Cengiz Canpolat

Cisplatin-Associated hemolytic uremic syndrome

Background. Hemolytic uremic syndrome (HUS) is an acquired disorder largely affecting infants and young children. It is characterized by the triad of microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia. Although its etiology is unknown, viral and bacterial infections, disseminated malignancies in adults, and a variety of chemotherapeutic agents including cisplatin, have been implicated in its occurrence. The association of HUS with chemotherapeutic agents after its detection in a pediatric patient treated with cisplatin is reviewed.

Pichia anomala fungaemia in immunocompromised children.

Pichia anomala is an emerging yeast causing serious nosocomial infections in newborn and immunocompromised children. We describe nosocomial port catheter infection due to P. anomala in three children who were receiving cancer chemotherapy, bloodstream infection in a preterm infant and in an infant with severe combined immunodeficiency. All patients were treated with amphotericin B. All isolates were susceptible to amphotericin B and fluconazole. No recurrence was observed during follow‐up in four of five patients. The common clinical feature in all of our patients was the presence of prior antimicrobial therapy.

Fibromyxoid sarcoma in a four-year-old child: case report and review of the literature.

We present a child with a rare and chemotherapy-resistant form of soft-tissue cancer, low-grade fibromyxoid sarcoma, first noted when he was 4 years old. He is the youngest patient reported to date. An 11-year-old white male presented to. The University of Texas M.D. Anderson Cancer Centers Department of Pediatrics with a 7-year history of right thigh mass and pulmonary nodules, confirmed on examination. He had undergone extensive prior chemotherapy and surgery. He received chemotherapy with high-dose cyclophosphamide (7 g/m2) and later etoposide (150 mg/m2/day x 5), with only slight shrinkage of the thigh mass and none in the lungs. Subsequently the tumor in his proximal thigh and his lung metastases were resected, and radiation therapy was administered to the thigh. His disease remained stable for 12 months, but he then developed a pleural-based metastasis on the left side and new bilateral lung metastases also. The tumors on the left side were removed; residual disease is stable after treatment for 6 months with subcutaneous alpha-interferon-2b. Low-grade fibromyxoid sarcoma is very uncommon in children. It grows slowly and metastasizes to distant organs, chiefly to the lungs. It is resistant to conventional chemotherapy, and thus far only surgery seems to have a life-prolonging effect. Newer chemotherapeutic and possibly biologic agents should be tried in future patients, in order to find an effective way to control the disease.

Clinical features and management of carboplatin-related hypersensitivity reactions in pediatric low-grade glioma.

PurposeThe effectiveness of carboplatin and vincristine chemotherapy in the treatment of low-grade glioma (LGG) is well established. However, carboplatin hypersensitivity reactions (CHR) are a major problem leading to premature cessation of therapy. We aimed to investigate the clinical features and the management strategies in CHR, retrospectively.MethodFifty LGG patients treated between October 1997 and January 2008 with carboplatin and vincristine were included in the study. Clinical features, management strategies, influence of demographic factors on CHR, and success rate in terms of continuation with carboplatin therapy were evaluated.ResultsCHR were observed in 20 (40%) patients and grade I reactions were the most common. The median number of carboplatin doses administered at the first episode of CHR was nine (range 1–41). Only younger age was found to be correlated with the presence of CHR. Nine patients had carboplatin desensitization protocol; eight patients were given various combinations of premedication while three had no modification. Treatment was terminated in five patients due to CHR. Overall success rate was 75%.ConclusionsThis is the largest single-center study conducted to investigate the frequency and the management strategies in patients with CHR who were treated with the same chemotherapy protocol for LGG. Premedication and desensitization were the preferred modifications in case of CHR. Overall, the success rate for carboplatin continuation is high in comparison to previous studies. Carboplatin can be continued successfully in many cases with CHR if reactions are managed in a timely fashion.

The effects of iron deficiency on neutrophil/monocyte apoptosis in children.

Abstract.  Objectives: Iron is essential for DNA synthesis; its deficiency may lead to impaired DNA synthesis and subsequent alterations in levels of apoptosis. Here, we have aimed to investigate effects of iron deficiency anaemia (IDA) on apoptotic response of phagocytic cells and to understand whether the effect is reversible after iron supplementation. Materials and methods: Forty‐nine IDA patients and 26 healthy controls, aged between 6 months and 12 years with similar demographic status, were considered. Neutrophil‐ and monocyte‐apoptotic responses of IDA patients and the control group were compared by flow cytometry. Then, IDA patients were provided with oral iron supplementation. On day 15 of iron therapy, neutrophil‐ and monocyte‐apoptotic responses of IDA patients were rechecked and were compared to those of control group. Results: Neutrophil‐ and monocyte‐apoptotic responses in terms of early and late percentages of apoptosis, and percentages of necrotic cells, were significantly less in IDA patients compared to the control group. The significantly low apoptotic responses of IDA patients rose to levels of the control group by day 15 of iron therapy. Besides, the effect of IDA on apoptotic responses was found to be more enhanced in severe IDA patients that those of mild IDA patients. Conclusion: Correction of differences after iron supplementation therapy implies that IDA might be a cause for changes in neutophil‐ and monocyte‐apoptotic responses. The impact of this diminution of apoptotic cellular function in IDA should be further investigated, with longitudinal studies, in order to document the impact of any severe and/or long‐lasting IDA on autoimmunity and malignancy.

False positivity of FDG-PET/CT in a child with Hodgkin disease

Role of Positron Emission Tomography (PET) with F‐18‐2‐fluoro‐2‐deoxy‐D‐glucose (FDG) in staging of Hodgkin disease is well established despite several controversies. We report a Stage III Hodgkin lymphoma patient with false positive FDG‐PET/CT results. Seven‐year‐old male with Hodgkin lymphoma was in remission at end of chemotherapy. At third and fourth month of postchemotherapy follow‐up, increased Gallium uptake and positive FDG‐PET/CT in right lower quadrant of abdomen was observed. Open biopsy revealed lymphoid hyperplasia. He has been followed for 21 months without any evidence of disease. Despite its documented benefit, we believe that results of FDG‐PET/CT should be interpreted with great caution in order to avoid unnecessary interventions. Pediatr Blood Cancer 2008;50:881–883.

Use of recombinant factor VIIa in a preterm infant with coagulopathy and subdural hematoma

Activated recombinant factor VIIa was administered to a preterm infant with bleeding diasthesis and a huge subdural hematoma that could not be controlled by the blood products. The coagulation tests were normalized the following day. Recombinant factor VIIa can be a choice in selected cases with intractable bleedings unesponsive to conventional replacement therapy.

Ifosfamide tolerance in osteosarcoma patients previously treated with cis-Diamminedichloroplatinum-II: Renal, hematologic, and neurologic observations

We attempted to ascertain renal, hematologic, and neurologic tolerance to ifosfamide (IFX) in pediatric patients previously treated with large single and cumulative doses of cis-Diamminedichloroplatinum-II (CDP) for osteosarcoma (OS). Twenty OS patients were treated with CDP: initially 150 mg/m2 was administered every 2 weeks for a maximum of seven courses. Later, other agents, including additional CDP, were also administered. Twelve patients were treated with intra-arterial CDP, one with intra-arterial, and later intravenous CDP, and seven with intravenous CDP. Patients who relapsed were treated with IFX. Renal function was monitored by measuring creatinine clearance, serum electrolytes, total protein, albumin and CO2 content, and urine analysis during IFX therapy. Prior to initiation of IFX, creatinine clearance was above 60 ml/min/m2 in all except one patient who had developed a hemolytic uremic syndrome (HUS). Cumulative CDP doses ranged from 300 to 22,500 mg/m2, and cumulative IFX doses 12 to 128 gm/m2. Myelosuppression was monitored by obtaining routine hemograms midway between each course of treatment. Neurologic tolerance was assessed by reviewing the medical records for any abnormality. The interval between CDP and IFX ranged from 1 to 64 months. All patients experienced a progressive reduction in creatinine clearance with CDP. The reduction in creatinine clearance, measured from base-line after three to four courses varied from 10 to 53.7%, after four to seven courses from 19 to 78%, and after seven courses from 12 to 80.5%. In all patients except five, including the HUS patient, creatinine clearance remained above 60 ml/min/m2 during IFX therapy. Twelve patients developed hypo-magnesemia in the vicinity of 1.4 to 1.6 mg/dl during CDP treatment and required magnesium supplementation. They were asymptomatic and the abnormality did not affect IFX tolerance. Fourteen patients intermittently displayed variable degrees of glycosuria, phosphaturia, and/or proteinuria during IFX therapy. This was considered to be a forma frustre type of Fanconis syndrome. Approximately 80% of courses of IFX were associated with reversible myelosuppression. No neurologic abnormalities were detected. The abnormalities detected during IFX treatment were not major, did not give rise to symptomatology, and did not require discontinuation of therapy. Renal abnormalities were considered a forma frustre type of Fanconis syndrome. Provided a creatinine clearance of 60 ml/min/m2 is accepted as a prerequisite for treatment, and no major preexisting renal disease is present, IFX is well tolerated by most patients previously exposed to very high cumulative doses of CDP.

Congenital disseminated malignant rhabdoid tumor of the soft tissue.

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Invasive respiratory aspergillosis is a treatable disease with early diagnosis and aggressive therapy.

This study aimed to document outcome of invasive respiratory aspergillosis (IRA) in pediatric malignancy patients. Patients with febrile neutropenia episodes followed between January 2003 and May 2007 were enrolled. Antifungal therapy was added to those who were still febrile on the 5th day of febrile neutropenia treatment. Patients were screened with computerized tomographies. IRA was identified in 22 of 98 patients. There were 13 males and the mean age was 97 months. Proven infection was established in 3, probable in 7, and possible in 12 patients. Liposomal amphotericin B was administered to all patients and was successful in 10 patients. Modifications with caspofungin or voriconazole were done in liposomal amphotericin B failures. The median duration of antifungal therapy was 5.5 months. The median follow-up time was 29 months. There was no evidence of IRA in 12 patients after completion of cancer chemotherapy. Six patients died due to underlying disease, whereas IRA was either in remission or stable disease. Four patients were lost due to IRA. The remission rate for IRA was 82%. Survival at 37 months was 55% (95% confidence ınterval 25–47 months). The amount of time that absolute neutrophil count after initiation of treatment for IRA remained at zero was found to be an independent prognostic factor on survival (P = .01). These results suggest that early diagnosis and aggressive treatment may increase the successful outcome of IRA.