Karin Tiedemann

ALK+ histiocytosis: a novel type of systemic histiocytic proliferative disorder of early infancy

We report 3 cases of a previously uncharacterized form of histiocytosis presenting in early infancy and showing ALK immunoreactivity. The patients presented with pallor, massive hepatosplenomegaly, anemia, and thrombocytopenia. Liver biopsy showed infiltration of the sinusoids by large histiocytes with markedly folded nuclei, fine chromatin, small nucleoli, and voluminous lightly eosinophilic cytoplasm that sometimes was vacuolated or contained phagocytosed blood cells. One patient developed cutaneous infiltrates that morphologically resembled juvenile xanthogranuloma. The histiocytes were immunoreactive for histiocytic markers (CD68, CD163, lysozyme), S100 protein, ALK (membranous and cytoplasmic pattern), and dendritic cell markers (fascin, factor XIIIa), but not CD1a and langerin. One case successfully analyzed by molecular techniques revealed TPM3-ALK fusion. Thus the spectrum of diseases exhibiting ALK translocation should be expanded to include ALK(+) histiocytosis. The disease in the 3 patients (2 having been given chemotherapy) resolved slowly over many months.

Estrogen as treatment of hemorrhagic cystitis in children and adolescents undergoing bone marrow transplantation.

Hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) can cause significant morbidity and mortality. Previous reports have suggested a role for estrogen in the control of HC in adult patients. Here, we describe the clinical courses of 10 children and adolescents treated with estrogen for HC following HSCT. Eight patients (80%) experienced a significant improvement in their hematuria following the commencement of therapy, with six (60%) undergoing resolution of macroscopic hematuria, without any recurrences. The treatment was well tolerated by the majority of patients, with only one patient needing to interrupt treatment (hepatotoxicity). We conclude that estrogen is well tolerated and often effective, and should be considered as an adjunctive treatment option in children and adolescents with HC following HSCT.

Sacrococcygeal teratoma: Has chemotherapy improved survival?

Case records of 57 patients (50 female, 7 male) with sacrococcygeal teratoma who were treated at the Royal Childrens Hospital in Melbourne between 1948 and 1986 were reviewed. There were 40 benign and 19 malignant tumors; two patients had malignant recurrence following excision of a benign tumor. The majority of the benign lesions were readily excised; 80% of these patients presented under the age of 6 months. In contrast, 16 of the 19 patients with malignant disease presented after 6 months of age and 12 of these died. Before 1975, malignant lesions were treated with surgery or irradiation, and in a few patients, single-agent chemotherapy. No patients survived. In 1976, intensive multiagent chemotherapy was introduced, with planned delayed surgical resection, with or without postoperative irradiation. Three of five patients treated between 1976 and 1980 survive disease-free and are almost certainly cured. Modern therapy is with cisplatin-containing regimens, and while initial responses in six patients with extensive disease are impressive, it is too early to evaluate the impact of these newer programs on cure.

Long-term follow-up and factors influencing outcomes after related HLA-identical cord blood transplantation for patients with malignancies: an analysis on behalf of Eurocord-EBMT

We analyzed risk factors influencing outcomes after related (R) human leukocyte antigen-identical cord blood transplantation (CBT) for 147 patients with malignancies reported to Eurocord-European Group for Blood and Marrow Transplantation. CBT has been performed since 1990; median follow-up was 6.7 years. Median patient age was 5 years. Acute leukemia was the most frequent diagnosis (74%). At CBT, 40 patients had early, 70 intermediate, and 37 advanced disease. CB grafts contained a median of 4.1 × 10(7)/kg total nucleated cells (TNCs) after thawing. The cumulative incidence (CI) of neutrophil recovery was 90% at day +60. CIs of acute and chronic graft-versus-host disease (GVHD) were 12% and 10% at 2 years, respectively. At 5 years, CIs of nonrelapse mortality and relapse were 9% and 47%, respectively; the probability of disease-free survival (DFS) and overall survival were 44% and 55%, respectively. Among other factors, higher TNCs infused was associated with rapid neutrophil recovery and improved DFS. The use of methotrexate as GVHD prophylaxis decreased the CI of engraftment. Patients without advanced disease had improved DFS. These results support banking and use of CB units for RCBT. Cell dose, GVHD prophylaxis not including methotrexate, and disease status are important factors for outcomes after RCBT.

Squamous Cell Carcinoma of the Tongue in a Child with Fanconi Anemia: A Case Report and Review of the Literature

This report documents a case of squamous cell carcinoma (SCC) of the tongue in a child with Fanconi anemia (FA). FA is an autosomal recessive syndrome defined by chromosomal breakage in response to diepoxybutane or mitomycin C in which many patients present with pancytopenia, hypoplastic bone marrow, hyperpigmentation of the skin, skeletal malformations, small stature, hypogonadism, and chromosomal aberrations. Such patients are prone to the development of hematological malignancies and squamous cell carcinoma, especially of the head and neck. Although FA appears to be genetically heterogeneous, all cases display abnormalities of DNA repair. A gene defective in one of the four subsets of FA patients has been defined. Defects in this gene are thought to play a role in the development of neoplasia in FA patients. However, many other factors may also contribute to the development of malignancies, including immune deficiencies, therapeutic strategies, and bone marrow transplantation. This report reviews the association of FA and SCC and highlights the many factors involved in the development of neoplasia within a single patient, including FA, cyclophosphamide, immunosuppression, X-irradiation, and chronic oral graft-versus-host disease. In addition, the human papillomavirus status, although negative, is documented for the first time in such a case.

Clinical outcome after percutaneous endoscopic gastrostomy in children with malignancies

Percutaneous endoscopic gastrostomies (PEG) are little‐used in pediatric oncology. We evaluated complications and efficacy of PEGs in children with malignancies in a retrospective case series. Outcome measures were infection and weight gain. Sixteen PEGs were inserted in 14 patients (mean age 10.3 years; SD 5.6). Sixteen wound infections occurred in nine children (3.7 episodes/1,000 days). Mean weight‐for‐age z‐score fell from diagnosis to PEG placement (−0.68 (SD 1.2) to −1.32 (SD 1.26); P < 0.001) but stabilized afterward. Two (12%) were removed early. PEG placement reversed early weight loss and infectious complications did not usually lead to early PEG removal. Pediatr Blood Cancer 2011;56:1146–1148.

Outcomes of haematopoietic stem cell transplantation for inherited metabolic disorders: a report from the Australian and New Zealand Children's Haematology Oncology Group and the Australasian Bone Marrow Transplant Recipient Registry.

We report a retrospective analysis of 53 haematopoietic stem cell transplants for inherited metabolic disorders performed at ANZCHOG transplant centres between 1992 and 2008. Indications for transplant included Hurler syndrome, ALD, and MLD. The majority of transplants utilized unrelated donor stem cells (66%) with 65% of those being unrelated cord blood. Conditioning therapy was largely myeloablative, with Bu plus another cytotoxic agent used in 89% of recipients. Primary graft failure was rare, occurring in three patients, all of whom remain long‐term survivors following the second transplant. The CI of grade II‐IV and grade III‐IV acute GVHD at day +100 was 39% and 14%, respectively. Chronic GVHD occurred in 17% of recipients. TRM was 12% at day +100 and 19% at one yr post‐transplant. OS at five yr was 78% for the cohort, 73% for patients with ALD and 83% for patients with Hurler syndrome. There was no statistically significant difference in overall survival between unrelated marrow and unrelated cord blood donor groups. The development of interstitial pneumonitis was an independent variable shown to significantly impact on TRM and OS. In summary, we report a large cohort of patients with inherited metabolic disorders with excellent survival post‐allogeneic transplant.

Diagnosis of gastrointestinal graft-versus-host disease--is rectal biopsy enough?

Graft‐versus‐host disease (GVHD) is an important cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). The clinical diagnosis of gastrointestinal GVHD can be difficult to establish and endoscopic diagnosis entails a procedural risk. The aim of this study was to determine whether rectal biopsy alone might be sufficient to establish or exclude the diagnosis of intestinal GVHD.

Progressive emergence of an oseltamivir-resistant A(H3N2) virus over two courses of oseltamivir treatment in an immunocompromised paediatric patient

A minor viral population of oseltamivir‐resistant A(H3N2) viruses (E119V neuraminidase mutation) was selected and maintained in a continually infected immunocompromised child following initial oseltamivir treatment. A subsequent course of oseltamivir given 7 weeks later rapidly selected for the E119V variant resulting in a near‐pure population of the resistant virus. The study highlights the challenges of oseltamivir treatment of immunocompromised patients that are continually shedding virus and demonstrates the ability of the E119V oseltamivir‐resistant virus to be maintained for prolonged periods even in the absence of drug‐selective pressure.

Experience with high dose multiagent chemotherapy and autologous bone marrow rescue in the treatment of twenty-two children with advanced tumours

Intensive chemotherapy followed by infusion of cryopreserved autologous bone marrow (ABMR) was used in the treatment of 22 children with advanced tumours. In nine this was their initial therapy; in eight it was used after partial or complete remission had been achieved with standard therapy; and in five, after relapse had occurred. Recovery of marrow function occurred in 20 patients with a mean time of 13.2 and 18.2 days to recovery of neutrophils (>0.5 × 109/t) in newly diagnosed and previously treated patients respectively. Platelet count recovery to >50 × 109/l occurred in a mean time of 13.4 days in newly diagnosed and 20.4 days in previously treated patients.