Eva Radel

Thrombocytopenic purpura with infectious mononucleosis: Report of 2 cases and a review of the literature

Thrombocytopenic purpura is a rare complication of infectious mononucleosis. It is of importance to pediatricians, because it may be confused with acute leukemia. Two children who presented with purpura, lymphadenopathy, and hepatosplenomegaly as manifestations of infectious mononucleosis are reported. The literature is reviewed and the fifferential diagnosis is discussed. The current status of adrenocortical steroids in the treatment of this complication as well as in infectious mononucleosis in general is also reviewed.

Treatment of pediatric ocular melanoma with high-dose interleukin-2 and thalidomide.

Uveal melanoma is the most common primary ocular malignancy, although it is rare in children, and patients presenting with metastatic disease have a median survival of only 2 to 5 months. The tumor is generally unresponsive to systemic chemotherapy, but immunotherapy may be effective in selected patients. This report describes an 8-year-old girl with metastatic uveal melanoma treated with high-dose, bolus interleukin-2 (IL-2) and the antiangiogenic agent thalidomide. She tolerated treatment well and initially responded with stable disease in the liver and pancreas for 23 months. New pulmonary metastases developed and she was re-treated with high-dose IL-2, resulting in regression of her liver lesions and stable pulmonary disease for more than 18 months. These results suggest that IL-2 at high doses, and in combination with thalidomide, may be useful for uveal melanoma with tolerable side effects in children. Further study of this combination in children with immune-responsive tumors is warranted.

TRANSFUSION THERAPY AND ITS COMPLICATIONS IN PATIENTS WITH COOLEY'S ANEMIA.

Transfusion therapy on a continuing basis remains the major form of treatment for patients with Cooley’s anemia. In addition to the long-term complications of iron-overloading, there are many more immediate problems associated with multiple transfusions. This discussion will be limited to the transfusion therapy of thalassemia, and the untoward reactions which may occur during or shortly after blood administration. In order to obtain a reasonably large conglomerate of experience a number of treatment centers were polled. More than a dozen centers, caring in all for more than 150 patients with Cooley’s anemia responded.* Indications for Transfusion As a result of our inquiry it is evident that there are no clearly define-? criteria for determining when a child with thalassemia should be given blood. Transfusion is generally performed either when a specific hemoglobin level is reached, or when the patient becomes symptomatic. In those centers where blood is administered on symptomatic indication, the pretransfusion hemoglobin is frequently between 3.0 and 6.0 gm. per 100 ml. Where a specific hemoglobin concentration has been chosen as a guide, the level chosen is usually between 5.0 and 7.0 gm. per 100 ml. The usual interval between transfusions is three to six weeks. It has been our routine to determine for each patient the hemoglobin level at which symptoms such as anorexia, fatigue, listlessness, irritability, headache, or bone pain appear, and to transfuse a t a level one gm. per cent above this value. In our experience, one or more symptoms appear at hemoglobin levels below 6.5 gm. per 100 ml. and usually we have transfused children with Cooley’s anemia a t hemoglobin concentrations between 6.5 and 7.5 gm. per 100 ml. It is our strong opinion that there is no advantage, and potential disadvantage, to transfusing children only after symptoms appear. We prefer not to have the children undergo alternating periods of normal and subnormal activity, accompanied by varying degrees of a sense of illness. We have observed that some parents in their anxiety to increase the period between transfusions, delay in reporting the onset of symptoms, and in bringing the child to the clinic, resulting in fairly severe degrees of malaise and irritability for a week or more in every month. Three years ago, when we admitted two newly diagnosed infants to our clinic, we decided to t ry a rather different regimen. We have maintained

Lymph node manifestations of limited Churg-Strauss syndrome.

Churg–Strauss syndrome is a systemic vasculitis characterized by asthma, tissue and blood eosinophilia, and granulomatous vasculitis. Lymph node involvement as part of systemic disease or as the primary site of involvement is rare. We report a single case of primary (isolated) nodal Churg–Strauss syndrome occurring in an 11-year-old boy with asthma, fever, night sweats, and cervical adenopathy. The clinical diagnosis was lymphoma. The unusual presentation of Churg–Strauss syndrome limited to lymph nodes is important to recognize and diagnose correctly because the administration of steroid therapy is associated with a favorable outcome.

Needle Biopsy in the Diagnosis of Testicular Leukemia in Children

Aggressive chemotherapy in patients with acute lymphoblastic leukemia has resulted in a marked upsurge in patient survival. In the course of their management, testicular biopsy and rebiopsy have an important role. We evaluated the histological findings in 50 sets of open wedge and simultaneous needle core biopsy specimens from 44 testes of children with acute lymphoblastic leukemia to determine the accuracy of the needle biopsy technique in the evaluation of testis involvement in acute lymphoblastic leukemia. We conclude that needle biopsy of the testis in acute lymphoblastic leukemia is highly accurate and correlates well with the conventional open wedge biopsy, and it may have a role in the management of children with acute lymphoblastic leukemia.

Characterization of t(11;19)(q23;p13.3) by fluorescence in situ hybridization analysis in a pediatric patient with therapy-related acute myelogenous leukemia

This case presents a Caucasian girl diagnosed with early pre-B cell acute lymphoblastic leukemia at age 2 years. The only chromosomal anomaly detected in her bone marrow cells at this time was an add(12p). By age 4 years, she had a bone marrow and central nervous system (CNS) relapse of ALL and was treated with chemotherapy that included etoposide. She was in complete remission for 2 years following chemotherapy with etoposide, but later developed therapy-related acute myeloid leukemia (t-AML). At this time, a t(11;19)(q23;p13.3) rearrangement was detected in her bone marrow cells. The AML relapsed again 1 year after allogeneic bone marrow transplant (BMT). The presence of a chromosome 11 abnormality involving band 11q23 in this patient suggests that the transformation from ALL to t-AML was a consequence of etoposide included in her chemotherapy. Studies have shown that the 11q23 breakpoint in the t(11;19) rearrangement is consistent, and involves the MLL gene in t-AML patients. However, the breakpoint in 19p is variable in that it could be located either at 19p13.1 or 19p13.3 and thus could involve either of two genes: ELL (11-19 lysine-rich leukemia gene) on 19p13.1 or ENL (11-19 leukemia gene) on 19p13.3. In this study, the t(11;19)(q23;p13.3) was further characterized and the breakpoint regions were defined by fluorescence in situ hybridization (FISH) analysis.

SELECTIVE MICROVASCULAR TRAPPING OF SICKLED CELLS

A decrease in sickled cells is seen during painful crisis in some patients with sickle cell anemia. This may be due to a selective trapping of sickled cells at the sites of vaso-occlusion. To explore this possibility further, an animal model was utilized. Rats with jugular vein catheters were transfused with sickle blood(SB) saturated with carbon monoxide (CO) to yield an in vivo CO saturation of 20 to 2

848 HYPOCALCEMIA IN THALASSEMIA MAJOR

%. The rats were exposed to 100% O2 to eliminate the CO, and then to 7% O2. The mean survival of SB rats in 7% O2 (39±21 min.[20]) was significantly shorter than that of rats transfused with normal human blood (128±55 min.[20]). Survival of SB rats subjected to hypoxia without prior exposure to 100% O2 was 84±32 min.[l6]. This improved survival (p<.001) was presumably due to inhibition of sickling due to CO retention. Examination of post mortem tissues showed localized obstructipn of microvessels by dense aggregates of sickled cells. The relatively low proportion of sickled cells in larger vessels was consistent with the small number of sickle cells in post mortem blood specimens. These studies indicate that selective local trapping of circulating sickled cells occurs in the rat model. In man, unlike the rat, this is followed by stasis and further sickling, making it impossible to distinguish between the originally trapped sickled cells and cells that subsequently sickled. These findings suggest that trapping of circulating sickled cells may initiate the vaso-occlusive crisis. (Supported by USPHS Grant HL-14808)

HYPONATREMIA IN SICKLE CRISIS — A DEFECT IN RENAL DILUTING CAPACITY

A ten year old patient with thalassemia major who had been maintained on a chronic hypertransfusion regimen for 8 years, presented with a tonic-clonic seizure. Admission laboratory data included a serum level of total calcium of 5.7 mg/dl, ionized calcium 2.08 mg/dl, inorganic phosphorus 7.8 mg/dl, and alkaline phosphatase 1.2 BLU. Although liver function was abnormal with elevated transaminases, serum 25 hydroxyvitamin D level was normal at 21.8 ng/ml. Concentration of immunoreactive parathyroid hormone was relatively decreased at 15 μlEq/ml. Skeletal radiographs were normal. Evaluation of other endocrine, renal and gastrointestinal functions, were normal. Urinary excretion of calcium and cAMP were 43 mg/24 hrs. and 2.75 nmol/mg creatinine/24 hrs. respectively, which are both markedly decreased from normal. All studies indicated hypoparathyroidism presumably due to iron deposition in the gland. 1,25-dihydroxycholecalciferol in an oral dose of 0.5-0.75 μg/d, in this 22 kg child, corrected the hypocalcemia within 7 days of initiating treatment. Serum ionized calcium level has remained normal for 100 treatment days with no evidence of hypercalcemia or hypercalcuria on a dose of 1.0-1.5 μg/d of the hormone.Four other children maintained on chronic hypertransfusion for thalassemia major had no evidence of hypocalcemia. This form of hypoparathyroidism is recorded to alert the clinician to a significant complication and effective new treatment plan in thalassemia major.

Isoimmune Neonatal Neutropenia Due to a New Neutrophile-specific Antibody

Patients with sickle cell disease have a well known defect in renal concentrating ability. When in crisis these patients are usually treated with large volumesof intravenous and/or oral fluids. This study was prompted by the observation of several children in sickle crisis who developed severe hyponatremia with C N S symptoms while having high concentrations of sodium in the urine.Patients with mild to moderate pain and/or infection were studied. On admission to the hospital 10/51 patients had sodium concentrations in serum below 135<mEq/1. The mean osmolality of serum of 28 patients was 278mOsm/1, with 7/28 below 271mOsm/1. The urine osmolality was greater than the serum osmolality in 19/20, with a mean urine osmolality of 436mOsm/1 and a range of 265 to 673mOsm/1. The ratio of sodium concentration in the urine to that in the plasma(U/P) was greater than 0.95 in 10/31 patients with a mean of 0.73. Creatinine clearances were normal or increased free water excretion was reduced, and Na clearances were usually very high despite hyponatremia. These results indicate that the renal defect in sickle cell disease is not hyposthenuria, but rather a narrow range of solute concentration, with limited diluting as well as concentrating capacity. These patients have a tendency to lose excessive amounts of electrolyte in the urine,particularly during crisis, and are unable to handle a water load at these times. These findings have significant implications for supportive therapy.