Erdheim Chester diseaseâAn unusual presentation of a rare histiocytic disease in a 3-year old boy

Erdheim Chester disease (ECD) is a rare, multisystem non-Langerhans histiocytosis seen in adults characterized by a clinical triad of bone pains, bilateral painless exophthalmos and diabetes insipidus. Only 10 pediatric ECD cases are reported. We report here the youngest child in the literature, diagnosed at three years of age. He presented with osteolytic lesions in the skull, diabetes insipidus and bilateral proptosis. He was initially misdiagnosed and treated as Langerhan cell histiocytosis(LCH). In ECD, the typical radiological findings are symmetrical osteosclerosis of long bones. Osteolytic lesions are rare and if present are usually seen in the limbs. This is the first pediatric case with osteolytic lesions solely in the skull. A repeat biopsy confirmed ECD with the presence of foamy histiocytes in fibrous background positive for CD68 andCD163 and negative for CD1a and S100, typical histopathological features of ECD. The BRAFgene mutation was also detected. The patient responded well to interferon alpha therapy, which is now considered the first line treatment in ECD

Megakaryocytic blast crisis at presentation in a pediatric patient with chronic myeloid leukemia

Patients with chronic myeloid leukemia (CML) infrequently present in blast crisis (BC). While most BC are of myeloid origin, megakaryocytic BC is rare, especially at the time of CML diagnosis. We describe the first pediatric patient presenting with megakaryocytic leukemia and having BCR-ABL1 translocation as the single chromosomal abnormality. Clinical features were more suggestive of CML in megakaryocytic blast crisis than Philadelphia chromosome positive de novo AML. The patient was treated with AML-directed chemotherapy and imatinib mesylate followed by umbilical cord blood stem cell transplantation. The patient was in complete molecular response 16 months after stem cell transplantation

Risk-adapted stratification for optimally intensive treatment assignment of pediatric patients with non-Hodgkin lymphoma is an effective strategy in developing countries

Background: Pediatric patients with non-Hodgkin lymphoma (NHL) in developing countries (DCs) present with greater tumor load even at lower stages and with comorbidities that impact therapy delivery. This causes toxic mortality with standard intensive protocols or recurrences with gentler treatment.Objectives: We developed and evaluated a risk stratification schema that guides intensity of therapy.Design/methods: Sixty-nine patients were prospectively assigned to five risk groups (A-E; n = 6, 15, 16, 15, and 17) following staging and treated with protocols of risk-stratified intensity. Risk stratification utilized St. Jude stage, disease bulk, and sites involved.Results: Between 2006 and 2011, 69 patients with B-cell NHL were enrolled. Among these, 72.5% were boys with mean age of 6.9 years (±3.33 [SD]; range 2.4-14.2 years). Eighty-seven percent had Burkitt lymphoma, 82.6% had advanced stage (25 [36.2%] stage III; 32 [46.4%] stage IV), and 24.6% were central nervous system positive. Mean lactate dehydrogenase increased progressively across the risk strata. Among these, 0/6, 1/15, 3/16, 2/15, and 7/17 patients relapsed/progressed within each risk stratum. Fifteen patients died; three from treatment-related toxicity. At a median follow-up of 6.2 years, the overall and event-free survival (EFS) for all patients was 78.1 and 75.4%, respectively; EFS was related to risk assignment. The frequency of documented infectious and noninfectious toxicities increased with higher risk group assignment causing prolongation of admissions and potential treatment delays.Conclusions: Reduction in treatment intensity for an identified subset of patients with NHL is feasible, while high-intensity therapy is required for high-risk groups. This risk stratification system may be a first step toward improving the outcomes in some DCs

Clinical characteristics and treatment outcome of pediatric patients with chronic myeloid leukemia

As chronic myeloid leukemia is rare in children, most data on imatinib mesylate therapy is derived from adult studies. We retrospectively evaluated pediatric (<14 years) patients with Ph+ chronic myeloid leukemia treated with imatinib mesylate, from January 2003 through June 2008. Of the 12 chronic myeloid leukemia patients (2% of all leukemias) 11 were in chronic phase while one had myeloid blast crisis. Six subsequently underwent stem cell transplantation. Five patients had grade 3–4 arthralgia requiring therapy alteration. None achieved complete molecular remission (MR) with imatinib mesylate alone. In contrast 3/6 patients post stem cell transplantation have undetectable BCR-ABL. Three patients relapsed to chronic phase (1 imatinib mesylate; 2 stem cell transplantation). Relapse free survival is 65.6% at four years and all are alive. Imatinib mesylate is effective therapy for children with chronic myeloid leukemia. However, cure probably requires stem cell transplantation. Acute toxicity of imatinib mesylate is tolerable, but long-term effects on growing children are unknown. Pediatric patients with chronic myeloid leukemia should undergo stem cell transplantation when appropriate related donors are available

Clinical characteristics and outcome of children with biphenotypic acute leukemia

This study from Saudi Arabia found that 4% of 633 cases of pediatric acute leukemia were biphenotypic. The authors describe the clinical features of these patients and their response to treatment including stem cell transplantation

113 Invasive fungal infections among pediatric patients with hematologic malignancies at KFSH&RC/KFCCC&R

Objectives: To define the magnitude of the problem, study factors associated with increased risk of invasive fungal, infections (IFI) and outcome.Methods: From June 1998 to March 2003, all, radiological, studies of patients with hematologic/ oncologic disorders were evaluated for inclusion. AII, cases of invasive fungal, infection were reviewed. The criteria for inclusion were obvious lesion suggestive of fungal, infection shown on radiological, studies, and fungal, infections were classified as proven , probable\u27, possible or insufficient evidence according to a prior definitions.Results: A total, of 1615 patient charts were reviewed. The underlying diagnoses include ALL 410, SCT 293, AML 133, non-malignant hematology 288, NHL/solid tumors 491. 152 (9%) had evidence of fungal, infection (55 [36%] \u27definite = proven/probable\u27, 97 [64%] \u27possible\u27). Biopsy was performed in 94 cases and the findings included budding yeast in 10 patients, septated hyphae in 19, and hyphae with no specifications in 12 patients. Delays in performing diagnostic procedures possibly resulted in the lower incidence of \u27definite\u27 IFI (36% vs 64% \u27possible ). The overall, incidence of fungal, infection was 9%, being highest for AML (39%), followed by ALL (17%). The majority of IFI developed during or immediately after induction (42% of IFI in AML and 53% of IFI in ALL), which can be a target for intervention. The infections included disseminated fungal, infection (36%), CDC (11%), pulmonary fungal, infection (43%) and aspergillosis (9.5%) including pulmonary, Para nasal, sinuses, skin and disseminated. IFI was radiologically diagnosed during neutropenia in 123 patients (81%). Ten patients died due to fungal, infection (7%), 75 (49%) were cured, 26 (17%) were alive with fungal, infection, and 39 patients (26%) died due to primary disease seemingly unrelated to fungal, infection. Mortality due to IFI in this study is less than what is reported in the literature and could be a result of our practice of early intervention. The average LOS for IFI was 56 days compared with the usual. 12 days, which can add to the increased cost.Conclusions: Invasive fungal, infection is becoming a serious problem. Furthermore, acute invasive fungal, infection is associated with a much higher mortality. Early diagnosis with prompt antifungal, therapy, or even with surgical, intervention, might be warranted to save patients\u27 lives

Dexamethasone-associated toxicity during induction chemotherapy for childhood acute lymphoblastic leukemia is augmented by concurrent use of daunomycin

Background: The goals of the current study were to examine the incidence and severity of toxicity resulting from dexamethasone and prednisone during induction therapy for children with precursor B-cell acute lymphoblastic leukemia (ALL) and to determine whether the addition of daunomycin affected toxicity.Methods: Medical records of patients with precursor B-cell ALL from January 1996 through June 2000 were reviewed retrospectively for toxicity during the 4-week induction phase and the 2 weeks after the induction phase.Results: One hundred seventy-six patients age \u3c 14 years were diagnosed with precursor B-cell ALL from January 1996 through June 2000. Of the 156 evaluable patients, 106 were treated with prednisone and 50 with dexamethasone. Fifty-two patients received steroids, L-asparaginase, and vincristine, whereas 104 high-risk patients received daunomycin in addition to these 3 agents. The incidence of gastritis was significantly higher among patients receiving dexamethasone (P = 0.01); incidence rates of hyperglycemia, hypertension, and myopathy were similar for all treatment groups. Dexamethasone led to more weight gain than did prednisone (+11.9% vs. +5.4%; P = 0.002). Serious infections were observed in 27 (25.5%) and 18 (36%) patients receiving prednisone and dexamethasone, respectively (P \u3c or = 0.2). Five patients, four of whom received prednisone and one of whom received dexamethasone, died of infection. The addition of daunomycin to treatment regimens increased overall toxicity (P \u3c 0.01). When daunomycin was included in treatment regimens, toxicity was greater among patients receiving dexamethasone; in contrast, when daunomycin was not included, toxicity was equal for both treatment groups. Regardless of daunomycin use, there was no difference in the incidence of serious infection between the two groups. ALL treatment was not compromised by steroid-related toxicity in either group.Conclusions: The addition of daunomycin led to a much larger increase in dexamethasone-related toxicity compared with the increase in prednisone-related toxicity. Although the use of daunomycin enhanced dexamethasone-related toxicity, this enhancement did not result in a higher mortality rate or the alteration of planned ALL therapy