PREVENTION OF RED CELL DEHYDRATION: A POSSIBLE NEW TREATMENT FOR SICKLE CELL DISEASE

One of the pathogenetic mechanisms responsible for sickling of erythrocytes in patients with sickle cell disease is the decreased hydration status of the cells. In this brief review, we discuss the pathophysiologic background and explore some new treatment options to prevent vaso-occlusive crises or other problems in this patient population.     

HODGKIN'S DISEASE IN A CHILD WITH SICKLE CELL DISEASE TREATED WITH HYDROXYUREA

Hydroxyurea (HU) is an oral drug that ameliorates the clinical course of sickle cell anemia by &#175 increasing the levels of fetal hemoglobin and decreasing the adhesion of red cells to endothelium. Although HU has minimal short-term toxicity, few data are available about the long-term safety and the potential risk for carcinogenesis or leukemogenesis. An 8-year-old child with sickle cell / &#103 0- thalassemia who received HU treatment for painful crises is described. Six months after the initiation of the HU treatment he developed Hodgkin's disease, lymphocyte predominance subtype. Chemotherapy induced a complete remission. After discontinuation of chemotherapy the painful crises recurred and bone marrow transplantation was decided at the age of 12 years. Two years after the bone marrow transplantation, the child is in complete remission without painful crises. Although the authors suggest that the development of Hodgkin's disease is a coexisting event, questions arise about the safety of HU treatment in childhood.     

PNEUMOMEDIASTINUM,SUBCUTANEOUS EMPHYSEMA,AND PULMONARY FIBROSIS IN A PATIENT WITH IDIOPATHIC PNEUMONIA SYNDROME AFTER BONE MARROW TRANSPLANTATION

An adolescent female underwent bone marrow transplantation for relapsed leukemia and developed acute and chronic graft-versus-host disease and idiopathic pneumonia syndrome. Her lung disease responded to large doses of methylprednisolone but evolved to pulmonary fibrosis and pneumomediastinum and subcutaneous emphysema in the convalescent period. Pulmonary function tests revealed a restrictive pattern. Pneumomediastinum and subcutaneous emphysema are complications not only of obstructive but also of restrictive lung disease and vary with respect to time of onset.     

THE ROLE OF RIB INFARCTS IN THE ACUTE CHEST SYNDROME OF SICKLE CELL DISEASES

The acute chest syndrome is a generic term for pulmonary complications of sickle cell diseases with heterogeneous etiologies that include pneumonia, vaso-occlusion of pulmonary arterioles, rib infarction, and fat embolism syndrome. My review summarizes these etiologies, the evidence, and pathophysiology supporting the hypothesis that infarction of segments of ribs by the same vaso-occlusive process responsible for the acute episodes of pain (characteristic of the sickle cell diseases) is often involved in the acute chest structure. Inflammation associated with the infarct then causes splinting, hypoventilation, and hypoxia and further vaso-occlusion. The relationship with adult respiratory distress syndrome and fat embolism is also discussed. Use of the incentive spirometer combined with effective analgesia when chest pain is present is advocated for prevention of the pulmonary infiltrates. Newer understanding of the role of nitric oxide in regulating oxygen transport and its relationship to blood transfusions used in therapy of the acute chest syndrome are discussed.     

VENOUS THROMBOEMBOLISM, FACTOR V LEIDEN, AND METHYLENETETRAHYDROFOLATE REDUCTASE IN A SICKLE CELL ANEMIA PATIENT

Vaso-occlusive crisis is the most common cause of morbidity in patients with sickle cell anemia (SCA). Central nervous system involvement that leads to hemiplegia is the most frequent neurological complication in those patients. Peripheral deep venous thromboembolism was not reported in SCA patients. Activated protein C resistance is associated with an increased risk of thrombophilia. The authors report an SCA patient with recurrent cerebrovascular accident and deep venous thrombosis. Activated protein C resistance due to factor V Leiden heterozygous and heterozygocity for the methylenetetrahydrofolate reductase were diagnosed and suspected to be the risk factors that contribute to the development of the deep vein thrombosis in this SCA patient.     

DOUBLE HAPLOIDENTICAL TRANSPLANTATION OF HEMATOPOIETIC PROGENITOR CELLS IN A BOY WITH MYELODYSPLASTIC SYNDROME

A 12-year-old boy with myelodysplastic syndrome underwent a double transplantation of hematopoietic progenitor cells from his haploidentical brother. After conditioning with busulfan, cyclophosphamide, and Vepesid, the first bone marrow transplantation was performed using 3.53 10 6/kg of CD34+ cells. Initial engraftment was followed by graft rejection. The second conditioning consisted of melphalan and anti-thymocyte globulin. The boy was then transplanted with 5.15 10 6/kg of CD34+ cells, harvested from bone marrow (BM) and peripheral blood. Graft versus host disease (GvHD) prophylaxis consisted of cyclosporine A+ short methotrexate. Hematological recovery was rapid and stable. Acute GvHD I (skin) resolved after 2 weeks of steroid treatment. A relapse occurred on day + 140. At that time NK cells decreased from 20 to 7% with the lowest CD4+/CD8+ratio, 0.07. Just after relapse, the percentage of cytokine-induced killer cells (CIK-CD3+CD56+)dropped from 3.34 to 0.1%. CsA treatment was stopped and the patient received T cell (CD3+cells)add-back four times on days +146, + 199, + 234, and + 262 in doses of 0.5 10 5,1.0 105,2.0 105, and 4.0 105/kg, respectively. No acute GvHD occurred. Additionally, bone marrow biopsy before the second add-back showed complete remission. Analysis of lymphocyte subsets before the fourth add-back showed the highest values of CD4+, NK, and CIK cells and also the highest CD4 + /CD8 + ratio.     

TREATMENT OF CHILDHOOD ACUTE MYELOGENOUS LEUKEMIA WITH ALLOGENEIC AND AUTOLOGOUS STEM CELL TRANSPLANTATION DURING THE FIRST REMISSION: A Report from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan

Hemophilic pseudotumor is an uncommon complication seen in approximately 1–2% of patients with severe hemophilia. Hemophilic pseudotumors are distinguished into two subdivisions based on location, proximal or distal. Plain x-rays and CT are useful in diagnosis, but MR imaging is the diagnostic test of choice because of its sensitivity to the various blood products. The choice of therapy depends on many parameters, such as the size of the tumor, the age of the patient, and the relation with underlying organs. In most cases of asymptomatic hemophilic pseudotumor, conservative treatment with administration of missing factor as well as immobilization is recommended. The authors describe a 13-year-old boy with severe hemophilia A, who presented with a tibial pseudotumor a few months after an injury. He was conservatively treated for a long period, with daily administration of recombinant factor VIII. His clinical condition improved shortly after therapy induction, but radiological improvement has been moderate. Case history, imaging findings, and therapeutic options are discussed.