report high clearance rates of three antineoplastic agents in this patient. Drug doses were adjusted to achieve optimal systemic exposure. © 1994 Wiley-Liss, Inc.     

Successful treatment of aspergillus brain abscess in a child with acute lymphoblastic leukemia

Cerebral aspergillosis carries a high mortality in immunocompromised patients. However, favorable outcome can be achieved by the prolonged use of antifungal agents and the maintenance of adequate drug levels. The authors report a 2-year-old girl who developed an aspergillus brain abscess during treatment for acute lymphoblastic leukemia. Predisposing factors for thefungal infection and details of the antifungal therapy are described. Prolonged treatment with AmBisome and 5-flucytosine successfully eradicated the lesion, but the girl's antileukemic therapy was compromised due to the infection. She developed a central nervous system and bone marrow relapse 9 and 15 months, respectively, after the initial presentation. The report emphasizes the need for further consideration of effective, long-term anti fungal prophylaxis and a careful balance between aggressive treatment for severe infection and antileukemic therapy.     

Simultaneous occurrence of MLL and RARA rearrangements in a pediatric acute lymphoblastic leukemia patient

We report a case of concurrent translocations of MLL gene, associated with a highly distinct leukemia subtype and RARA gene, which is pathogenomic in acute promyelocytic leukemia. Conventional cytogenetic revealed a novel complex rearrangement between chromosomes 5, 11, and 17 resulting in a three‐way chromosome translocation t(5;11;17)(q31;q23;q21). Fluorescence in situ hybridization analysis demonstrated that the 11q23 breakpoint involved the MLL, and the 17q21 breakpoint involved the RARA gene. Concurrent translocations of two specific oncogenes MLL and RARA with a new partner breakpoint on 5q31 have not been previously described. Pediatr Blood Cancer 2009;52:671–674. © 2009 Wiley‐Liss, Inc.     

Urolithiasis in an acute lymphoblastic leukemia child during induction chemotherapy

An 11-year-old acute lymphoblastic leukemia patient suddenly developed severe abdominal flank pain and hematuria caused by renal stone during induction chemotherapy. The patient was treated with forced hydration, and the pain was relieved after the renal stone passed through. The renal stone was composed of calcium phosphate. The patient is currently in continuous complete remission, has had no recurrence of the urolithiasis, and is on consolidation chemotherapy. Although urolithiasis is extremely rare in childhood acute lymphoblastic leukemia, it should be considered in patients who complain of abdominal flank pain or back pain during chemotherapy.     

Chemotherapy related fatal neurotoxicity during induction in acute lymphoblastic leukemia

Neurotoxicity is a common complication during cancer chemotherapy. It is estimated that 3–10% of children with acute lymphoblastic leukemia (ALL) experience acute, transient neurotoxicity during induction chemotherapy. Fatal acute neurotoxicity is rarely encountered. Neurological evaluation of children with ALL at diagnosis and during treatment is of value in order to diagnose neurological complications early so that appropriate intervention can be adopted. This communication describes the profile of two children with unexpected, acute fatal neurologic toxicity during induction chemotherapy for ALL.     

Parvovirus B19 infection as a cause of anemia in pediatric acute lymphoblastic leukemia patients during maintenance chemotherapy

PURPOSE: Persistent parvovirus B19 tends to occur in immunocom-promised patients and manifests as pure red cell aplasia and chronic anemia. This study aimed to detect the contribution of parvovirus B19 infection to anemia in children with acute lymphoblastic leukemia (ALL) receiving chemotherapy. PATIENTS AND METHODS: Two groups of ALL patients were studied during maintenance chemotherapy: 50 patients with persistent anemia (ie, extending for >2 weeks) and 34 patients without anemia (controls). Serum parvovirus B19 IgG and IgM were investigated by an enzyme-linked immunosorbent assay, and the virus DNA was sought in bone marrow cells by a nested polymerase chain reaction assay. RESULTS: Parvovirus B19 DNA was detected in 11 of the 50 (22%) ALL children with anemia, 4 of whom were also IgM positive. In addition, IgM positivity was observed in nine (18%) other children who were negative for parvovirus B19 DNA. The children without anemia were found to be significantly different than those with anemia in terms of parvovirus B19 DNA positivity and DNA + IgM positivity (P = 0.03 and 0.01, respectively). IgG was found to be positive in a total of 19 (38%) cases, with B19 DNA present in 6 of them. CONCLUSIONS: These findings indicate the high frequency of parvovirus B19 in anemia in children with ALL and the importance of testing for its DNA in the bone marrow cells together with IgG and IgM antibodies in the serum of immunocompromised patients. It is important to consider parvovirus B19 infections as a cause of anemia and suppressed erythropoiesis in children with ALL who are receiving ongoing treatment.     

儿童急性淋巴细胞白血病应用门冬酰胺酶治疗的临床研究

目的回顾性总结和分析应用左旋门冬酰胺酶(L-Asp)治疗儿童急性淋巴细胞白血病(ALL)的经验、不良反应及其应对措施,以期对未来用药提供借鉴。方法 102例ALL患儿入组。分析超敏反应对疗效的影响,总结凝血功能异常及暂时性高血糖(TH)的应对措施,对L-Asp相关胰腺炎(AAP)病例作简要总结。结果(1)34例(33.3%)出现超敏反应,多数程度较轻且发生于诱导期以后的治疗过程中。(2)PT延长16例(20.3%),APTT延长17例(21.5%),FIB不同程度降低,50例(63.3%)低于1g/L,4例(5.I%)低于0.5g/L。(3)70例(68.6%)出现不同程度的血糖升高,11例(10.8%)诊断TH,其中4例(36.4%)有高血糖家族史。(4)4例(3.9%)发生AAP,1例再次应用L-Asp后未出现AAP。结论(1)超敏反应组和无超敏反应组的预计5年OS和EFS差异无显著性。(2)L-Asp治疗过程中出现的凝血功能改变原则上在无严重合并症时可不行预防性凝血因子的替代治疗。(3)高年龄组(≥6岁)及有糖尿病家族史者发生TH的可能性更大。(4)AAP发生后48 h内症状缓解、淀粉酶和脂肪酶低于正常值上限3倍以及影像学未提示假性囊肿或坏死者可尝试再次应用L-Asp化疗。     

Development of cold agglutinin autoimmune hemolytic anemia during treatment for pediatric acute lymphoblastic leukemia

Autoimmune hemolytic anemia (AIHA) is a potentially fatal complication of many lymphoid malignancies. Those most often associated with AIHA include chronic lymphocytic leukemia, B-cell lymphomas, and Burkitt-type acute lymphoblastic leukemia (ALL) and are clonal populations of mature B cells. There have been no reports of patients with B-cell precursor ALL who developed AIHA while undergoing chemotherapy, but AIHA has been reported in a few patients with ALL after hematopoietic stem cell transplant. The authors describe a child with B-cell precursor ALL who developed cold agglutinin AIHA during maintenance treatment while in remission after infection with influenza B.     

On the origin of EEG-slowing and encephalopathy during induction treatment of acute lymphoblastic leukemia

BACKGROUND: Neurological complications and EEG slowing frequently occur in children undergoing induction treatment for acute lymphoblastic leukemia (ALL). Disease-related factors and treatment-related toxicity are believed to play causative roles. We wanted to elucidate the etiology further by serial EEG examinations and parallel CSF amino acid analyses. PROCEDURE: Twenty-nine children participated in the study. EEG examinations with quantitative computerized analysis were scheduled on day 1, 10, 29, and 59 of protocol I of BFM-ALL 90 and 95 Study Protocols. CSF analysis for amino acids was carried out on day 1, 15, 29, 45, and 59. RESULTS: A total of 21 of 25 available EEGs showed slight-to-moderate slowing already at diagnosis. The abundance of slow waves was significantly correlated to the white blood count and the CSF glutamine concentration. The EEGs significantly worsened during the first 10 days of treatment with prednisone, VCR, daunorubicin, and intrathecal methotrexate. The following treatment including asparaginase (ASP) gave rise to depletion of CSF from asparagine and a rise of aspartate; glutamine, and glutamate did not follow this pattern. The EEGs remained abnormal, but did not worsen further; the CSF amino acid changes were not related to the EEG. During the subsequent consolidation treatment, the EEGs normalized despite administration of cyclophosphamide, cytara bine, intrathecal methotrexate, and mercaptopurin. CONCLUSIONS: The greater part of EEG changes observed in the early treatment of ALL is due to disease-related factors. Treatment with prednisone, vincristine, and to a much lesser degree asparaginase aggravates the pre-existing encephalopathy. Depletion of CSF from asparagine does not give rise to additional changes. In the second month, the EEG normalizes despite ongoing treatment with different cytotoxic drugs.