Talia Ileri

Chemotherapy for Myeloid Malignancy in Children With Fanconi Anemia

Children with Fanconi anemia (FA) have a markedly increased risk of developing myeloid malignancies. Historically, patients with FA and myeloid malignancy have extremely poor outcomes. There are currently no clinical trials or case series addressing the use of chemotherapy for children with FA, except in the context of preparative regimens for stem cell transplantation (SCT). In this report we describe the toxicity of a chemotherapy approach for patients with FA and myeloid malignancy to achieve cytoreduction prior to SCT.

Prospective evaluation of acute and chronic renal function in children following matched related donor hematopoietic stem cell transplantation

Ileri T, Ertem M, Ozcakar ZB, Ince Unal E, Biyikli Z, Uysal Z, Ekim M, Yalcinkaya F. Prospective evaluation of acute and chronic renal function in children following matched related donor hematopoietic stem cell transplantation.
Pediatr Transplantation 2010: 14: 138–144.

EXTRAMEDULLARY HEMATOPOIESIS WITH SPINAL CORD COMPRESSION IN A CHILD WITH THALASSEMIA INTERMEDIA

Spinal cord compression due to extramedullary hematopoiesis is an extremely rare complication of thalassemia intermedia. No cases with this complication have been reported in the first decade of life, because masses of heterotropic marrow developed in patients as a result of continuous erythropoiesis. We report the 9-year-old patient suffering from thalassemia intermedia and presenting spinal cord compression. We also review the literature about treatment options, because there is no consensus about the optimal treatment of these patients. Our patient was successfully treated with radiation therapy followed by hydroxyurea. With this combination therapy, he had no recurrence during the 4-year follow-up period. Clinical awareness of this phenomenon with the early treatment is essential for optimizing the successful outcome.

Blood group genotyping in multi-transfused patients

BACKGROUND In chronically transfused patients, the classical hemagglutination assays may be inaccurate in defining the RBC phenotypes of the patients due to previous transfusions. DESIGN DNA samples from 39 multi-transfused patients including thalassemia and sickle cell disease were used for red blood cell genotyping. The Rh-Type and KKD-Type (BAGene, BAG Healthcare) were used to determine the polymorphisms associated with antigen expression for RHD, RHCE and Kell, Kidd, Duffy blood group systems, respectively. Results were compared with previously determined phenotyping results for RhD, RhCcEe and Kell by hemagglutination method. RESULTS Nineteen out of the 37(51%) patients had discrepancies between genotyping and phenotyping results in a total of 25 alleles. In 12 patients, the discrepancies had the potential of alloimmunization. CONCLUSION Blood group genotyping has vital importance in transfusion management of chronically transfused patients especially if the patients were not phenotyped before starting the initial transfusions.

Voriconazole-induced QT interval prolongation and torsades de pointes

The QT interval of the electrocardiogram (ECG) represents myocardial depolarization and repolarization. Prolongation of the QT interval corrected for heart rate (QTc interval) may result in life-threatening arrhythmias, such as polymorphous ventricular tachycardia (VT) of the torsades de pointes (TdP) type and ventricular fibrillation. 1 Long QT syndrome, sympathetic activation, sleep, marked bradycardia, a long list of certain drugs, hypocalcemia, hypokalemia, hypomagnesemia, myocarditis, diffuse myocardial disease, cerebrovascular injury, autonomic neuropathy, arsenic, organophosphates, severe malnutrition and HIV may prolong the QT interval. QTc interval is calculated using Bazett’s formula and should not exceed 440 ms except in infants. 1

Related donor hematopoietic stem cell transplantation for Fanconi anemia without radiation: A single center experience in Turkey

Abstract:  Eight children with FA underwent allogeneic HSCT without using irradiation for the conditioning regimen. Patients received two different conditioning regimens: first two patients received BU 1.5 mg/kg/day for four days and CY 10 mg/kg/day for four days and the other regimen was: Flu 30 mg/m2/day for five days, CY 10 mg/kg/day for two days, and ATG‐Fresenius 9–10 mg/kg/day for four days. GVHD prophylaxis consisted of CsA + MTX for the first two patients and only CsA for the others. All patients received HLA‐identical stem cells from related donors. Primary engraftment was demonstrated in all patients. No patient developed acute GVHD and one patient had chronic GVHD. Only one patient who received BU based regimen died because of VOD. Overall, seven patients (87.5%) are alive with stable full donor chimerism at a median follow‐up time of 2.5 yr (range: 1.7–8.9 yr). None of the patients developed secondary malignancy. Based on our data, we conclude that Flu‐based, non‐irradiation conditioning regimen was safe with low organ toxicity and stable engraftment in FA patients undergoing HSCT from matched related donors.

Primary adrenal insufficiency in a child after busulfan and cyclophosphamide-based conditioning for hematopoietic stem cell transplantation.

Abstract High rates of skeletal complications, growth disturbances, thyroid and gonadal dysfunction have been described in children undergoing stem cell transplantation. Although secondary adrenal insufficiency has been diagnosed, no primary adrenal insufficiency has been reported after busulfan and cyclophosphamide (Bu/Cy)-based conditioning regimens for stem cell transplantation in children. A 9-year-old girl with myelodysplastic syndrome was treated with stem cell transplantation of allogeneic origin. She received myeloablative conditioning chemotherapy, Bu and Cy. Her serum cortisol level was normal before stem cell transplantation. Then, 17 months after stem cell transplantation, chronic graft-versus-host disease developed and was treated with methyl prednisolone for 3 months. The control endocrinological investigation revealed low serum cortisol and high serum adrenocorticotropin (ACTH) levels 6 months after completion of methyl prednisolone treatment. The ACTH stimulation test demonstrated primary adrenal insufficiency, and the other etiologies of primary adrenal insufficiency were excluded. The patient received oral prednisolone replacement therapy. She was followed-up for 44 months and required increases in steroid doses during stress periods. Primary adrenal insufficiency which was observed in our patient after Bu/Cy-based conditioning regimen for stem cell transplantation has not been reported in children and adrenal function should be closely monitored in these patients both before stem cell transplantation and after stem cell transplantation.

Significant loss of hepatitis A Ab after allogeneic hematopoietic SCT in pediatric patients.

Loss of specific immunity after hematopoietic SCT (HSCT) is well documented for polio, measles, mumps and tetanus. There are limited studies reporting the loss of Hepatitis A virus immunity and no reports evaluating the effect of donor immunity on Hepatitis A virus (HAV) immunity loss after HSCT. A total of 49 of the 81 patients who received HSCT at the Ankara University Pediatric HSCT Unit from January 1997 to December 2006 had HAV serology tested before HSCT and were evaluated for seroprevalence, and 30 of 49 patients were evaluated for the loss of Ab and for the effect of donor immunity on the loss of HAV Abs. The seroprevalence before HSCT was 75.5%. Loss of Ab was detected in 43.5% (10/23) of the patients. The median time to loss of Ab was 12 months (12–32 months), and 60% of these patients were seronegative at 12 months after HSCT. After HSCT, 46.7% of the patients were seronegative. Loss of Ab was higher in the seronegative donor group (75 vs 26%). The loss of HAV Ab is high after allogeneic HSCT for pediatric patients. Reimmunization should be considered for the continuation of individual and community immunity. Further studies with larger study groups are warranted to clarify the role of donor immunity on the loss of HAV immunity.

Reversible myelofibrosis associated with hemophagocytic lymphohistiocytosis

To theEditor:A 16-year-old femalewas referred to our center for fever, anemia, neutropenia, and thrombocytopenia. Her liver and spleen were not palpable. Biochemistry tests were significant for elevated lactate dehydrogenase and mildly elevated serum aspartate aminotransferase. Viral serologic studies were found to be negative. Tomography examination of the head, thorax, abdomen, and pelvis did not reveal any signs suggestive of infection. Treatment with broad-spectrum antibiotics was started. Bone marrow (BM) aspiration and biopsy were performed. Megakaryocyte, fat cell and dysplastic changing were not observed on the biopsy. Although she was on broad spectrum antibiotics, she had persistent fever, and hepatosplenomegaly 10 days after her hospitalization. Fifteen days after, her lung sounds were decreased at both lung bases and chest tomography examination showed that pericardial effusion and pneumonic infiltration at both lung bases. At this time, M. pneumonia specific PCR of blood was determined to be positive two times. On day 40, she developed hepatomegaly. Several BM biopsies did not showevidence for neoplasia. BMaspirations did not reveal sufficient material, and all BM biopsies showed reduced hematopoiesis and marked increased reticulin fibers (Fig. 1A). She was diagnosed with myelofibrosis on the basis of these biopsy results. Further laboratory analyses were performed but all of them failed to demonstrate the etiology of myelofibrosis. The fourth BM aspiration material was mildly hypocellular, and hemophagocytic histiocytes were present. She had persistant fever, pancytopenia, hepatosplenomegaly, hypertriglyceridemia, and hyperferritinemia. These findings indicated BM fibrosis associated with hemophagocytic lymphohistiocytosis (HLH). After treatment according to the HLH 94 chemotherapy protocol was initiated, the hepatosplenomegaly decreased and the blood cell counts improved. After the first positive PCR of M. pneumonia result, administration of clarithromycin was started, but no improvement was seen. Treatment with oral doxycycline was used concurrent with initiation of HLH 94 chemotherapy, resulting in a rapid and complete clinical improvement within 3 weeks. Six months after completion of chemotherapy, laboratory tests revealed normal hematological and biochemical parameters. The results of PCR of M. pneumonia were negative in blood and BM after recovery. BM aspirations were normocellular with no increased reticulin fibers and hemophagocytosis (Fig. 1B). Serum levels of immunoglobulin subclasses were normal. Two years after treatment completion, she remained healthy off therapy. HLH is characterized by a systemic activation of macrophages which are induced to phagocytose of hematopoietic elements [1,2]. Marrow fibrosis can be a polyclonal reaction to inflammatory mediators generated by the transformed clone [3,4]. In our case, the findings might have been induced by HLH because no predisposing factors were identified despite detailed inquiry. The lack of clinical evidence for extramedullary hemotopoiesis was striking; these findings suggest that reversiblemyelofibrosis can be associatedwith HLH. The relationship to the mycoplasma infection is unclear but may be associated well [5,6,7].

A breast-fed newborn with megaloblastic anemia-treated with the vitamin B12 supplementation of the mother.

Pregnant women with low B12 levels are unable to provide the necessary amount of this vitamin to their fetuses. The mothers are usually not anemic, and failure to thrive and neurologic deficits are more common in their infants than in megaloblastic anemia. We report the case of a newborn that was born to a vegetarian mother and presented with the symptoms of megaloblastic anemia at birth; we also discuss vitamin B12 metabolism during pregnancy and lactation. An interesting feature of the present case is that it is the only reported case of a newborn that was treated by supplementation of the mother.