Nkechi Onwuzurike

Venorelbine and methotrexate for the treatment of Rosai-Dorfman disease.

A 10-year-old African-American female developed right cervical lymph node enlargement about 2 months prior to a visit to our clinic onNovember 14, 1997. Shewas asymptomatic. She had several lymph nodes in the right side of the neck. The largest one measured 3 3 cm and was surgically removed. The histology showed sinus histiocytosis with massive lymphadenopathy (Rosai– Dorfman disease). The patient did well subsequently, but 4 years later in September of 2001 the lymphadenopathy recurred. At that time, she had progressively enlarging cervical lymph nodes, severe nasal obstruction with yellowish bloody nasal discharge of 8 months duration, and inability to breath well at night in the flat supine position.A computerized tomography (CT) showed pansinusitis, bilaterial partial blockage of osteomeatal complexes, and a posterior nasopharyngeal soft tissue mass. A posterior nasopharyngeal mass including the adenoid glandwas excised. The histology showedRosai–Dorfman disease. The difficulty in breathing and nasal obstruction resolved, but the enlarged cervical nodes persisted. Fivemonths later onMarch 4, 2002, she again developed difficulty in breathing and excessive fatigue that started 2–3 days prior to the visit. Multiple lymph nodes in the right neck were again noted. The enlarged lymph nodes collectively measured 16 11 cm. She was placed on prednisone 40 mg/m/day, and the symptoms rapidly subsided. The total area of the cervical swelling decreased to 12 8 cm in 4 days. Three weeks later, the dose was reduced to 25mg/m/day andwas continued at that dose for the next 2months, but no further reduction in the size of the mass occurred, and thick purulent nasal discharge continued. Because of this, 6-mercaptopurine (6MP) at 50 mg/m/ day by mouth (po) andmethotrxate (MTX) at 12mg/m po once a week as published by Horneff et al. [2] were started and continued for the next 2 months. There was no improvement. In fact lymph nodes increased in size. Prednisone was resumed at the dose of 40 mg/m/day The neck mass was partially surgically resected again on July 25, 2002, and prednisone was stopped. However, the nodes regrewwithin 6weeks and prednisonewas resumed, but this time no significant improvement occurred. In January 2003, she developed additional lymph node enlargement for the first time in the left neck. At this point, we started her on a combination of venorelbine 20 mg/m once a week, and methotrexate 30 mg/m IVonce a week in January 2003 according to the treatment protocol for fibromatosis [3]. Within 4 weeks, a clear reduction in the size of the lymph nodes was observed. A CT evaluation after 4 months of treatment showed a significant reduction in the size of the largest mass from 6.6 4.5 to 3.1 2.7 cm. Venorelbine and methotrexate were stopped after 24 weeks, though there were still residual enlarged nodes. Within the next month, therewas a rebound increase in the neck mass, and thus these two drugs were resumed on October 6, 2003 and continued for 9 more weeks. Again the lymph nodes decreased in size with the largest one being 1 1 cm. The patient has been off all medications for the last 12 months, and doing well. The natural history of SHML is that of spontaneous remissions and recurrences. Although, there have been some fatal cases [4], the disorder is regarded as a benign disease with eventual resolution in an overwhelming majority of cases. Thus the indications for interventions have been to manage symptoms, to remove compression of vital organs, or to correct severe disfigurement. In our case, an involvement of the retropharyngeal nodes and adenoids resulting in respiratory difficulty and sinusitis necessitated some formof treatment. The surgical removal gave the patient only temporary relief resulting in the subsequent steroid administration. Because of the side effects of long-term steroid administration and relative resistance to prednisone, we tried the combination of mercaptopurine and methotrexate, but this was totally ineffective. Other agents published to be effective are vincristine, or vinblastine and steroids [5,6]. In our clinic at that time, we were using a combination of venorelbine and methotrexate for a patient with desmoid tumor [2]. Venorelbine is pharmacologically very similar to vincristine and vinblastine, with much less neurotoxicity [2]. We were impressed by the lack of side effects.

Multiple fractures due to osteogenesis imperfecta mistaken as child abuse

A 15-month-old African–American boy receiving chemotherapy for Wilms tumour was diagnosed to have a fracture of left femur at the emergency department (ED) of our hospital. A month earlier, the patient had been seen at the same ED for a fracture of right femur. The skeletal survey this time also showed an old posterior rib fracture. Child abuse was suspected. The child’s custody was transferred to the maternal grandparents. However, 2 months later while with the grandparents, he sustained a fracture of the left distal tibia. This led to an investigation for osteogenesis imperfecta (OI). The child was found to have a collagen mutation, COL1A1, strongly suggesting that the child’s multiple fractures were most likely due to OI. The child had no physical stigmata of classical OI except for blue sclera. Multiple bone fractures alone without other physical signs of abuse should always raise a possibility of OI. Trial registration number: POG9440

Postinduction Supportive Care of Pediatric Acute Myelocytic Leukemia: Should Patients be Kept in the Hospital?

Children with AML become profoundly neutropenic while they undergo remission induction chemotherapy. It is unknown whether these children should be kept in the hospital while they are severely neutropenic to prevent life-threatening complications associated with neutropenia and reduce fatality. We at our institution routinely discharge patients after completing remission induction chemotherapy in the presence of profound neutropenia, unless it is clinically contraindicated. We reviewed all AML patients who were consecutively treated at our hospital from 1989 to 2011. Thirteen patients were electively discharged after completion of induction I chemotherapy. Of the 13, 4 died due to relapse or complications of stem cell transplants (not due to neutropenia related complications). Another eight are long term survivors. In this very small series, discharge from the hospital even though patients were severely neutropenic did not adversely affect the survival.

Clear cell sarcoma of the jaw: A case report and review of the literature

Clear cell sarcoma (CSS) is a unique malignant soft tissue tumor that mainly occurs from the aponeurotic tissue and tendons of extremities. It is rare in the pediatric population. The tumor does not respond well to chemotherapy or irradiation. Complete surgical resection offers the best chance for a cure. Most studies have demonstrated poor prognosis of this tumor, if it is >5 cm. The literature suggests that local recurrence and distant metastasis are not uncommon even with wide resection and that late recurrence and metastasis commonly occur. This case report discusses CSS in the jaw of a pediatric patient. To our knowledge, this is the only case of CSS of the jaw.

EBV Infection Resulting in Aplastic Anemia: A Case Report and Literature Review

We describe a three year old girl who developedconcurrent with reactivation of EBV infection. Literature review yielded a list of 23 cases of documented EBV infection with aplastic anemia. Though acyclovir was used as one of the treatment modality in many cases including ours, its effectiveness is unclear. It would be beneficial to develop EBV associated aplastic anemia registry to prospectively evaluate Acyclovir’s effectiveness. Also evaluation for evidence of EBV infection in all cases of idiopathic aplastic anemia would be useful.

Bone marrow necrosis as a presenting feature of childhood acute lymphoblastic leukemia

the abdomen revealed the presence of two small, peripheral abscesses in spleen suggestive of Candida infection. One week after starting VRC, LAmB was added (5 mg/kg/day). Two weeks later the boy became afebrile but the follow-up CT demonstrated the same number of detectable lesions in the lungs while the follow-up ECHO scan showed disappearance of the two lesions of the spleen. The combined antifungal treatment with VRC and LAmB was replaced by caspofungin (1.6mg/kg/day i.v). Patient’s clinical condition improved. The follow-up CT of the chest on day 50 was normal as also the laboratory tests (Candida Ag test and blood culture were negative) (Fig. 1B). Caspofungin was continued at a dosage of 1.6 mg/kg/die i.v for a total of 78 days. For the last 22 days caspofungin was given daily on an outpatient basis during antifungal treatment. No severe clinical and laboratory side effects were noted. The patient is in an excellent condition and has completed consolidation treatment. Caspofungin represents a antifungal agent with in vitro activity against Candida and Aspergillus species. Although there are many data about its combination with VRC or LAmB for invasive fungal infections, there are only few reports about the use of caspofungin as monotherapy in pediatric patients [1,4]. We conclude from our case that caspofungin given as a single agent was likely able to overcome all mycotic lesions in comparison to the combined antifungal treatment (VRC plus LAmB). It is, therefore, suggested that caspofungin be studied further as a consideration as monotherapy for aggressive mycotic disease.

Rothmund-Thomson syndrome (RTS) with osteosarcoma due to RECQL4 mutation

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder with clinical features consisting of poikiloderma, skeletal abnormalities, sparse hair, absent or scanty eyelashes and eyebrows and short stature. Patients with RTS due to genetic mutations of RECQL4 genes carry a high risk of developing osteosarcoma during childhood. Because of this, early genetic diagnosis is important. Here, we describe a 14-year-old white boy who developed an erythematous rash on both cheeks before the age of 3 months and was noted to have absent eyelashes and scanty eyebrows. He was found to have compound heterozygous mutations of the RECQL4 gene alleles at the age of 6 months and was diagnosed to have RTS type II. He subsequently developed osteosarcoma at age 10 which was successfully treated, and currently he has been tumour free for over 3 years.

Chronic myelomonocytic leukemia (CMML) as a second malignancy following Ewing sarcoma

To the Editor: Le Deley et al. [1], in Pediatric Blood & Cancer, reported a high frequency of secondary leukemia, including MDS and AML, following treatments with high cumulative doses of etoposide. Recently we cared for a child who developed CMML following etoposide-containing chemotherapy for Ewing sarcoma/ primitive neuroectodermal tumor (PNET). A 5-year-old African-American male developed an occipitoparietal mass. The tumorwas located in the scalp, and did not invade the calvarium. Excisional biopsy of the mass was read as Ewing sarcoma/PNET. There were no metastases. Cytogenetic analysis of the tumor cells was normal [no t(11;22) or t(21;22)]. Awide margin resection of the tumor was done and he was treated with chemotherapy on the COG AEWS 0031 protocol consisting of vincristine, doxorubicin, cyclophosphamide, and etoposide (total cumulative dose of etoposide, 3.55 g/m). About three years later, the patient developed leukocytosis (18,200/mL), monocytosis (12,078/mL), and mild anemia (Hb of 11 g/dL). Bone marrow revealed increased cellularity and myeloid hyperplasia with occasional myeloblasts. The chromosomal study demonstrated 100% of the cells to have 45, XY,-7. Chromosome 11 was intact. Flow cytometry showed CD13þ, CD 14þ, CD 15þ, and CD 33þ cells. Fetal hemoglobin was less than 1%. The diagnosis of chronic myelomonocytic leukemia (CMML) was made. The subsequent course over the next 2 years was a decrease of the platelet count to 60,000/mL and monocytosis (5,664/mL) and leukocytosis (23,600/mL). The patient remains asymptomatic and is awaiting a suitable unrelated stem cell donor. CMML is rare as a second neoplasm. Dose intense use of etoposide has been linked to an increased incidence of AML with translocation of the MLL gene [1]. On the other hand, a monosomy 7 or 7qabnormality has also been commonly found in treatment-associated leukemias [2]. The cause of the secondary myeloproliferative syndrome in our patient remains unclear.

Variceal hemorrhage 13 years after nephrectomy for Wilms tumor.

Wilms tumor accounts for most renal neoplasms in children (1). The treatment for a unilateral tumor is nephrectomy even if pulmonary metastases are present (1,2). An anterior peritoneal exploration is performed through a generous supraumbilical transverse abdominal incision and complete abdominal exploration permits evaluation for possible metastatic disease (1,2). For tumors of the left kidney, reflection of the spleen and the pancreas medially may be necessary to permit excision of large tumors arising in the upper pole of the kidney. This maneuver increases the risk of vascular complications associated with nephrectomy (3). Splenic vein thrombosis (SVT) results in left-sided portal hypertension, which leads to gastric or gastroesophageal varices and the consequent potential for massive hemorrhage (4,5). Surgical complications of nephrectomy for Wilms tumor include ligation or injury to major blood vessels, intestinal obstruction, injuries to other visceral organs including the spleen, pancreas, liver and intestine, deep venous thrombosis, pulmonary embolism and pancreatitis (3). However, to the best of our knowledge, sinistral portal hypertension with resultant variceal hemorrhage has not been reported in the literature. We present a 16-year-old boy who developed massive hematemesis 13 years after left nephrectomy for Wilms tumor. The patient had mild thrombocytopenia and leukopenia of unknown etiology for approximately 8 years before onset of hematemesis.