Multiple intracranial tumors in Philadelphia chromosome positive acute lymphoblastic leukemia: successful treatment following aggressive supportive care, early cranial radiation, high dose chemotherapy and imatinib

We report the first case of multiple intracranial tumors ("chloromas") at diagnosis of Philadelphia chromosome positive acute lymphoblastic leukemia. The patient presented comatose with signs of cerebral herniation. Initial management of raised intracranial pressure and hyperleukocytosis followed by emergent whole brain radiation therapy reversed the life-threatening neurological signs. High-dose chemotherapy combined with daily imatinib mesylate induced a rapid and sustained bone marrow remission. Ongoing rehabilitation resulted in a near complete neurological recovery within 6 months of diagnosis. This outcome justifies aggressive early management of increased intracranial pressure and hyperleukocytosis in future similar presentations.     

Conservative management of priapism secondary to leukemia

We report four cases of leukemia (three chronic myeloid and one T-cell acute lymphoblastic) presenting with priapism in children 9- to 13-year old. All of them presented with hyperleukocytosis, and three had anemia plus thrombocytosis. All patients underwent chemotherapy and two had leukopheresis. In all cases, priapism was managed conservatively. Erection required up to 13 days to start improving but none of the patients developed clinical evidence of long-term erectile dysfunction. Based on these cases, conservative management of priapism in children with leukemia might be adequate and not lead to long-term erectile dysfunction.     

High-flow priapism in acute lymphatic leukaemia

Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation. It is associated with excessive hyperleukocytosis (e.g. in acute or chronic leukaemia); however, this complication is rarely seen in the pediatric population. We report a 12-year-old boy suffering from acute leukaemia presenting with, at first intermittent, but increasingly persistent erection. Doppler US revealed signs of high-flow priapism. MRI excluded intrapelvic tumour masses, and three-dimensional contrast-enhanced MR angiography could not demonstrate an arteriovenous fistula or thrombosis. Cavernosal blood-gas measurement was in agreement with high-flow priapism. On the basis of the imaging findings, invasive therapeutic management was avoided in our patient with a successful outcome.     

"Pseudoleukemia" in a newborn infant with trisomy 21]

The increased incidence of leukemia in patients with trisomy 21 is well established. A blood disorder which may be mistaken for acute leukemia may occur in infants with trisomy 21. The authors report a newborn with trisomy 21 and hematologic findings suggesting acute leukemia (hyperleukocytosis, anemia, thrombocytopenia; replacement of bone marrow by blast-like cells). Without treatment spontaneous and complete recovery occurred. Cytochemistry and therapy are discussed in this paper.     

Atypical presentation of acute myeloblastic leukemia in two pediatric patients

Acute myeloblastic leukemia (MLA) is an uncommon disease in childhood and its prognosis is worse than that of lymphoblastic leukemia. Severe hemorrhage, infections and perfusion disorders secondary to leukostasis are the main complications leading to its high mortality rate. Two pediatric patients with MLA (M5a and M2) are presented. Both patients were admitted to the pediatric intensive care unit with acute respiratory distress syndrome and intracranial hemorrhage respectively, secondary to leukostasis. The first patient showed favorable clinical course and underwent bone marrow transplantation four months later; in contrast, the second patient died a few hours after admission. The physiopathology of each case, the therapeutic approach and the use of leukopheresis as a therapeutic alternative in patients with hyperleukocytosis and leukostasis are discussed. A high degree of suspicion is required to make a diagnosis as early as possible in order to avoid the death of a large percentage of patients before cytostatic treatment begins.     

SUCCESSFUL USE OF TERBUTALINE IN PERSISTENT PRIAPISM IN A 12-YEAR-OLD BOY WITH CHRONIC MYELOID LEUKEMIA

A 12-year-old boy had been suffering from intermittent episodes of penile erection for 2 weeks. For the last 2 days, however, the patient had been having sustained priapism and had to be admitted in a private hospital for management. Investigations revealed high total leukocyte counts. He was referred to the authors’ hospital where a diagnosis of chronic myeloid leukemia was made. He was started on intravenous hydration, hydroxyurea, and allopurinol. Imatinib was added 2 days later. The parents refused surgical intervention. Despite a reduction in the counts the priapism persisted and the pain was unresponsive to opioids. Administration of terbutaline was associated with a successful outcome resulting in relief from pain within 20 min. The priapism also resolved completely in 1 day.     

Supportive care for children with cancer. Guidelines of the Childrens Cancer Study Group. Managing the problem of hyperleukocytosis in acute leukemia

The presence of very high numbers of circulating leukemic blast cells is reported to be associated with an increased risk of fatal complications secondary to hyperviscosity of blood and leukostasis, tumor lysis causing metabolic derangements, intravascular coagulopathy, and proliferation of leukemic cells in the brain leading to intracranial hemorrhage. Transfusions of red cells further increases the possibility of fatal leukostasis. Recommendations for care of these patients include adequate hydration, alkalinization, control of uric acid production with allopurinol, correction of the many possible fluid and electrolyte problems, possible use of hemodialysis, avoidance of excessive transfusions, and the careful use of antileukemic drugs at the outset of therapy. Cranial radiation, leukapheresis, and exchange transfusions have been used in the hope of preventing the sometimes fatal complications in leukemic patients with hyperleukocytosis. However, the effectiveness of these techniques remains in question.     

Infant leukemia in Japan: clinical and biological analysis of 48 cases

Forty-eight Japanese infants with acute lymphoid leukemia (ALL) (n = 24) and acute nonlymphoid leukemia (ANLL) (n = 24) were analyzed on the basis of clinical and laboratory data. Morphologically, 20 of the 24 infants with ALL were of the FAB L1 type, and 20 of the 24 infants with ANLL were of the M4 or M5 type. Markedly enlarged liver and spleen, and hyperleukocytosis (more than 50,000/microliters) were seen in 9, 12, and 14 infants with ALL and 10, 11, and 10 infants with ANLL, respectively. Initial CNS leukemia was evident in 2 infants. Chromosome studies of the leukemic cells showed abnormal karyotypes in 9 of the 21 infants with ALL and 19 of the 22 infants with ANLL, consisting mainly of translocation 11, 12, and inversion 16. By surface marker analysis, only 7 of the 22 infants with ALL (32%) were diagnosed as having common ALL (HLA-DR+, CD19+, CD10+). Of the 15 infants with ANLL, 12 and 5 infants also showed reactivity to HLA-DR and CD19, respectively. All of the 5 ANLL infants with lymphoid markers showed different leukemic cell features at the time of relapse. Twelve of the 19 infants with ALL (63%) who achieved a complete remission relapsed within the first 2 years; 8 of the 21 with ANLL (38%) relapsed within the first year. Analysis of event-free survival shows that the ALL infants with hyperleukocytosis have a poorer prognosis than those without hyperleukocytosis (p less than 0.05). Infant leukemia originates in a multipotent cell with lymphoid and myeloid features, and intensive multiagent chemotherapy is necessary for the treatment of infants with acute leukemia.     

Relapse of precursor B-cell acute lymphoblastic leukemia as an isolated central nervous system mass lesion 9 years after initial diagnosis

Seven years after completion of chemotherapy for acute lymphoblastic leukemia, diagnosed at the age of 5 years, a black female presented with signs of increased intracranial pressure. Neuroimaging showed a large enhancing extra-axial occipital tumor mass. The resection specimen showed morphologic, cytogenetic, and immunophenotypic features consistent with relapse of the primary leukemia. Bone marrow examination was negative for malignancy. The long duration of complete remission followed by the formation of a mass in the central nervous system are highly unusual features of recurrent acute lymphoblastic leukemia. © 1996 Wiley-Liss, Inc.     

Tumefactive intracranial presentation of precursor B-cell acute lymphoblastic leukemia

In children, leukemia is the most common malignancy, and approximately 75% of leukemias are acute lymphoblastic leukemia (ALL). Central nervous system leukemia is found at diagnosis in fewer than 5% of children with ALL. Leukemic intracranial masses have been described with acute myeloid leukemia, but ALL presenting as a mass lesion is rare. We describe a unique case of an intracranial confirmed precursor B cell (pre-B) ALL mass in a 13-year-old girl that was diagnosed by brain CT, MRI and cerebral angiography, and confirmed by biopsy. This report details pertinent history and distinguishing imaging features of an intracranial ALL tumefaction.     

ADad 3: The Epidemiology of Anxiety Disorders Among Adolescents in a Rural Community Population in India

Hyperleukocytosis is defined as peripheral blood leukocyte count exceeding 100,000/mm³. Acute leukemia is the most common etiology in pediatric practice. Hyperleukocytosis is a medical emergency. The increased blood viscosity, secondary to high white cell count and leukocyte aggregates, results in stasis in the smaller blood vessels. This predisposes to neurological, pulmonary or gastrointestinal complications. In addition, patients are at risk for tumor lysis syndrome due to the increased tumor burden. Initial management includes aggressive hydration, prevention of tumor lysis syndrome, and correction of metabolic abnormalities. A red cell transfusion is not indicated in a hemodynamically stable child, as it adversely affects the blood viscosity. Leukapheresis is the treatment of choice for a very high count, or in patients with symptomatic hyperleukocytosis. The technical expertise required, a relative difficult venous access in younger children, risk of anticoagulation and possible non-availability of the procedure in emergency hours are limitations of leukapheresis. However, it is a rewarding procedure and performed with relative ease in centers that perform the procedure frequently. An exchange transfusion is often a practical option when hyperleukocytosis is complicated with severe anemia. The partial exchange aids in correcting both, without the risk of volume overload or hyperviscosity, which are the limitations of hydration and blood transfusion, respectively. Etiology and management of hyperleukocytosis in relevance to the pediatric emergency room is outlined.     

Priapism in pediatrics: initial presentation of chronic myeloid leukemia

Priapism is a prolonged penis erection, triggered by sexual stimulation or not; it is uncommon in children, but its knowledge is of great importance since it may lead to suspect serious diseases, such as leukemia, and it can lead to permanent erectile dysfunction if appropriate treatment is not timely done. We present the case of a 16-year-old boy with priapism which lead to a diagnosis of chronic myeloid leukemia. Knowledge of an uncommon pathology in children, like priapism, it is very important in order to establish the suitable and timely treatment, to prevent the irreversible sequelaes and complications of this disease.     

Priapizm – niezwykle rzadki pierwszy objaw ostrej białaczki limfoblastycznej

Priapism or prolonged erection of the penis is extremely rare in pediatric population, and occurs mostly in hemoglobinopathies, hypercoagulable states, in cancer and spinal injuries. There are two types of priapism: high and low blood flow, and their differentiation is based on the clinical picture and the study of blood gas analysis of blood aspirated from the corpus cavernosum. Ischemic priapism is a condition requiring urgent intervention and currently the gold standard adopts the aspiration of the corpora cavernosa rinsing with saline and drug administration – (sympathomimetics and alpha-adrenergic agonists). In this paper we present a case of priapism in a 9-year-old boy with acute lymphoblastic leukemia (ALL).     

Leukoreduction in patients with severe pertussis with hyperleukocytosis

When pertussis is associated with hyperleukocytosis, mortality approaches to 80%. Immature leukocytes have been identified in pulmonary arterioles, small arteries and venules. Techniques aimed at reducing leukocyte mass might improve the prognosis of these patients. We report our experience with 3 patients in whom a leukoreduction was performed in the context of severe pertussis and hyperleukocytosis.     

Acute lymphoblastic leukemia with hyperleukocytosis, sinus pauses, and hypoxemic respiratory failure in an infant

A 5-month-old female infant presented with new-onset acute lymphoblastic leukemia and hyperleukocytosis with white blood cell count of 352 × 10(9) cells/L. She developed sinus pauses and hypoxemic respiratory failure. A manual single volume exchange blood transfusion was done with complete resolution of sinus pauses and hypoxemia.     

Transitorisch myeloproliferatives Syndrom bei Neugeborenen mit Down-Syndrom

Transient myeloproliferative syndrome (TMS) is a disorder of neonates with Down syndrome (trisomy 21) and occurs at an incidence of up to 10%. Typical for this entity is a proliferation of myeloid blasts with megakaryoblastic and/or erythroblastic features detectable in the peripheral blood. In the majority of cases TMS is asymptomatic, and only a small percentage of children show clinical symptoms due to hyperleukocytosis, thrombocytopenia, anemia, or hepatomegaly. Almost all children will achieve spontaneous remission after 2–4 months (disappearance of myeloid blasts and regression of clinical symptoms). Patients with initial hyperleukocytosis and hepatomegaly, however, carry a particular risk of developing hepatopathy followed frequently by lethal liver fibrosis. Chemotherapy with cytarabine is indicated in patients with clinical symptoms of hyperleukocytosis or early signs of hepatopathy. Within the first 4 years the risk of developing acute myeloblastic leukemia (AML) is high at 20–30%; therefore, regular follow-ups are advised. This analysis is based on one of the largest databases for TMS.     

Optic neuropathy in children with Lyme disease

Involvement of the optic nerve, either because of inflammation or increased intracranial pressure, is a rare manifestation of Lyme disease. Of the 4 children reported here with optic nerve abnormalities, 2 had decreased vision months after disease onset attributable to optic neuritis, and 1 had headache and diplopia early in the infection because of increased intracranial pressure associated with Lyme meningitis. In these 3 children, optic nerve involvement responded well to intravenous ceftriaxone therapy. The fourth child had headache and visual loss attributable to increased intracranial pressure and perhaps also to optic neuritis. Despite treatment with ceftriaxone and steroids, he had persistent increased intracranial pressure leading to permanent bilateral blindness. Clinicians should be aware that neuro-ophthalmologic involvement of Lyme disease may have significant consequences. If increased intracranial pressure persists despite antibiotic therapy, measures must be taken quickly to reduce the pressure.     

Spontaneous remission of congenital acute nonlymphoblastic leukemia with normal karyotype in twins

BACKGROUND: Congenital acute nonlymphoblastic leukemia (cANLL) is an extremely rare event and represents only 0.5-1% of the leukemias in the first year of life. It is usually more common among patients with chromosomal abnormalities. Transient myeloproliferative disease (TMD) is an hyperleukocytosis entity that occurs almost exclusively in Down syndrome patients and remits spontaneously. Spontaneous remission of congenital leukemia has been reported and related to the presence of an extra chromosome 21. PROCEDURE: A pair of non-Down syndrome newborn twins presented with a clinical picture of skin rash and hyperleukocytosis. Twin B had full-blown cANLL with bone marrow, peripheral blood, skin, CSF, and placental invasion. Twin A presented transient peripheral blood and skin involvement by the same type of blast cells. No cytotoxic therapy was given. With 2 years follow-up, they continue to do well. RESULTS: Histologic and immunophenotypical analysis of placentas, cord blood, skin, CSF, bone marrows, and peripheral blood revealed a consistent picture of intrautero cANLL in twin B, with transplacental invasion of twin A. Normal and blast cells were found to be karyotypically normal. Spontaneous remission occurred. CONCLUSIONS: cANLL with karyotypically normal blasts can develop a self-limited clinical course, which has resemblances to TMD.     

Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) refers to the constellation of deranged metabolic state, characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and/or azotemia, secondary to rapid breakdown of tumor cells. It is a life threatening emergency that typically follows administration of chemotherapy or may be spontaneous. Malignancies which have a large tumor burden, rapid turnover, as well as speedy breakdown following chemotherapy are susceptible. Acute lymphoblastic leukemia and non-Hodgkins lymphoma (particularly Burkitt’s lymphoma) are typically predisposed. TLS is best managed by early anticipation and preventive measures than the complicated task of treating an established TLS. Vigorous intravenous hydration is the cornerstone of prevention as well as treatment. Rasburicase has revolutionized the management. It is available in India for past 1 1/2 y, although the cost is a limiting factor. Children with acute leukemia in developing countries may reach health facility late, with severe anemia and hyperleukocytosis. Exchange transfusion may have to be restored to in such patients to simultaneously correct anemia and hyperleukocytosis and enable safe administration of fluids. Dialysis may be required when the metabolic ‘trash’ overwhelms the renal excretion, resulting in renal failure. Chemotherapeutic drugs are often administered in a phased manner in susceptible patients, in an attempt to prevent precipitous lysis of tumor cells. Presentation and management of TLS in relevance to the pediatric emergency room is outlined.     

Hyperleukocytosis from arsenic trioxide

We report the case of a 14-year-old male treated with arsenic trioxide for recurrent acute promyelocytic leukemia. He developed hyperleukocytosis (WBC 111.6 x 10(9)/L) which then resolved while continuing daily arsenic. Hyperleukocytosis without other complications may not be an indication for adding cytotoxic therapy or steroids, nor for discontinuing arsenic trioxide therapy in children.