Neuroblastoma.

OBJECTIVE: Due to the poor results achieved on combination chemotherapy and the unproven cost-effectiveness value of myeloablative therapy, the question has been raised; should patients with stage IV neuroblastoma be actively treated? The aim of the current study is to analyze retrospectively treatment results of 43 children with neuroblastoma with special stress on the rate and duration of remission in children with disseminated neuroblastoma. METHODS: Treatment of children with neuroblastoma consisted of surgical removal of the tumor, if possible, followed by chemotherapy for unresectable residual tumor including metastases. Second look surgery was performed to resect residual masses rendered resectable on chemotherapy in the absence of distal metastases. The chemotherapy protocol used in the current study consisted of alternating combination chemotherapy regimens containing, Cyclophosphamide, Vincristine and Doxorubicin, alternating with Cis-platinum and Etoposide. RESULTS: The male to female ratio was 2:1 with a median age of 2.1 years. The abdomen was the primary site of involvement encountered in 32 patients (74%). According to the childrens cancer study group (CCSG) staging system, only 6 patients (14%) had localized tumors (stages I and II). Two patients (5%) were found to have stage IV. Stage III was documented in 5 patients (12%). The majority of patients (70%) had disseminated disease at presentation. The bone marrow was the most common site of metastatic deposit, encountered in 23 patients out of the 30 with stage IV disease (77%). Out of the 12 evaluable non-stage IV patients, only one patient (8%) showed treatment failure. Assessment of response by the end of the 6th month from the date of diagnosis revealed that out of the 27 evaluable patients with stage IV, 4 patients achieved complete remission, 7 patients achieved very good partial remission, 8 patients achieved partial remission and 4 patients achieved mixed response. Three patients showed progressive disease on chemotherapy. Twenty-one patients (78%) were symptom-free and were conducting normal life. Assessment of response to treatment by the end of the 12th month from diagnosis revealed that 6 patients (2 complete remissions, 1 very good partial response, 3 partial responses) were maintaining their remission. Out of the 19 patients showing complete or partial remission at early assessment, 4 patients maintained their remission for more than 18 months. Two (one was in complete remission and the other was in partial response) of them progressed in areas of previous involvement after 20 and 21 months. The other 2 patients (one was in complete remission and the other was in partial response) showed disease progression in areas not previously affected by disease at presentation after 23 and 42 months. CONCLUSION: Results of treatment by multiagent chemotherapy regimens used in the current study show that children with neuroblastoma, even those with advanced stages, should receive the benefit of intensive multimodal therapy, even those with partial response to initial therapy. These patients may experience reasonable symptom-free and sometimes, disease-free survival.

Differentiated thyroid carcinoma referred for radioiodine therapy.

OBJECTIVE: The current work was conducted to study the disease status and treatment results of patients with differentiated thyroid carcinoma referred for radioactive iodine therapy. METHODS: Retrospective review of 78 patients with differentiated thyroid carcinoma referred for radioiodine therapy in the Nuclear Medicine Unit, King Abdulaziz Hospital and Oncology Center, Jeddah, Kingdom of Saudi Arabia. Analysis of the clinicopathologic characteristics, age correlation to different risk factors, treatment protocol and results were performed. RESULTS: Seventy seven percent were female and the female to male ratio was 3.5:1. The age of patients ranged between 13-63 years with a median age of 36 years. Cervical lymph node involvement was detected in 22 patients (25%). Papillary carcinoma was encountered in 78 patients (90%) and follicular carcinoma in 9 patients (10%). Analysis of the clinicopathologic characteristics showed no statistically significant difference between patients in the different age groups except for extrathyroid extension and lymph node involvement. Patients older than 45 years had a statistically significant lower incidence of nodal involvement and higher incidence of extra thyroid extension (P<0.02). In the current study we used a high dose method (Radioiodine-131 dose 75-100mCi) for thyroid remnant ablation after thyroidectomy (total or near total) in 67 patients. An Iodine 131 dose of 150 mCi was used in 12 patients with radioiodine-avid cervical lymph nodes and in 3 patients with gross residual tumor. In 4 patients with distant metastases an Iodine 131 dose of 200 mCi was used. For the whole study group the 5 year overall survival and disease-free survival was 96% and 88%. CONCLUSION: The current study, as with many other retrospective studies, concluded that despite the fact that differentiated thyroid carcinoma is among the most curable cancers, some patients are still at high risk for recurrent disease and associated mortality.

Fever and granulocytopenia in children with acute lymphoblastic leukemia under induction therapy.

OBJECTIVE: Infection is one of the most serious complications of cancer therapy. The rationale of using broad spectrum antibiotics prophylactically has led to a great change in the causative organisms. The aim of the present study is to review retrospectively the type and sequence of infectious complications among Saudi children with acute lymphoblastic leukemia. METHODS: A total of 233 febrile episodes were observed in 137 children with acute lymphoblastic leukemia under induction therapy using modified BFM protocol were studied. RESULTS: Profound neutropenia (Absolute Neutrophil count < 100/mm3) was encountered in 72 episodes (31%). Clinical signs and symptoms suggestive of infection were evident in 39% of the neutropenic episodes. The respiratory system was the most frequently affected site encountered in 17% of the episodes. Microbiologically documented infection was recorded in 59% (n=137) of the fever and granulocytopenia episodes. In 96 episodes (41%), there was neither clinical nor microbiological evidence of infection fever of unknown origin. Out of the 932 cultures, positive isolates were detected in 346 cultures (37%). Gram positive cocci were the most frequently organisms (54%) followed by gram negative bacilli (39%). In the current study, 7 patients (3%) died because of direct or indirect consequences of infection. CONCLUSION: The current study stresses the importance of frequent reviewing of the type, frequency, severity and outcome of infection complications over years to detect changing epidemiological patterns.

Neuroblastoma: A clinical review.

OBJECTIVE: Due to the poor results achieved on combination chemotherapy and the unproven cost-effectiveness value of myeloablative therapy, the question has been raised; should patients with stage IV neuroblastoma be actively treated? The aim of the current study is to analyze retrospectively treatment results of 43 children with neuroblastoma with special stress on the rate and duration of remission in children with disseminated neuroblastoma. METHODS: Treatment of children with neuroblastoma consisted of surgical removal of the tumor, if possible, followed by chemotherapy for unresectable residual tumor including metastases. Second look surgery was performed to resect residual masses rendered resectable on chemotherapy in the absence of distal metastases. The chemotherapy protocol used in the current study consisted of alternating combination chemotherapy regimens containing, Cyclophosphamide, Vincristine and Doxorubicin, alternating with Cis-platinum and Etoposide. RESULTS: The male to female ratio was 2:1 with a median age of 2.1 years. The abdomen was the primary site of involvement encountered in 32 patients (74%). According to the childrens cancer study group (CCSG) staging system, only 6 patients (14%) had localized tumors (stages I and II). Two patients (5%) were found to have stage IV. Stage III was documented in 5 patients (12%). The majority of patients (70%) had disseminated disease at presentation. The bone marrow was the most common site of metastatic deposit, encountered in 23 patients out of the 30 with stage IV disease (77%). Out of the 12 evaluable non-stage IV patients, only one patient (8%) showed treatment failure. Assessment of response by the end of the 6th month from the date of diagnosis revealed that out of the 27 evaluable patients with stage IV, 4 patients achieved complete remission, 7 patients achieved very good partial remission, 8 patients achieved partial remission and 4 patients achieved mixed response. Three patients showed progressive disease on chemotherapy. Twenty-one patients (78%) were symptom-free and were conducting normal life. Assessment of response to treatment by the end of the 12th month from diagnosis revealed that 6 patients (2 complete remissions, 1 very good partial response, 3 partial responses) were maintaining their remission. Out of the 19 patients showing complete or partial remission at early assessment, 4 patients maintained their remission for more than 18 months. Two (one was in complete remission and the other was in partial response) of them progressed in areas of previous involvement after 20 and 21 months. The other 2 patients (one was in complete remission and the other was in partial response) showed disease progression in areas not previously affected by disease at presentation after 23 and 42 months. CONCLUSION: Results of treatment by multiagent chemotherapy regimens used in the current study show that children with neuroblastoma, even those with advanced stages, should receive the benefit of intensive multimodal therapy, even those with partial response to initial therapy. These patients may experience reasonable symptom-free and sometimes, disease-free survival.

HELLP syndrome: Clinical profile of seven patients.

HELLP syndrome is a multi-organ disorder unique to pregnancy. It is characterized by hemolysis, elevated liver enzymes, and low platelets in patients with pre-eclampsia or eclampsia. In King Abdulaziz Oncology Center, Jeddah, seven patients with HELLP syndrome were admitted over a period of four years (1991-94). Retrospective analysis of data was done to study the clinical profile of HELLP syndrome. The incidence of HELLP syndrome in our institution was 1 per 2285 deliveries. One patient was Saudi and six were non-Saudis. The age range was 23 to 44 years, with a mean of 29 years. All patients were multipara. The disorder occurred between 24 to 33 weeks of gestational age, the average being 29 weeks. The most commonly encountered clinical feature was right upper quadrant/epigastric pain. Other features included nausea/vomiting, jaundice, hepatic encephalopathy, azotemia, hypotension and grand mal convulsions. All patients had severe pre-eclampsia pr eclampsia. Indirect hyperbilirubinemia was in the range of 2 to 8 mg/dL and elevated transaminases up to 229 U/L (n<40 U/L) were noted. Various degrees of peripheral thrombocytopenia (<150x10(9)/L) were present in seven patients. Four patients had elevated prothrombin and partial thromboplastin time with postive fibrinogen degradation products. Laboratory abnormalities returned to normal within 10 days following delivery. Four patients were delivered by cesarean section and three had vaginal deliveries. We had two maternal deaths (mortality 34%). One died of multi-organ failure and the other with adult respiratory distress syndrome. There was one stillbirth and the second baby died soon after birth due to prematurity (infant perinatal mortality 34%). We conclude that HELLP syndrome is rare among pregnant women in our institution. It should always be suspected in women with pre-eclampsia or eclampsia when they present with upper abdominal pain. Multipara seem to be more afflicted. Subclinical disseminated intravascular coagulation was detected in 55% of the patients. A majority of our patients presented late to the hospital.

Splenic irradiation as primary therapy for prolymphocytic leukemia.

A patient with prolymphocytic leukemia (PLL), a lymphoproliferative disorder that carries a poor prognosis, is presented. The disease was diagnosed at an early stage and treatment could be delayed for four years. When massive, painful splenomegaly developed, splenic irradiation (SI) was chosen as the primary form of therapy and an excellent systemic response could be achieved. Our observation is in agreement with preliminary studies, which advocate SI as the primary form of therapy in PLL. Furthermore, it is emphasized that an early diagnosis of PLL is necessary to establish its true course and that the prognosis may be better than originally thought.