Pearson marrow pancreas syndrome in patients suspected to have Diamond-Blackfan anemia.

Pearson marrow pancreas syndrome (PS) is a multisystem disorder caused by mitochondrial DNA (mtDNA) deletions. Diamond-Blackfan anemia (DBA) is a congenital hypoproliferative anemia in which mutations in ribosomal protein genes and GATA1 have been implicated. Both syndromes share several features including early onset of severe anemia, variable nonhematologic manifestations, sporadic genetic occurrence, and occasional spontaneous hematologic improvement. Because of the overlapping features and relative rarity of PS, we hypothesized that some patients in whom the leading clinical diagnosis is DBA actually have PS. Here, we evaluated patient DNA samples submitted for DBA genetic studies and found that 8 (4.6%) of 173 genetically uncharacterized patients contained large mtDNA deletions. Only 2 (25%) of the patients had been diagnosed with PS on clinical grounds subsequent to sample submission. We conclude that PS can be overlooked, and that mtDNA deletion testing should be performed in the diagnostic evaluation of patients with congenital anemia.

A clinical algorithm identifies high risk pediatric oncology and bone marrow transplant patients likely to benefit from treatment of adenoviral infection.

BACKGROUND: Adenoviral infections cause morbidity and mortality in blood and marrow transplantation and pediatric oncology patients. Cidofovir is active against adenovirus, but must be used judiciously because of its nephrotoxicity and unclear indications. Therefore, before introducing cidofovir use during an adenoviral outbreak, we developed a clinical algorithm to distinguish low risk patients from those who merited cidofovir therapy because of significant adenoviral disease and high risk for death. OBJECTIVE: This study was conducted to determine whether the algorithm accurately predicted severe adenovirus disease and whether selective cidofovir treatment was beneficial. STUDY DESIGN: A retrospective analysis of a pediatric oncology/blood and marrow transplantation cohort prealgorithm and postalgorithm implementation was performed. RESULTS: Twenty patients with adenovirus infection were identified (14 high risk and 6 low risk). All low-risk patients cleared their infections without treatment. Before algorithm implementation, all untreated high-risk patients died, 4 out of 5 (80%), from adenoviral infection. In contrast, cidofovir reduced adenovirus-related mortality in the high-risk group postalgorithm implementation (9 patients treated, 1 patient died; RR 0.14, P<0.05) and all treated high-risk patients cleared their virus. CONCLUSIONS: The clinical algorithm accurately identified patients at high risk for severe fatal adenoviral disease who would benefit from selective use of cidofovir.

Successful treatment of a child with late-onset T-cell post-transplant lymphoproliferative disorder/lymphoma.

We report a novel regimen for refractory post-transplant T-cell lymphoma (PTL). Our patient presented with non-Epstein-Barr virus (EBV) related, T-cell post-transplant lymphoproliferative disease (PTLD) 3.5 years after liver transplantation. Initially diagnosed as polyclonal PTLD, the disease progressed to a monoclonal, T-cell PTL that was refractory to several chemotherapy regimens but responded to a regimen consisting of fludarabine, cyclophosphamide, cytarabine, and alemtuzumab. Consolidation therapy included high-dose chemotherapy, autologous hematopoietic stem cell rescue, and radiation therapy. She remains in remission 2.5 years later. T-cell PTL is a rare disease with a poor prognosis; this regimen provides a novel, potentially curative approach for its treatment.

Bone marrow engraftment analysis after granulocyte transfusion.

We present the case of a 6-year-old male who received an allogeneic bone marrow transplant as part of treatment for acute lymphoblastic leukemia. The patient relapsed 5 months after transplantation and received additional chemotherapy. He acquired an angioinvasive fungal infection that required transfusion of granulocytes. Approximately 5 weeks after relapsing (181 days after transplant), a bone marrow specimen was taken for molecular engraftment analysis and flow cytometry to assess graft loss as well as residual disease. The engraftment results generated by the multiple short tandem repeat loci tested were inconsistent, and alleles were present at several loci that were of neither patient nor donor origin. An error in specimen identification was initially considered. Further investigation into the circumstances surrounding procurement of the patient's bone marrow aspirate revealed that the patient had received a granulocyte transfusion approximately 10 hours before the bone marrow specimen was taken. In addition, morphological and flow cytometric analyses of the same bone marrow aspirate demonstrated a significant degree of peripheral blood contamination. We determined that the unknown alleles in the bone marrow engraftment specimen were derived from the donor of the transfused granulocytes. This case illustrates that white cell transfusion can lead to erroneous bone marrow engraftment results, particularly if only one microsatellite locus is used to monitor engraftment.

Treatment of hepatitis-associated aplastic anemia with high-dose cyclophosphamide.

OBJECTIVE: Demonstrate that high-dose cyclophosphamide (CY) is effective therapy for hepatitis-associated aplastic anemia (HAA). BACKGROUND: HAA is a sequence of seronegative hepatitis followed by aplastic anemia. Optimal treatment is matched-sibling allogeneic bone marrow transplantation (BMT). The combination of antithymocyte globulin (ATG) and cyclosporine (CSA) has also been studied, but there are scarce data regarding treatment of HAA. PROCEDURE: Five patients (median age 14 years; range 6-17 years) with HAA and without an HLA-matched sibling were treated with high-dose CY (50 mg/kg/day IV x 4 days) followed by granulocyte-colony stimulation factor (G-CSF). RESULTS: After at least 1 year of follow-up, four of five patients are in remission without further immune suppression beyond high-dose CY. Of the 4 responders, median time to absolute neutrophil count (ANC) >500 microl(-1) was 51 days (range 44-369). Median time to transfusion independence for erythrocytes and platelets was 109 (range 57-679) and 160 (range 48-679) days, respectively. The fifth patient did not respond and proceeded to an unrelated donor transplant. One patient met criteria for autoimmune hepatitis (AIH) in addition to HAA. In this case, high-dose CY successfully induced remission of both diseases. CONCLUSIONS: High-dose CY induces durable remissions in HAA and may be an effective treatment for AIH.

Chronic graft versus host disease.

The ability to cure increasing numbers of individuals for malignant and non-malignant diseases with the use of stem cell transplantation has resulted in a growing number of long-term survivors with unique medical issues. Chronic graft versus host disease (GvHD) continues to be a significant problem in the allogeneic stem cell transplant setting and, as we continue to use alternative stem cell sources and attempt to modulate the immune system to increase an anti-tumour effect, we will probably see rising numbers of patients with this complication. The capacity to treat this problem and improve both the immediate quality of life as well as long-term effects is imperative and requires the ability of haematologists/oncologists to identify chronic GvHD and its multi-organ system presentations. We describe the risk factors for developing chronic GvHD, its presentation and the current treatment options for both initial therapy and secondary treatment.

Misinterpretation of a Calvert-derived formula leading to carboplatin overdose in two children.

Carboplatin is currently recommended to be dosed according to renal function. In adults, dosing by the Calvert formula is based on evidence that carboplatin clearance closely parallels glomerular filtration rate. Several studies have attempted to validate the Calvert formula and its derivations in pediatrics, but no final consensus has been achieved. As a result, different versions of the original formula exist in the pediatric literature. Other factors may also contribute to confusion when applying the formula to young patients, including the manner in which renal function is measured and reported. We describe how misinterpretation of the Calvert formula resulted in carboplatin overdosing in 2 pediatric patients with high-risk neuroblastoma undergoing peripheral blood stem cell transplantation. Measures to avoid such errors have been instituted.