Maria Varvoutsi

Vincristine Overdose: Experience with 3 Patients

Vincristine overdose (7.5 mg/m2) was accidentally administered to 3 children with acute lymphoblastic leukemia. Treatment included double-volume exchange transfusion, phenobarbital administered prophylactically, and folinic acid rescue 18 mg every 3 hours for 16 doses. Vincristine levels were also assayed and showed a dramatic decline in postexchange levels in the 2 patients who survived and an almost unchanged value in the patient who succumbed. Early signs of toxicity in the 2 survivors were peripheral neuropathy (day 4), bone marrow toxicity (day 5), gastrointestinal toxicity (days 6 and 7), and hypertension (days 7 and 8). Marrow aplasia lasted for 4 and 10 days, peripheral neuropathy for 15 and 42 days, gastrointestinal toxicity for 3 and 5 days, and hypertension for 5 and 14 days. The 2 children were discharged on days 13 and 16 and cytostatic therapy was restarted on days 18 and 25. Both are alive without evidence of leukemia. The third patient developed liver and marrow toxicity on day 3 and died on day 9. Postmortem examination showed leukemia infiltration of the liver and spleen.

Longitudinal assessment of immunological status and rate of immune recovery following treatment in children with ALL

We prospectively evaluated the immunological status, immune recovery and risk of infection in pediatric ALL patients treated on the BFM 95 protocol.

Differences Between Younger and Older Patients with Childhood Hodgkin Lymphoma

From 1979 to 2006, 74 children with Hodgkins lymphoma were treated at our center. Among them, 15 (14 boys and 1 girl) and 59 (33 boys and 26 girls) patients were younger and older than 8 years, respectively. Six (40%) children among younger patients and 26 (44%) among older patients had advanced stage disease. We detected 3 (20%) relapses among younger patients and 5 (8.5%) among the older patients. All of younger patients are alive whereas three of the older patients have died. Second malignancy developed in one and three children among younger and older patients, respectively. The only difference that was detected concerning the age was a male predominance among the younger patients.

Optic pathway glioma in children: 10 years of experience in a single institution

ABSTRACT Optic pathway glioma (OPG) is a rare brain tumor that occurs more commonly during early childhood and is frequently associated with neurofibromatosis type 1 (NF1). In this study, our aim was to describe the characteristics, management, and outcome of patients with OPG. We retrospectively analyzed the clinical charts of all children diagnosed with OPG at our institution from 2003 to 2013. Twenty children (11 boys and 9 girls, median age: 5 and 3/12 years; NF1: 15/20) were diagnosed with OPG. The diagnosis was based on magnetic resonance imaging (MRI) findings. A biopsy was useful in 3 patients. The main reason for seeking medical advice was decreased vision (7/20 patients), whereas in 10/20 patients, the diagnosis was established during the routine follow-up for their NF1. Fifteen patients demonstrated MRI findings of optic nerve involvement and/or chiasmal tumor, whereas in 5 children, postchiasmal structures were also involved. Sixteen patients (16/20) received carboplatin-based regimens, whereas 4/20 patients were only under close observation. Six patients showed deterioration of visual acuity and/or imaging findings at the end of treatment and/or during their follow-up. Three of them (3/6) underwent tumor resection, whereas 1 (1/6) received radiation treatment. None of our patients had total blindness from both eyes. Half of our patients were diagnosed during follow-up for their NF1, the incidence of which was high in our group. Our data suggest that chemotherapy helps in the preservation of vision in the majority of children.

Malignant Peripheral Nerve Sheath Tumors in Children with Neurofibromatosis Type 1

Purpose. Malignant peripheral nerve sheath tumors (MPNSTs) are rare in children and account for approximately 5–10% of all soft tissue sarcomas in adults. MPNSTs may occur independently but individuals with neurofibromatosis type 1 (NF1) have a significantly increased risk. Our aim is to present patients with MPNST treated in our department. Cases and Results. In this report we present 4 cases of MPNSTs (3 females: 13, 12, and 13 years old and 1 male: 10 years old) arising in patients with NF1. All of them presented with an enlarging mass and pain at diagnosis. Tumor was located in the buttock, the spinal cord, the trunk, and the left leg proximal to the heel. Wide excision of the tumor and radiotherapy were applied to all and adjuvant chemotherapy was given to three of them after the disease was progressed. All four died 32, 18, 10, and 22 months after diagnosis with progressive disease locally and pulmonary metastases in two of them. Conclusions. In conclusion, MPNSTs arising in patients with NF1 are high grade sarcomas with short survival. Individuals with NF1 should be followed closely in order to identify early the development of MPNSTs. Aggressive surgery and complete excision significantly improves disease-free survival. The usefulness of radiation therapy in MPNSTs is not determined although all patients will receive radiation therapy at some stage of the disease. The role of chemotherapy is unclear.

A Novel Karyotype in Acute Myeloid Leukemia with Basophilia

Acute basophilic leukemia is a distinct entity of Acute Myeloid Leukemia (AML) with primary differentiation to basophils. Increased basophil count has been described in AML cases with translocation t(6;9)(p23;q34) or other chromosomal abnormalities. We describe a 15-year old female teenager with AML and excess peripheral blood and bone marrow basophils. Her white blood cell count at diagnosis was 15.4 G/L with 53% basophils and 17% blasts. The bone marrow cytogenetics analysis did not reveal any of the usual abnormalities. The karyotype showed two closely related leukemic clones: the first (16 metaphases), with a total of 48 chromosomes, had an extra chromosome 8 with deletion of the long arm and an additional 21 (48,XX, +del(8)(q24.2q24.3), t21[16]), while the second clone (2 metaphases), with a total of 47 chromosomes, did not contain the extra 21 chromosome (47, sl, −21[2]). In summary, in this case of AML-M2 with excess basophils, there is a novel chromosomal abnormality, not previously reported in this entity.

Successful treatment in a child with anaplastic large cell lymphoma and coexistence of pulmonary tuberculosis.

A 13-year-old girl was admitted to our department with a history of severe pain of her left axilla and fever. On physical examination, a block of lymph nodes in her left axilla, diffuse papular rash, and red-violet swelling of her supraclavicular and subclavian region were noted. Imaging investigations revealed left axillar and supraclavicular lymphadenopathy and a small nodular shade in the upper lobe of her left lung. A biopsy from an axillary lymph node established the diagnosis of anaplastic large cell lymphoma (ALCL), whereas DNA of Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR) in the same tissue biopsy. Patient was started on chemotherapy for ALCL and achieved remission of all initially involved fields. Nevertheless, two new nodular lesions were detected in the left lower lobe. Biopsy revealed granulomas, and PCR was positive for M. tuberculosis. Our patient received treatment with the combination of isoniazid and rifampin (12 months), pyrazinamide (the first 2 months), and maintenance chemotherapy for her ALCL for one year simultaneously. Four years later, she is disease free for both mycobacterial infection and lymphoma. We are reporting this successful management of mycobacterial infection in a patient with ALCL despite intensive chemotherapy that the patient received at the same time.

SUCCESSFUL COMBINATION OF ANTIFUNGAL AGENTS AND SURGICAL RESECTION FOR PULMONARY ASPERGILLOSIS IN A CHILD WITH HODGKIN DISEASE: Review of the Literature

The authors report on a 14-year-old adolescent boy suffering of Hodgkin disease in remission, who developed autoimmune anemia and thrombopenia. He was treated with high-dose steroids and he developed serious invasive lung aspergillosis, which was treated with antifungal agents and surgical intervention. Children suffering from cancer are prone to develop systemic fungal infections secondary to the severe immunosuppression caused by the disease itself and the antineoplastic therapy. Intravenous antifungal medications and, when feasible, surgery are used for treatment of pulmonary aspergillosis. Factors related to better outcome are early diagnosis, remission of underlying disease, aggressive antifungal therapy, and recovery from neutropenia.

Pediatric B-cell Non-Hodgkin Lymphoma: 21-year Experience with FAB-LMB Protocols in a Single Institute in Greece

Aims and background: Our objective was to analyze the clinical and demographic characteristics of children with B-cell lymphoma treated in a single center over the last two decades. Methods: Data was collected by a retrospective review of the charts of all 76 patients treated to our unit, from 1990 to 2010, with FAB LMB 89, 96 protocols and 2003 modifications. Results: The median age was 8.03 years, with a male predominance 3.7:1. According to LMB staging criteria, 7 patients (9.2%) were classified as Group A, 53 (69.7%) as B and 16 (21.1%) as C all but 1 with bone marrow involvement and in 8 combined with CNS involvement. Most of our patients (46/76 - 60.5%) had abdominal tumours. Eight children of A and B Group (8/60, 13.3%) were upgraded to Group C due to poor treatment response. Regarding outcome, 11 patients died, 8 due to disease, 3 due to toxicity, 2 in induction and 1 post autograft. Relapse occurred in 10 children (13.2%), all with abdominal disease, one of them with concurrent mediastinal involvement. Most relapsed patients (7/10) were initially treated as Group B (7/53, 13.2%), 2 as C and 1 as Group A. The outcome of relapsed children was dismal, as 6/10 (60%) died. Conclusions: In our results, the survival rate is generally excellent (65/76, 85.53 %) more than one year off treatment, which generally means cure in B-cell lymphomas. Children with unsatisfactory response to treatment and recurrent disease have a dismal prognosis.

Successful Treatment in Children with Hodgkin Lymphoma in Greece; A 20-Year Experience in a Single Institution

During the last 30 years, combined chemotherapy regimens with radiotherapy or not significantly improved the prognosis for patients with Hodgkin lymphoma. We retrospectively studied 58 children (35 boys and 23 girls) with Hodgkin lymphoma who were treated at our institution during the period 1987–2006 and we correlated age, sex, stage, histology, and therapy with the outcome of patients. Of our patients, 9 children were 8 years old or younger. Nodular sclerosis was the predominant histology subtype (69%), whereas 26 patients (45%) had advanced disease (stage III or IV). Chemotherapy (CT) with various drug combinations, according to the period of treatment plus low-dose involved field radiation therapy (IFRT), was used in all patients. Five children experienced relapse and in 3 other patients second or third malignancies were documented. The overall survival was found to be 98%. No factors related to the outcome could be detected. The prognosis of children with Hodgkin lymphoma is excellent with CT combined with low dose IFRT but in long-time survivors late effects of the combined modality treatment are still issues of major concern. Longer followup of a greater number of patients is necessary to detect prognostic factors related to the outcome of children with Hodgkin lymphoma and to identify some patients who would be treated without radiation.