Nasopharyngeal carcinoma in Turkish children: review of 33 cases.

A retrospective and prospective analysis is reported of epidemiological, clinical, and therapeutic aspects of 33 children with nasopharyngeal carcinoma who were treated in a single institution over a period of 10 years. Twenty-three male and 10 female children ranging from 9 to 17 years were referred to our center. Histopathology was WHO type 3 carcinoma in 21, WHO type 2 in 8, WHO type 1 in 1, and unclassified in 3 patients. Disease extent was T2a (n = 15), T2b (n = 2), T3 (n = 11), and T4 (n = 5); N1 (n = 5), N2 (n = 12), and N3a (n = 16). Five patients had base of skull invasion. Four patients had M1 disease on admission. Four patients were treated with irradiation only. Three patients received neoadjuvant, 4 patients received adjuvant, and 22 patients received neoadjuvant + adjuvant chemotherapy in addition to radiotherapy. Patients received 50-72 Gy to the primary tumor and involved nodes and 45-50 Gy to uninvolved regions. Chemotherapy consisted of combinations of cisplatin, fluorouracil or Adriamycin, vincristine, and cyclophosphamide. Twenty-nine patients (88%) attained locoregional control. Overall, 10 patients died with progressive disease or infectious complications, and 2 patients are still receiving therapy. Three patients are still living with multiple metastases and stable disease. Eight patients were lost to follow-up. Twelve patients are alive without relapse 3 and 63 months from diagnosis. Seven patients had 6 relapses at distant and 1 relapse at local site. The median time for first relapse was 8 months. Overall, the 5-year survival rate was 63% and disease-free survival rate was 53%. Although the locoregional control rate is high, long-term survival rates will be the real test of the impact of chemotherapy. Further studies are needed to confirm the optimal combination of effective chemotherapeutic agents and radiotherapy.     

Central nervous system relapse of rhabdomyosarcoma

1 Purpose

The optimal management of central nervous system (CNS) relapse of rhabdomyosarcoma (RMS) is unclear. We examined diagnosis, management, and outcomes of patients with RMS developing CNS relapse.

2 Methods

Records of 23 patients diagnosed with CNS relapse between 1999 and 2016 were reviewed. Median age at presentation of CNS relapse was 15 years (range, 1–34 years). High‐risk features at initial presentation were as follows: 16 alveolar patients, 13 Stage IV, and 13 with primary tumor in parameningeal locations.

3 Results

CNS relapse occurred at a median 12 months (range, 1–23 months) from diagnosis and most common presenting symptoms were headache (n = 9), nausea/vomiting (n = 8), visual difficulty (n = 5), and none (n = 5). Leptomeningeal metastases were detected in 21 patients while only 2 developed parenchymal metastases without leptomeningeal involvement. Fifteen patients received CNS‐directed radiation therapy (RT), including craniospinal irradiation to a median 36 Gy (range, 18–36 Gy) and/or whole brain radiotherapy to a median 30 Gy (range, 6–41.4 Gy). Three patients received concurrent chemotherapy. Follow‐up magnetic resonance imaging was conducted in 13 patients after RT initiation with 8 demonstrating improvement, 2 with stable disease, and 3 with progression. Twelve patients were tested for reactivity to I‐131‐labeled monoclonal antibody 8H9, and three tested positive and received at least one intra‐Ommaya dose; all three lived >12 months post‐CNS relapse. Twenty‐one patients died of CNS disease and two of metastatic disease at other sites. Median survival post‐CNS relapse was 5 months (range, 0.1–49 months).

4 Conclusions

The prognosis for patients with RMS developing CNS relapse remains poor. Treatment including CNS‐directed RT should be considered and investigation into preventative therapies is warranted.     

Extramedullary leukemia in children with acute myeloid leukemia: A population‐based cohort study from the Nordic Society of Pediatric Hematology and Oncology (NOPHO)

1 Background

The prognostic significance of extramedullary leukemia (EML) in childhood acute myeloid leukemia is not clarified.

2 Procedure

This population‐based study included 315 children from the NOPHO‐AML 2004 trial.

3 Results

At diagnosis, 73 (23%) patients had EML: 39 (12%) had myeloid sarcoma, 22 (7%) had central nervous system disease, and 12 (4%) had both. EML was associated with young age (median age: 2.6 years), a high white blood cell count (median: 40 × 10⁹/l), M5 morphology (40%), and 11q23/MLL (KMT2A) rearrangements (34%). No patient received involved field radiotherapy. Five‐year event‐free survival did not differ significantly between the EML and the non‐EML patients (54% vs. 45%, P = 0.57), whereas 5‐year overall survival (OS) was significantly lower in the EML group (64% vs. 73%, P = 0.04). The risk of induction death was significantly higher for EML patients (8% vs. 1%, P = 0.002). There was a trend toward a lower risk of relapse for EML patients (5‐year cumulative incidence of relapse 33% vs. 49%, P = 0.16). Traumatic lumbar puncture did not adversely affect survival in this cohort.

4 Conclusions

EML was associated with increased risk of induction death impacting the OS. No patients relapsed at the primary site of the myeloid sarcoma despite management without radiotherapy.     

Acute Lymphoblastic Leukemia and Klinefelter's Syndrome

Collins' law states that the period of risk for tumor recurrence is the age of the child at diagnosis plus 9 months. The purpose of this study is to validate this rule through a retrospective review of common pediatric tumors seen at 1 institution. Inclusion criteria for this study included an age at diagnosis of < 16 years old, minimum follow-up time of the Collins risk period (CRP) if child did not relapse and treatment with curative intent. The records of 424 children seen and treated for neuroblastoma (n = 98), Wilms tumor (n = 86), rhabdomyosarcoma (n = 82), medulloblastoma (n = 59), Ewing sarcoma (n = 43), ependymoma (n = 25), supratentorial PNET (n = 22), and synovial sarcoma (n = 9) from 1960 to 2001 were reviewed. CRP was calculated using the age of child at initial diagnosis plus 9 months. The median follow-up time was 164 months (range, 11–484 months), while the median follow-up/CRP ratio was 4.89 (range, 1.0–48.0). A total of 183 of 424 (43.2%) patients relapsed, with 180 (98.4%) relapses occurring during the CRP. Relapses beyond the CRP were seen in 3 young children (ages 7 months, 24 months, and 2 weeks at initial diagnosis) with a diagnosis of Wilms tumor (n = 2) and supratentorial PNET (n = 1) at 1, 3, and 26 months post-CRP. Collins' law is a useful and simple way of predicting risk period for relapse in the tumor types studied.     

Androgen therapy in Fanconi anemia: A retrospective analysis of 30 years in Germany

A substantial number of individuals with Fanconi anemia (FA) develop bone marrow failure and are treated with androgen therapy in order to increase blood counts. The authors retrospectively identified 70 patients who received androgen therapy any time between July 1976 and September 2014. Among these patients, 37 had medical records for analysis. Twenty-five of the 37 (68%) patients had response in hemoglobin level (n = 25), platelet count (n = 21), and/or absolute neutrophil count (n = 13). The median rise in hemoglobin was 6.5 mg/dL, platelet count 70,000/mm³, and absolute neutrophil count (ANC) 1530/μL. The majority of patients (n = 22) had a response in 2 or more blood parameters. Reasons for discontinuation of therapy included development of cytogenetic aberrations (n = 9), lack of response (n = 7), hepatic adenoma (n = 6), progression to myelodysplastic syndrome/acute myeloid leukemia (n = 3), stabilization of blood parameters (n = 3), resolution of cytopenia secondary to mosaicism (n = 1), virilization (n = 1), development of anogenital carcinoma (n = 1), inaccessibility of medication (n = 1), and unknown (n = 1). Four patients at last follow-up remain on androgen therapy. These results highlight that androgen therapy can significantly improve blood counts for many FA patients, but progression of underlying bone marrow disease and development of liver adenomas requires careful monitoring.     

Profiling Loss of Heterozygosity Patterns in a Cohort of Favorable Histology Nephroblastoma Egyptian Patients: What is Consistent With the Rest of the World

According to the Fifth National Wilms Tumor Study (NWTS-5), tumor-specific loss of heterozygosity (LOH) for chromosomes 1p and 16q identifies a subset of patients with Wilms tumor (WT) who despite having favorable histology (FH) have a significantly increased risk of relapse and death. We aimed to find out 1p and 16q LOH frequencies in patients with FH-WT as well as its correlation to survival outcome and epidemiologic and clinical characteristics. Data of patients with FH-WT presenting to the National Cancer Institute, Egypt, were retrospectively analyzed. Paraffin blocks were tested for 1p and 16q LOH using polymorphic loci that span the minimal regions of LOH at this area. The study included 100 patients with a median age of 5 years. Thirty-nine patients (39%) showed LOH at 1p (n = 14), 16q (n = 13), or both (n = 12). LOH was most frequently encountered in patients above 10 years (5/5), advanced stages disease (80% of stage V and 50% of stages IV and III each). The 3-year overall survival (OS) and event-free survival (EFS) were significantly lower in patients with double LOH (75% and 50%, respectively), followed by 16q (92% and 54%), in comparison with 1p (93% each) and negative LOH (97% and 100%) cases, respectively (p = 0.001). Combined LOH (1p+16q), followed by 16q LOH alone, was predictive of poorer outcome and was associated with lower OS and EFS in patients with FH-WT. Our results showed a higher-risk disease that would suggest the need for an intensified upfront therapy in this group of patients.     

Outcomes in childhood AML in the absence of transplantation in first remission--Children's Cancer Group (CCG) studies 2891 and CCG 213

Background

The majority of childhood acute myeloid leukemia (AML) patients lack a matched‐related bone marrow transplant (BMT) donor in first remission.

Procedure

Disease‐free survival (DFS), overall survival (OS), relapse‐free survival (RFS), and post‐relapse outcome were evaluated for children with de novo AML on CCG 213 and the standard timing (ST) and intensive timing (IT) induction arms of CCG 2891 who were randomized to (intent‐to‐treat, ITT) or who received (as‐treated, AT) only chemotherapy intensification.

Results

Outcomes at 8 years post‐induction in ITT analysis of chemotherapy intensification were as follows: 31% DFS, 43% OS on CCG 213; 34% DFS, 51% OS on CCG 2891 ST; 48% DFS, 56% OS on CCG 2891 IT. All toxic deaths during and following Capizzi II chemotherapy intensification on both protocols were in patients >3 years of age (P ≤ 0.001). Black race was a significant poor prognostic factor for OS (P = 0.008, hazard ratio: 1.74, 95% CI: 1.15–2.61). Overall 48% of patients on both trials relapsed and 19.1% of patients who relapsed on these trials survived. CR1 >12 months portends a much better OS for patients who relapse. Post‐relapse treatment included BMT in 47% of patients.

Conclusions

OS on CCG 2891 was superior to CCG 213 but equivalent between ST and IT arms due to better salvage rates post‐relapse in ST patients. Overall survival for childhood AML in the absence of BMT in CR1 is influenced by duration of CR1 and by race. Pediatr Blood Cancer 2008;50:9–16. © 2007 Wiley‐Liss, Inc.     

Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA‐identical related donors

Watanabe N, Takahashi Y, Matsumoto K, Horikoshi Y, Hama A, Muramatsu H, Yoshida N, Yagasaki H, Kudo K, Horibe K, Kato K, Kojima S. Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA‐identical related donors.
Pediatr Transplantation 2011: 15: 642–649. © 2011 John Wiley & Sons A/S. Abstract: Although some studies have reported that TBI and MEL offer an effective conditioning regimen for autologous SCT in acute leukemia, little has been reported regarding outcomes of allogeneic SCT. We retrospectively evaluated outcomes for 50 pediatric patients who underwent allo‐SCT conditioned with intravenous MEL (180–210 mg/m²) and fractionated TBI (12–13.2 Gy) from HLA‐identical related donors. Nineteen patients were in CR1, 18 were in CR2, and 13 showed advanced‐stage disease (≥CR3). Patients had received allo‐SCT from HLA‐identical siblings (n = 45) or phenotypically HLA‐identical family donors (n = 5). Median duration of follow‐up for all disease‐free patients was 61 months (range, 8.8–177 months). At the time of analysis, 12 patients had died. Eleven of those died of relapse, and one died of TRM. DFS rates for all patients, patients with AML (n = 12), and patients with lymphoid malignancy (n = 38) were 61.4% and 82.1%, respectively. DFS rates for CR1, CR2, and ≥CR3 cases were 89.2%, 88.1%, and 23.1%, respectively (p < 0.05). MEL/TBI for pediatric patients with hematological malignancies was associated with lower relapse rates and no increase in toxicity, resulting in better survival.     

Should healthy children who will undergo minor surgery be screened for coagulation disorder?

The objective of this study is to analyze the major causes of abnormal findings seen in the preoperative coagulation tests of asymptomatic pediatric patients and to discuss the usefulness of coagulation tests prior to minor surgery. Among patients who received minor surgery in Kyung Hee University Medical Center from March 2008 to April 2015, a total of 7114 pediatric patients (ages 1–18) were included in our study. Of these, 226 (3.1%) were referred to the pediatrics hematology-oncology department because of abnormal preoperative coagulation tests. A review of the coagulation tests indicate the majority (n = 216, 95.5%) have prolonged activated partial thromboplastin time (aPTT), whereas a smaller number (n = 10, 4.5%) have prolonged prothrombin time international normalized ratio (PT INR). When the coagulation tests were repeated, 136 displayed abnormal findings again. Of these 136 patients, 128 patients underwent mixing tests, and 127 showed results of correction and were composed as follows: normal (n = 83), subnormal (n = 26), factor deficiency (n = 15), and lupus anticoagulant positive (n = 3). Breakdown by factor deficiencies was as follows: (i) factor XII (n = 9), (ii) factor IX (n = 2), (iii) factors XII and IX (n = 1), (iv) factor VIII (n = 1), (v) factor XI (n = 1), (vi) von Willebrand factor (vWF; n = 1), and (vii) factor V (n = 1). Each factor activity range was mild (21%–39%), so no patients received preoperative medications or clotting factors/blood products. Even in the presence of factor deficiencies, bleeding symptoms were mild and postoperative complications did not occur. These results suggest that coagulation tests may not be needed in healthy children and should be reserved for patients with positive bleeding and/or family history.     

SINGLE-CENTER EXPERIENCE: Immunosuppressive Therapy as Frontline Treatment for 33 Children with Acquired Severe Aplastic Anemia

The authors retrospectively analyzed the records of 33 children with acquired severe aplastic anemia (SAA) diagnosed from July 1998 to October 2007 and first treated by immunosuppressive therapy (IST). Serial hematologic parameters, complications, transfusion requirements, and time to response were assessed. Allogeneic hematopoietic stem cell transplantation (HSCT) was attempted in 7 patients after failure of IST (n = 6) or relapse following an initial response to IST (n = 1). One child died of post-transplant lymphoproliferative disorder. Thirty of the 33 patients are alive and well after a median follow-up of 45 months (range, 7–116 months). Overall (transfusion-independent) response to IST was 73% (24/33). The actuarial 5 years survival rate was 89.4%. In this study, all patients with SAA received IST as standard front-line therapy. Approximately three-fourths of patients with SAA have durable recovery and excellent overall survival.     

Treatment results for patients with localized,completely resected (Group I) alveolar rhabdomyosarcoma on Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols III and IV, 1984–1997: A report from the Children's Oncology Group

Purpose

To assess local control, event‐free survival (EFS), and overall survival (OS) rates in 71 patients with localized, completely resected (Group I) alveolar rhabdomyosarcoma (ALV RMS) and their relation to radiation therapy (RT) on IRSG Protocols III and IV, 1984–1997.

Methods

Chart review and standard statistical procedures.

Patients and Tumors

Patients were 1–18 years at diagnosis (median, 6 years). Primary tumor sites were extremity/trunk (N = 54), head/neck (N = 9), genitourinary tract (N = 7), and perineum (N = 1). Thirty patients received VA ± C with RT; 41 received VA ± C alone. RT was assigned, not randomized.

Results

Fifty‐four patients had Stage 1 (favorable site, any size) or Stage 2 (unfavorable site, ≤5 cm) tumors. Eight‐year EFS was 90%, with 100% local control for 17 patients given RT. Eight‐year EFS was 88%, with 92% local control for 37 patients without RT; P = 0.52 for EFS comparisons, 0.3 for local control comparisons. In 17 Stage 3 patients (unfavorable site, tumors >5 cm, N0), 8‐year EFS was 84% with 100% local control in 13 patients given RT; 8‐year EFS was only 25% and local control 50% in 4 patients without RT. Local recurrence was the most common site of first failure in non‐irradiated patients.

Conclusion

Patients with Stage 1–2 ALV RMS had slightly but statistically insignificantly improved local control, EFS, and OS rates when local RT was given. The need for local RT in Stage 1–2 patients deserves evaluation in a randomized study. Local control, EFS, and OS rates were significantly improved in Stage 3 patients receiving local RT. Pediatr Blood Cancer. 2010;55:612–616. © 2010 Wiley‐Liss, Inc.     

Second-line treatment of pediatric patients with relapsed rhabdomyosarcoma adapted to initial risk stratification: Data of the European Soft Tissue Sarcoma Registry (SoTiSaR)

Background

Outcome of relapsed disease of localized rhabdomyosarcoma remains poor. An individual treatment approach considering the initial systemic treatment and risk group was included in the Cooperative Weichteilsarkom Studiengruppe (CWS) Guidance.

Methods

Second-line chemotherapy (sCHT) ACCTTIVE based on anthracyclines (adriamycin, carboplatin, cyclophosphamide, topotecan, vincristine, etoposide) was recommended for patients with initial low- (LR), standard- (SR), and high-risk (HR) group after initial treatment without anthracyclines. TECC (topotecan, etoposide, carboplatin, cyclophosphamide) was recommended after initial anthracycline-based regimen in the very high-risk (VHR) group. Data of patients with relapse (n = 68) registered in the European Soft Tissue Sarcoma Registry SoTiSaR (2009–2018) were retrospectively analyzed.

Results

Patients of initial LR (n = 2), SR (n = 16), HR (n = 41), and VHR (n = 9) group relapsed. sCHT consisted of ACCTTIVE (n = 36), TECC (n = 12), or other (n = 15). Resection was performed in 40/68 (59%) patients and/or radiotherapy in 47/68 (69%). Initial risk stratification, pattern/time to relapse, and achievement of second complete remission were significant prognostic factors. Microscopically incomplete resection with additional radiotherapy was not inferior to microscopically complete resection (p = .17). The 5-year event-free survival (EFS) and overall survival (OS) were 26% (±12%) and 31% (±14%). The 5-year OS of patients with relapse of SR, HR, and VHR groups was 80% (±21%), 20% (±16%), and 13% (±23%, p = .008), respectively.

Conclusion

Adapted systemic treatment of relapsed disease considering the initial risk group and initial treatment is reasonable. New treatment options are needed for patients of initial HR and VHR groups.     

Creation and Enlargement of Atrial Defects in Congenital Heart Disease

Transcatheter creation and enlargement of interatrial defects (IAD) may improve hemodynamics; however, procedural outcomes have not been well defined. Hospital records were reviewed for children who underwent percutaneous procedures to create and enlarge an IAD and were grouped as follows: (1) right and (2) left heart obstructive lesions, (3) left atrial (LA) decompression during left heart assist, (4) failing Fontan circulation, and (5) miscellaneous. Forty-five children (mean age, 3.4 ± 4.7 years; 30 (67%) male) were identified. In group 1 (n = 6), all achieved endpoints of right atrial (RA) decompression (n = 2), improved left ventricular filling (n = 3), or improved arterial saturations (n = 1). In group 2 (n =18), mean LA pressure decreased (21 ± 6 to 13 ± 5 mmHg, p < 0.001) and arterial saturations increased (61 ± 13% to 78 ± 11%, p < 0.001). All except 2 patients achieved definitive repair, further palliation (n = 9), or heart transplantation (HTX) (n = 7). In group 3 (n = 5), the LA was decompressed (21 to 13 mmHg, p = 0.03) in all, and all except 1 patient survived to HTX (n = 2) or full recovery (n = 2). In group 4 (n = 11), of 7 patients with a low cardiac output syndrome after surgery, despite improved atrial shunting, 3 died and 1 required a HTX. In group 5 (n=5), RA decompression (n = 1) or improved arterial saturation (n = 4) was achieved in all. Overall, 5-year HTX free survival was 75%. Mechanical ventilation before the procedure (p < 0.001), the need for a blade septostomy (p = 0.002), and higher LA pressures after the procedure (p = 0.04) independently predicted mortality or the requirement for HTX. Transcatheter optimization of an atrial communication can help optimize treatment strategies and has a low procedural risk.     

Central nervous system disease in pediatric acute myeloid leukemia: A report from the Children's Oncology Group

1 Background

The prognostic impact of central nervous system (CNS) involvement in children with acute myeloid leukemia (AML) has varied in past trials, and controversy exists over the degree of involvement requiring intensified CNS therapy. Two recent Children's Oncology Group protocols, AAML03P1 and AAML0531, directed additional intrathecal (IT) therapy to patients with CNS2 (≤5 white blood cell [WBC] with blasts) or CNS3 (>5 WBC with blasts or CNS symptoms) disease at diagnosis.

2 Methods

We examined disease characteristics and outcomes of the 1,344 patients on these protocols, 949 with CNS1 (no blasts), 217 with CNS2, and 178 with CNS3, with the latter two receiving additional IT therapy.

3 Results

Young age (P = 0.003), hyperleukocytosis (P < 0.001), and the presence of inversion 16 (P < 0.001) were the only factors more prevalent in patients with CNS2 or CNS3 disease. Complete remission at the end of induction (EOI) 2 was achieved less often in patients with CNS involvement (P < 0.001). From diagnosis, event‐free survival (EFS) for patients with CNS involvement was significantly worse (P < 0.001), whereas overall survival (OS) was not (P = 0.16). From the EOI1, there was a higher relapse rate (RR) and worse disease‐free survival (DFS), but less impact on OS (CNS1:DFS 58.9%, RR 34.1%, OS 69.3%; CNS2:DFS 53.2%, RR 40.9%, OS 74.7%; CNS3:DFS 45.2%, RR 48.8%, OS 60.8%; P = 0.006, P < 0.001, P = 0.045, respectively). Multivariable analysis showed that independently CNS2 and CNS3 status adversely affected RR and DFS. Traumatic diagnostic lumbar puncture was not associated with worse outcome.

4 Conclusions

CNS leukemia confers greater relapse risk despite more aggressive locally directed therapy. Novel approaches need to be investigated in this group of patients.     

An approach for cure: PEI-chemotherapy and regional deep hyperthermia in children and adolescents with unresectable malignant tumors

BACKGROUND: Elevated temperatures of 40 - 44 degrees C increase the actions of various anticancer drugs including N-lost derivatives, cytotoxic antibiotics and platinum analoga. In clinical usage thermochemotherapy (TCH) should facilitate surgical resection and ameliorate local tumor control. PATIENTS AND METHODS: From 07/1993 to 12/2002 a total of 39 patients have been enrolled onto a phase-II study (female = 24, male = 15, age 1 - 37.5 years, median 5.2). Among these, 24 patients had extracranial non-testicular germ cell tumors and 15 patients soft tissue or chondrosarcomas. Indication: locoregional relapse (n = 29) or unresectable tumor after neoadjuvant chemotherapy (n = 10). Among these two groups, there were ten patients with poor response or progressive disease under primary or relapse chemotherapy. Ten out of the 29 relapse patients had more than one relapse. Tumor site: pelvis (30), abdomen (4), head and neck (2), proximal leg (2) and lumbar spine (1). Thermochemotherapy (TCH): 1800 - 2000 mg ifosfamide/m (2) and 100 mg etoposide/m (2) on days 1 - 4 and 40 mg cisplatin/m (2) on days 1 + 4 combined with regional deep hyperthermia (42 - 44 degrees C, 1 h) on days 1 + 4. RESULTS: In 39 protocol patients a total of 166 TCH courses (332 heat sessions) were applied. 20 patients achieved complete response, and 10 patients achieved partial response. TCH was followed by surgical tumor resection in 28/39 patients and/or radiotherapy in 13/39 patients. At a median follow-up of 27 months, outcome in this high-risk patient population was 22 NED, 3 AWD, 12 DOD, 2 DOC. Five year event free (EFS) and overall survival (OS) for the whole study cohort was 0.39 +/- 0.11 (20/39 patients) and 0.52 +/- 0.11 (25/39 patients), respectively. CONCLUSION: TCH shows substantial therapeutic efficacy and facilitates complete tumor resection in 14 out of 28 operated patients. Multimodal treatment including TCH, surgical resection and/or radiotherapy leads to sustained remission in the majority of patients with locoregional tumor recurrence. The therapeutic effect is most pronounced, if TCH is administered at first relapse. Due to the clinical and histologic heterogeneity the number of patients eligible for TCH is limited. Therefore, a more valid assessment of treatment efficacy can only be made by a matched-pair comparison in cooperation with the clinical registers.     

Neonatal renal vein thrombosis: Role of anticoagulation and thrombolysis—An institutional review

Neonatal renal vein thrombosis (NRVT) is a rare thromboembolic complication in the neonatal period, and sequelae from renal dysfunction can cause significant morbidity. The authors retrospectively reviewed 10 patients with NRVT treated at their institution. The majority of the cohort were male (n = 9), preterm (n = 6), and had unilateral NRVT (n = 6). Six patients received thrombolysis and/or anticoagulation, and 4 patients received supportive care only. Two of the 6 patients treated with anticoagulation who had bilateral NRVT and anuria received thrombolysis with low-dose tissue plasminogen activator. Thrombolysis was not associated with any major adverse events, and both patients had marked improvement of renal function. Eight patients subsequently developed renal atrophy (3 received anticoagulation, 2 received thrombolysis with anticoagulation, and 3 received supportive care). Anticoagulation/thrombolysis did not appear to prevent renal atrophy. The role of thrombolysis needs to be further studied and considered in the setting of bilateral NRVT and acute renal failure.     

Lupus Anticoagulant Positivity in Pediatric Patients With Prolonged Activated Partial Thromboplastin Time: A Single-Center Experience and Review of Literature

The presence of lupus anticoagulants (LAs) is an important cause of activated partial thromboplastin time (aPTT) prolongation found in children after an infection or during screening tests before surgical intervention. The authors retrospectively reviewed the charts of 68 patients who have been consulted from surgery departments with prolonged aPTT. These patients were reevaluated with aPTT analysis after 1 week. Thirteen patients had normal aPTTs. Therefore, 55 patients remained with prolonged aPTTs. LA positivity was detected in 39 patients. Sixteen of these had prolonged aPTT prior to surgery (41%). Others with LA positivity had systemic lupus erythematosus (SLE; n = 6), infection (n = 5), leukemia (n = 3), hemolytic uremic syndrome (n = 2), epistaxis (n = 2), antiphospholipid syndrome (APS; n = 1), chronic immune thrombocytopenic purpura (n = 1), acute poststreptococcal glomerulonephritis (n = 1), central nervous system (CNS) thrombosis (n = 1), and congenital heart disease (n = 1). None of the patients had bleeding history. LA positivity rarely leads to bleeding and/or thrombosis. Specific therapy is usually not needed. Further prospective multicenter studies are required to understand clinical outcomes and laboratory correlation in children with positive LA.     

Dose‐escalation is needed for gross disease in high‐risk neuroblastoma

1 Background

Locoregional failure is common after subtotal resection in high‐risk neuroblastoma. Although a dose of 21 Gy radiation therapy (RT) is standard for treatment of high‐risk neuroblastoma after gross total resection, the dose needed for local control of patients with gross residual disease at the time of RT is unknown. We sought to evaluate local control after 21–36 Gy RT in patients with high‐risk neuroblastoma undergoing subtotal resection.

2 Methods

All patients with high‐risk neuroblastoma who received RT to their primary site from 2000 to 2016 were reviewed. Of the 331 patients who received consolidative RT to their primary site, 19 (5.7%) underwent subtotal resection and were included in our analysis. Local failure (LF) was correlated with biologic prognostic factors and dose of RT.

3 Results

Median follow‐up among surviving patients was 6.0 years. Median RT dose was 25 Gy (range, 21 Gy–36 Gy). The 5‐year cumulative incidence of LF among all patients was 17.2%. LF at 5 years was 30% in those who received <30 Gy versus 0% in those who received 30–36 Gy (P = 0.12). There was a trend towards improved local control in patients with tumor size ≤10 cm at diagnosis (P = 0.12). The 5‐year event‐free and overall survival were 44.9% and 68.7%, respectively.

4 Conclusion

After subtotal resection, patients who received less than 30 Gy had poor local control. Doses of 30–36 Gy are likely needed for optimal control of gross residual disease at the time of consolidative RT in high‐risk neuroblastoma.     

Surgical complications and outcome of paediatric liver transplantation: the Singapore experience

The purpose of this study was to analyse the early and late results of paediatric liver transplantation (LT), with particular reference to complications that required surgical intervention. The charts of all children who underwent LT between 1990 and 2002 were reviewed retrospectively. Results were analysed with a minimum follow up of 9 months. Thirty-five children have undergone 38 LTs; 22 received grafts from their parents, 16 received cadaveric organs and three children had retransplantation. The ages of the children ranged from 12 to 168 months. Biliary atresia was the most frequent indication for transplant (n=27). Twenty-seven children had complications that required surgical or radiological interventional procedures. Vascular complications included hepatic artery thrombosis (n=2), hepatic vein (HV) thrombosis (n=1), and the majority being portal vein thrombosis (n=6). Bile leaks were observed in eight children. Other complications included intestinal perforation (n=2), intra-abdominal abscesses (n=1), wound dehiscence (n=2), post-operative bleed (n=2), intestinal obstruction (n=2), ventral hernia (n=1), and multiple abdominal wound sinuses (n=1). Three children underwent retransplantation, two for hepatic artery thrombosis with multiple episodes of cholangitis and intrahepatic biliomas and the third was done for hepatic vein thrombosis. Patient and graft survival at 1 year is 81.5 and 74.2%, respectively. Paediatric LT is associated with significant morbidity, the main complications being vascular and biliary. The article was presented at the 8th Congress of the Asian Society of Transplanatation (8th CAST) in September 2003 held in Kuala Lumpur, Malaysia.     

Prognostic Factors for Outcome in Localized Extremity Rhabdomyosarcoma. Pooled Analysis from Four International Cooperative Groups

Background

Extremity rhabdomyosarcomas do not always show satisfactory outcomes. We analyzed data from 643 patients treated in 14 studies conducted by European and North American groups between 1983 and 2004 to identify factors predictive of outcome.

Procedure

Clinical factors, including age; histology; site of primary (hand and foot vs. other); size; invasiveness (T stage); nodal involvement (N stage); and treatment factors, including post‐surgical group; chemotherapy type and duration; radiotherapy; and treatment (before or after 1995); were evaluated for impact on overall survival (OS).

Results

5‐year OS were 67% (se 1.8). Multivariate analysis showed that lower OS correlated with age >3 years, T2 and N1 stage, incomplete initial surgery, treatment before 1995, and European cooperative group treatment. Patients with gross residual disease after initial incomplete resection/biopsy had similar outcomes in both continental groups. The better global survival of patients treated in American studies was accounted for by differences in outcome in the subset of those with grossly resected tumors (OS 86% [se 3] for COG patients vs. 68% [se 4] for European patients (P = 0.004)). When excluding chemotherapy duration from the model, analysis in this subset of patients showed that cooperative group (P = 0.001), site (P = 0.001), and T stage (P = 0.05) were all significant. However, after adding duration of chemotherapy (≥27 weeks) to the model, only primary site remained significant (P = 0.006).

Conclusion

This meta‐analysis confirms the role of many established prognostic factors but identifies for the first time that chemotherapy duration may have an impact on outcome in patients with grossly resected tumors. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.