Non‐Hodgkin lymphoma following temozolomide

Temozolomide (TMZ) is an oral alkylating agent with significant activity against glioblastoma multiforme (GBM) and melanoma. It increases survival by 2.5 months when used in combination with radiotherapy as an adjuvant therapy in GBM. Secondary MDS/AML or non‐Hodgkin lymphoma attributed to TMZ exposure has been reported. We report a case of non‐Hodgkin lymphoma secondary to temozolomide in a 20‐year‐old female who was treated for GBM with concurrent TMZ and radiotherapy. She developed lymphoma 2 months after completing chemoradiotherapy. Although she was treated with combination chemotherapy for lymphoma, she died of progressive GBM. Pediatr Blood Cancer 2009;53:661–662. © 2009 Wiley‐Liss, Inc.     

Ifosfamide‐induced encephalopathy and movement disorder

Ifosfamide is a widely used chemotherapeutic agent for the treatment of a broad spectrum of solid tumors. CNS toxicity is a well‐described side effect of ifosfamide, but the mechanism of ifosfamide‐induced neurotoxicity remains poorly defined. We present two pediatric cases of hemiballismic limb movements in the setting of ifosfamide‐associated encephalopathy. To our knowledge, there have been no prior reports of ifosfamide‐induced hemiballism in pediatric patients. One of our patient's encephalopathy and abnormal movements may have improved after the administration of methylene blue and thiamine. Pediatr Blood Cancer 2010;54:624–626. © 2009 Wiley‐Liss, Inc.     

The effects of gender on health‐related quality of life in pediatric live‐donor kidney transplantation: A single‐center experience in a developing country

El‐Husseini A, Hassan R, Sobh M, Ghoneim M. The effects of gender on health‐related quality of life in pediatric live‐donor kidney transplantation: A single‐center experience in a developing country.
Pediatr Transplantation 2010:14:188–195. © 2009 John Wiley & Sons A/S. Abstract: To evaluate the effects of gender on HRQOL and overall health status in our pediatric kidney transplants. We performed a cross‐sectional study in 77 children who received living renal allo‐transplants in our center between 1981 and 2003. The patients were given a questionnaire at a post‐transplant visit. After completing, the patients returned it in a closed envelope. The questionnaire included demographic questions plus 57 multiple‐choice questions designed to analyze various aspects of post‐transplant life. Overall, the patients show satisfactory HRQOL. Most of the patients lived with their parents (79.2%). The current health status did not cause difficulties at work in 70.1% and did not interfere with the social life in 62.3% of patients. Physical and sexual growth was delayed in 48% and 85.7% of patients, respectively. A total of 67.5% of patients had normal health life or minor symptoms with normal activity. There was no significant effect of gender on HRQOL except for onset of puberty, sexual function, practicing sports, and obesity. Overall, the patients show satisfactory HRQOL. There was mild significant effect of gender on HRQOL. These findings may help health care professionals to develop gender‐specific interventions to optimize HRQOL of kidney transplants.     

Non‐sibling hematopoietic stem cell transplantation using myeloablative conditioning regimen in children with Maroteaux‐Lamy syndrome: A brief report

Maroteaux‐Lamy syndrome is a rare inherited lysosomal storage disorder with a progressive course. HSCT is a curable option for treatment in these patients. The following report describes our experience in HSCT for three patients with Maroteaux‐Lamy syndrome using non‐sibling donors. All of the patients received the same myeloablative regimen consisting of intravenous busulfan, cyclophosphamide, and rabbit antithymocyte globulin. Patients underwent HSCT from haploidentical other‐related (n=1), full‐matched other‐related (n=1), and one‐locus‐mismatched unrelated donor. Stem cell sources included bone marrow (n=1), peripheral blood (n=1), and cord blood (n=1). Currently, two patients who received transplant from other‐related donors showed full engraftment and regression of the symptoms of the disease, while for the patient with unrelated cord blood donor, graft failure resulted in progression of the disease and death. The result of our study showed beneficial effects of HSCT even from heterozygote donor. Due to rarity of the disease, future multicenter studies are recommended to find the best treatment approaches based on the patients’ status.     

Latissimus dorsi muscle‐flap over Gore‐Tex patch for coverage of large thoracic defects in paediatric Ewing sarcoma

Primary rib involvement accounts for 16% of paediatric Ewing sarcoma (ES). Neo‐adjuvant chemotherapy and surgical tumor resection may leave large thoracic wall defects requiring complex reconstruction in a growing individual. We report our experience in three children aged 3, 10, and 12 years, in whom single‐stage resection and reconstruction were performed using a Gore‐Tex Dualmesh patch, covered by a latissimus dorsi rotation flap harvested in continuity with the thoracolumbar fascia. The youngest patient also had a vertical expandable prosthetic titanium rib (VEPTR) anchored to help prevent subsequent scoliosis throughout growth. Pediatr Blood Cancer 2009;52:679–681. © 2009 Wiley‐Liss, Inc.     

Radiation‐induced skin cancer in humans*

The principal epidemiologic studies of ionizing radiation and skin cancer have all shown that radiation causes basal cell carcinoma but have not found dose‐related excesses of squamous cell carcinoma or malignant melanoma. The Japanese atomic bomb study indicates that doses of radiation under about 1 Gy confer less risk per unit dose than higher doses do. All available studies show that skin cancer risk is greater from radiation exposure at young ages than at older ages. Finding few excess skin cancers among irradiated African‐Americans as compared to Caucasians with a comparable dose indicates that skin susceptibility to ultraviolet exposure modifies the excess risk from ionizing radiation. Available evidence indicates that the excess risk of skin cancer lasts for 45 years or more following irradiation. Several studies indicate a risk of nonmelanoma skin cancer (NMSC) following cancer therapy; however, most of the studies reporting on NMSC have not distinguished between patients who received radiotherapy versus chemotherapy. Some, but not all, follow‐up studies of cancer patients have reported excesses of malignant melanoma as second malignant neoplasms. It is not clear from the studies how much, if any, of the excess melanoma risk is attributable to radiotherapy. Med. Pediatr. Oncol. 36:549–554, 2001. © 2001 Wiley‐Liss, Inc.     

Irinotecan as maintenance therapy in high‐risk hepatoblastoma

Children with high‐risk hepatoblastoma (metastatic disease or a low alpha‐fetoprotein at presentation) and those with recurrent disease have an extremely poor prognosis and are in need of novel therapeutic agents and strategies. We describe three patients who were treated with irinotecan (two in combination with vincristine). In two patients, this contributed to a clinical remission. All three patients received a 1‐ to 2‐year course of irinotecan as maintenance therapy and all remain disease free. Treatment was well tolerated with minimal toxicity. Further evaluation of the use of irinotecan as maintenance therapy in high‐risk and recurrent HB patients is warranted. Pediatr Blood Cancer 2010;54:761–763. © 2009 Wiley‐Liss, Inc.     

Pre‐freeze and post‐thaw characteristics on chimerism patterns in double‐unit cord blood transplantation

We analyzed the pre‐freeze and post‐thaw characteristics on chimerism patterns in 20 cases of double‐unit cord blood transplantation. The cord blood units (CBUs) were a 4/6 HLA match or better with recipients and achieved a minimum combined precryopreservation cell dose of 3.7 × 10⁷ total nucleated cell (TNC)/kg. The unit with a higher cell dose was infused first. All evaluable patients engrafted at a median of 18 days. By day 42, neutrophil engraftment was derived from both donors in 63% of cases and a single donor in 37% of patients. By day 100, one unit predominated in 80% of the patients. Higher pre‐freeze TNC and CD34+ cell doses were associated with cord predominance in 67% of patients. Pediatr Blood Cancer 2009;52:547–550. © 2008 Wiley‐Liss, Inc.     

Post‐transplant EBV‐related lymphoproliferative disorder complicating umbilical cord blood transplantation in patients of adrenoleukodystrophy

EBV‐associated post‐transplant lymphoproliferative disorder (PTLD) is a well‐recognized complication following solid organ transplantation and hematopoietic stem cell transplantation (HSCT) using bone marrow or peripheral blood as stem cell sources, but rarely reported in umbilical cord blood transplantation (UCBT). We report two cases in unrelated UCBT setting and added the following new information to the literature: (i) EBV‐related PTLD can be presented late in recipients of unrelated UCBT; (ii) in contrast to reported literatures that PTLD is a serious complication with unfavorable outcome, especially in monomorphic form, our cases showed that the clinical course may be relatively benign if treatment is initiated promptly. Pediatr Blood Cancer 2009; 53:1329–1331. © 2009 Wiley‐Liss, Inc.     

Closure of aortopulmonary window using Nit‐Occlud® PDA‐R device in a 3‐month‐old infant

Aortopulmonary window (APW) is a rare abnormality in which a pulmonary defect exists between the ascending aorta and the main pulmonary artery. Given that it may result in cardiac failure and pulmonary vascular disease in the early period, treatment needs to be performed without delay. In addition to surgical treatment, transcatheter closure may also be performed for selected patients. This study describes the case of an infant diagnosed with APW and who underwent successful transcatheter closure using a Nit‐Occlud_®PDA‐R device.     

Low‐dose total‐body irradiation and alemtuzumab‐based reduced‐intensity conditioning regimen results in durable engraftment and correction of clinical disease among children with chronic granulomatous disease

HSCT with MAC is associated with durable donor engraftment for patients with CGD; however, MAC is limited by high rates of RRT. We used a novel RIC regimen with LD‐TBI (200 cGy × two doses), fludarabine (30 mg/m² × three doses), and proximal alemtuzumab (0.5 mg/kg/dose × one dose) and unrelated donor grafts for consecutive patients with high‐risk CGD who were not candidates for MAC at our institution. Among four children with CGD transplanted at our institution, three PBSC recipients are alive with sustained donor engraftment (median follow‐up: two yr) and resolution of pre‐HSCT active infections while one patient with bone marrow graft is alive after graft failure and autologous recovery. RIC may be a curative option for children with high‐risk CGD.     

Comparison of outcomes after HLA‐matched unrelated and αβ T‐cell‐depleted haploidentical hematopoietic stem cell transplantation for children with high‐risk acute leukemia

T‐cell‐depleted HAPLO HSCT is an option to treat children with high‐risk acute leukemia lacking an HLA‐identical donor. We reviewed the outcome of children with acute leukemia after HAPLO (n = 21) and HLA‐MUD (n = 32) transplantation. The proportion of patients with ≥CR2 was significantly higher in HAPLO transplantation than MUD transplantation. Patients with MUD transplantation were significantly higher ABO incompatible than patients with HAPLO transplantation. There was no difference between the 2 groups in terms of engraftment, aGvHD and cGvHD, VOD, hemorrhagic cystitis, infections, and relapse. The 5‐year OS of MUD transplantation and HAPLO transplantation groups was found 65.8% and 71.1%, respectively (log‐rank 0.51). The 5‐year RFS was 80.7% for MUD transplantation group and 86.9% for HAPLO transplantation group (log‐rank 0.48). There was no statistically significant difference between 2 groups according to TRM (25% MUD transplantation vs 16.3% HAPLO transplantation, log‐rank 0.48). These data suggest that survival for patients with high‐risk acute leukemia after HAPLO transplantation with ex vivo ɑβ⁺ T‐cell depletion is comparable with MUD transplantation.     

Type 2 diabetes in a 5‐year‐old and single center experience of type 2 diabetes in youth under 10

The worrisome rise in pediatric type 2 diabetes (T2DM) is most prevalent among minority ethnic/racial populations. Typically, T2DM occurs during puberty in high risk obese adolescents with evidence of insulin resistance. Screening for T2DM in obese youth can be a daunting task for pediatricians and differentiating between pediatric T1DM and T2DM in obese youth can be challenging for pediatric endocrinologists. There is very limited data regarding the prevalence of T2DM among youth < 10 years of age. Here we present the case of a 5‐year‐old Hispanic male diagnosed with T2DM after referral by his pediatrician for abnormal weight gain, acanthosis nigricans and an elevated HbgA1c. He subsequently became symptomatic for diabetes with confirmed hyperglycemia and HbgA1c of 9.7% (83 mmol/mol) at the time of formal diagnosis. Type 1 diabetes autoantibodies (GAD65, Islet, and ZincT8) and monogenic diabetes genetic tests were negative. Due to elevated liver enzymes and baseline HbgA1c, he received basal insulin as his initial therapy. In this paper, we will discuss this case and present an IRB approved retrospective review of the characteristics of the 20 T2DM patients <10 years of age identified to date in our pediatric diabetes center. This review highlights that while uncommon, the diagnosis of T2DM merits consideration even in prepubertal children. This is especially true when working with a high risk population, such as our Hispanic South Texas youth.     

Hypercalcemia and osteoblastic lesions induced by 13‐Cis‐retinoic acid mimicking relapsed neuroblastoma

A 6‐year‐old male diagnosed with extensive neuroblastoma was treated with chemotherapy, surgery, autotransplantation, and radiotherapy. He was then enrolled on a study to assess the monoclonal antibody Ch14.18 (anti‐GD2) with 13 cis‐retinoic acid. 13‐cis‐retinoic acid therapy caused severe bone pain and hypercalcemia. Bone scans showed multiple osteoblastic lesions suggesting recurrent disease however MIBG scans were negative. Serum markers of bone turnover were increased and the patient required pamidronate therapy to treat persistent hypercalcemia. Retinoic acid toxicity needs to be considered in the differential of painful osteoblastic lesions and/or hypercalcemia. MIBG scans can assist in differentiating from recurrent disease. Pediatr Blood Cancer 2009;53:666–668. © 2009 Wiley‐Liss, Inc.     

Phase‐1 study of siplizumab in the treatment of pediatric patients with at least grade II newly diagnosed acute graft‐versus‐host disease

Brochstein JA, Grupp S, Yang H, Pillemer SR, Geba GP. Phase‐1 study of siplizumab in the treatment of pediatric patients with at least grade II newly diagnosed acute graft‐versus‐host disease.
Pediatr Transplantation 2010:14:233–241. © 2009 John Wiley & Sons A/S. Abstract: In a phase‐1 study, siplizumab, a humanized anti‐CD2 monoclonal antibody, was administered (0.012 or 0.04 mg/kg) to 10 pediatric patients with ≥ grade‐II newly diagnosed, non‐steroid‐refractory aGvHD after BMT or PBSCT. SAEs and other AEs including infections, and GvHD staging changes (overall, skin, liver, gut) were evaluated over 364 days. Patients reported a total of 121 AEs (19 grade‐3, 5 grade‐4 0.012 mg/kg group; 17 grade‐3, 17 grade‐4 0.04 mg/kg group) and 14 SAEs (five grade‐3, three grade‐4, 0.012 mg/kg group; three grade‐3, 0.04 mg/kg group); 15 AEs in five patients and four SAEs in three patients (fever, PTLD, adenoviral infection, and EBV lymphoma) were considered siplizumab‐related. Six deaths occurred (study days 17–267); two were considered siplizumab‐related: one from EBV‐associated PTLD (0.012 mg/kg) and one from adenoviral infection (0.04 mg/kg); the other four deaths could potentially be attributed in part to study drug Three patients (one, 0.012 mg/kg group; two, 0.04 mg/kg group) developed PTLD. By study day 12, GvHD grade decreased in 3/5 and 2/5 patients in the 0.012 and 0.04 mg/kg groups, respectively; remission (grade 0) occurred in one patient in each group. Four of five patients (0.012 mg/kg group) and one of four patients (0.04 mg/kg group) achieved grade 0 GvHD during the first 100 study days (55.6% response). While treatment with siplizumab was associated with improvement of GvHD and remission in some pediatric patients, the overall high morbidity, mortality, and occurrence of PTLD is of safety concern, not warranting further development of siplizumab for the treatment of aGvHD in children.     

Acute chest syndrome in the setting of SARS‐COV‐2 infections—A case series at an urban medical center in the Bronx

New York City has emerged as one of the epicenters of the SARS‐COV‐2 pandemic, with the Bronx being disproportionately affected. This novel coronavirus has caused significant respiratory manifestations raising the concern for development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD). We report a series of pediatric SCD SARS‐COV‐2‐positive patients admitted with ACS. SARS‐COV‐2‐positive SCD patients, who did not develop ACS, were the comparison group. Hydroxyurea use (P‐value = .02) and lower absolute monocyte counts (P‐value = .04) were noted in patients who did not develop ACS. These preliminary findings need to be further evaluated in larger cohorts.     

Survey of long‐term follow‐up programs in the United States for survivors of childhood brain tumors

Introduction

Despite recognition that childhood brain tumor survivors often suffer multiple late effects following therapy, little is known regarding the long‐term follow‐up (LTFU) programs for these patients.

Methods

A 16‐question survey was mailed to member institutions of the Children's Oncology Group in the United States. Institutions were asked about the size of their brain tumor program, activities of the LTFU programs and perceived barriers to follow‐up.

Results

One hundred forty‐five (74%) of 197 institutions returned surveys. Care for patients <21 years old at diagnosis who are >2 years following completion of therapy was provided at a designated neuro‐oncology LTFU clinic (31.2%), a general LTFU program for childhood cancer survivors (30.4%), or a general pediatric oncology program (29.7%). Institutions with a neuro‐oncology LTFU clinic were more likely to use neuro‐psychological testing following radiation therapy (P = 0.001), have longer duration of continued surveillance imaging (P = 0.02), use growth hormone replacement for medulloblastoma survivors (P < 0.001) and continue the use of growth hormone into adulthood (P = 0.05) than those with a general pediatric oncology program. Perceived barriers to care of brain tumor survivors included limited access and lack of insurance (32.1%), lack of funding or dedicated time for providers (22.9%), patients' uncertainty about need to follow‐up (20.6%), and patients' desire to not be followed in a pediatric cancer program (12.2%).

Conclusions

Considerable variation exists across institutions in the United States in the delivery of follow‐up care for survivors of childhood brain tumors. We encourage additional investigation to better define and implement optimal follow‐up care for childhood brain tumor survivors. Pediatr Blood Cancer 2009; 53:1295–1301. © 2009 Wiley‐Liss, Inc.     

Treatment with sirolimus ameliorates tacrolimus‐induced autoimmune cytopenias after solid organ transplant

The development of autoimmune blood cell cytopenias is a potentially life‐threatening complication of solid organ transplantation, resulting from T‐cell dysregulation from immunosuppressive medications. Conventional treatment with corticosteroids and IVIgG is often unsuccessful as these therapies are unlikely to overcome the T‐cell dysregulation. We describe two patients who developed severe autoimmune cytopenias after solid organ transplantation. They had limited response to conventional medications, but had complete resolution of autoimmunity upon transition of immunosuppression from tacrolimus to sirolimus. Altering the immunosuppressive regimen to modify T‐cell dysregulation may be beneficial for patients who develop post‐transplant autoimmune disease and allow continued preservation of allograft. Pediatr Blood Cancer 2009;53:1114–1116. © 2009 Wiley‐Liss, Inc.     

Determination of T‐cell subpopulations and intracellular cytokine production (interleukin‐2, interleukin‐4, and interferon‐γ) by cord blood T‐lymphocytes of neonates from atopic and non‐atopic parents

This report describes the results of a prospective study on immunological markers in cord blood for the prediction of allergic diseases in children. First we evaluated methodological aspects of the flow cytometric technique on cord blood cytokine measurements. Subsequently, the T‐cell subsets and percentage of cytokine‐producing cord blood T‐helper (Th) and T‐suppressor/cytotoxic lymphocytes of neonates from atopic and non‐atopic parents were compared. A group of 33 healthy, full‐term newborn infants of whom 23/33 were at risk for atopy (i.e. having at least one parent with one or more atopic symptoms and positive specific immunoglobulin E [IgE] to at least one common inhalant allergen) was studied. A flow cytometric technique was used to analyze cord blood T‐cell subsets and to determine the percentage of interleukin (IL)‐2‐, IL‐4‐, and interferon‐γ (IFN‐γ)‐producing cord blood Th and T‐suppressor/cytotoxic lymphocytes following stimulation with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. The percentage of CD3 (T lymphocytes), CD3⁺ CD4⁺ (Th lymphocytes), CD3⁺ CD8⁺ (T‐suppressor/cytotoxic lymphocytes), CD19⁺ (B lymphocytes), CD3⁺ CD4⁺ CD45RO⁺ (memory Th lymphocytes), and CD3⁺ CD4⁺ CD45RA⁺ (naive Th lymphocytes) cells was unrelated to parental atopic status. PMA stimulation augmented the percentage of IL‐2‐ and IFN‐γ‐producing Th and T‐suppressor/cytotoxic lymphocytes, whereas the number of IL‐4‐producing T lymphocytes remained very low or undetectable. No differences in the percentage of IL‐2‐, IL‐4‐ and IFN‐γ‐producing Th and T‐suppressor/cytotoxic lymphocytes were found between neonates from atopic and non‐atopic parents. These results will be re‐evaluated when the atopic status of the children at the age of 1 and 2 years can be assessed.     

Congenital aggressive variant of Langerhans cells histiocytosis with CD56+/E‐Cadherin− phenotype

In children <2 years of age, cutaneous involvement is the most frequent presentation of Langerhans cell histiocytosis (LCH). Cutaneous LCH can be localized or associated with dissemination and organ dysfunction. The clinical course is variable, ranging from spontaneous regression to a fatal outcome. We describe a female newborn presenting with congenital cutaneous lesions who rapidly developed pulmonary infiltrates and multiple osteolytic lesions. Skin biopsy showed a dermal infiltrate of medium to large cells morphologically and phenotypically consistent with LCH. The clinical course was rapidly fatal in spite of chemotherapy. No strict correlation between morphology and prognosis has been documented in LCH, but, in our case, distinct morphological and immunohistochemical features (CD56 expression and no E‐Cadherin expression) may have contributed to an aggressive clinical course. Pediatr Blood Cancer 2009;53:1107–1110. © 2009 Wiley‐Liss, Inc.