PET/CT Response Assessment in Pediatric Hodgkin Lymphoma: Does Deauville Score 3 Reflect Negativity?

BACKGROUND: FDG PET is required for the staging and response evaluation of pediatric Hodgkin lymphoma. This study aimed to evaluate the outcomes of pediatric patients with Hodgkin's lymphoma based on interim PET CT assessments of early response following second-cycle chemotherapy using the Deauville score (DS). It also determines whether DS-3 is providing an adequate or inadequate response. METHODS: We conducted a retrospective cohort study including 504 pediatric patients with classic Hodgkin lymphoma who were treated with chemotherapy based on the Euro-Net protocol at the Children Cancer Hospital Egypt from March 2019 till the end of October 2022. RESULTS: Patients with adequate response DS 1/2 and DS 3 showed nearly the same 3-year event-free survival (EFS) of 91.9% and 91.5%, respectively, compared with those patients with inadequate response DS 4/5, who showed an EFS of 80.4% (P=0.001). Patients with a DS 3 at interim PET evaluation were considered negative as DS 1/2. Patients of DS 3 group who did not receive radiotherapy had a much worse 3-year EFS by the existence of positive B symptoms, an ESR>30, or an advanced stage. Radiation therapy did not improve the 3-year EFS in patients with an inadequate response (DS4/5) and poor prognostic characteristics. They still need more advanced treatment. CONCLUSION: DS 1/2 and DS 3 had about the same 3-year EFS, which is better than the 3-year EFS of patients with DS 4/5. Therefore, we can classify DS 3 as having negative FDG PET CT uptake.

Acute promyelocytic leukemia in children cancer hospital Egypt.

BACKGROUND: Pediatric acute promyelocytic leukemia (APL) accounts for 5 to 15% of all myelocytic leukemia. A retrospective analysis of pediatric patients diagnosed and treated with APL was conducted at CCHE from July 2012 to the end of December 2019, to report the prevalence, clinical characteristics, results, and risk factors associated with induction failure and early death. RESULT: Sixty-two patients were reported, with an age greater than ten, an initial poor coagulation profile, and a total leukocyte count (TLC) greater than 30 103/mm3 influencing 5-year overall (OS) and event-free survival (EFS), as well as a high promyelocyte count affecting 5-year EFS. Patients received a regimen based on the COG AAML0631 protocol. High-risk patients with an initial TLC > 10 × 103/mm3 and an initial promyelocytic count of 30% or more with a substantial P-value are prognostic markers for early death during induction. In females, wild FLT3 increases the risk of differentiation syndrome (DS). Receiving steroids with all-trans retinoic acid (ATRA) induction may reduce the occurrence of DS. Relapse alters the outcome. In the current study, 45 patients are alive in complete remission, with a 5-year OS of 72.5% and a 5-year EFS of 69.4%, respectively. CONCLUSION: Pediatric APL outcomes are influenced by age above 10, an initial poor coagulation profile, and a promyelocyte count of more than 10%. An initial leukocyte count of more than 10 × 103/mm and an initial promyelocytic count of more than 30% increase the risk of early death. Receiving steroids with ATRA may reduce the occurrence of DS.

Patterns and Outcomes of Acute Central Nervous System Complications During Treatment of Childhood Acute Lymphoblastic Leukemia: A Single-center Experience.

Central nervous system (CNS) complications are considered adverse events during the treatment of pediatric acute lymphoblastic leukemia (ALL). This study aimed to assess the incidence, types, clinical and radiologic patterns, risk factors, and the fate of different CNS complications during the treatment of pediatric ALL. A retrospective study included 390 patients with pediatric ALL, treated according to St. Jude total XV protocol at the National Cancer Institute, Cairo University, from January 2012 to December 2017. Thirty-nine (10%) patients developed different types of CNS complications. Nineteen (4.9%) patients had cerebrovascular complications, 12 (3.1%) patients had posterior reversible encephalopathy syndrome (PRES), and 6 (1.5%) patients had leukoencephalopathy; both CNS infections and leukemic infiltrates were diagnosed in one patient each. CNS complications were significantly higher in patients older than 10 years old, patients with high-risk disease, and patients who were classified as CNS III status with a statistically significant P value of 0.040, 0.020, and 0.002, respectively. There were 31 (79.5%) cases that achieved complete recovery, 6 (15.4%) patients who died, and 2 (5.1%) patients who developed residual neurological deficits. In conclusion, pediatric patients with ALL, who presented with older age, high-risk disease initially, and had initial CNS III status, were at higher risk of developing acute CNS complications during their treatment period. Patients who developed visual disturbances were associated with unfavorable outcomes. Despite that, around 80% of patients showed complete recovery, but still, 15% of them died from these complications.

Prognostic Factors and Treatment Outcome of Relapsing and Refractory Pediatric Mature B-cell Non-Hodgkin Lymphoma, Children's Cancer Hospital Egypt Experience.

BACKGROUND: Relapsed non-Hodgkin lymphoma treated by chemotherapy and hematopoietic stem cell transplantation (HSCT) has a dismal prognosis. PATIENTS: It is a retrospective study, including pediatric patients diagnosed as mature B-cell non-Hodgkin lymphoma who were primarily refractory or relapsed over 8 years at CCHE. The aim of the study was to analyze the prognostic factors and outcomes of this group of patients. Our result is, 53 of 750 (7%) patients were included. Thirty-four (64.2%) patients had Burkitt lymphoma. Forty-eight (90.6%) patients received LMB 96 protocol initially. The median delay of duration between chemotherapy cycles in first-line treatment was 37 days. Thirty-five (66%) patients relapsed, 23 (65.7%) of them relapsed early, whereas 18 (34%) had tumor progression. Thirty-one (58.5%) patients presented with stage IV at the time of relapse. rituximab, ifosfamide, carboplatin, etoposide was the second line of treatment in 42 (79.24%) patients, and complete second remission was achieved only in 13 (24.3%) patients. Allogeneic HSCT was done for 4 (7.5%) patients, and auto HSCT was done for 3 (5.7%) patients. Three years of overall survival for relapsed and progressed patients were 35.3% and 11.1%, respectively, with a P-value of 0.009. Three years overall survival for patients who underwent HSCT was 85.7% compared with 18.1% for no HSCT with a P-value of 0.007. CONCLUSIONS: The relapse rate is higher than literatures because of the delay of duration between chemotherapy cycles in first-line treatment and more advanced stage at time of relapse. Progression of the disease had a worse outcome than relapse. HSCT in patients with the second remission markedly improved the outcome.

Can FDG-PET replace biopsy for the evaluation of residual tumor in pediatric mature B-cell non-Hodgkin lymphoma?

INTRODUCTION: The aim of our study is to evaluate the role of 18 F-labeled fluorodeoxy glucose positron emission tomography (18 FDG-PET) scan for the detection of viable residual mass in pediatric mature B-cell non-Hodgkin lymphoma (NHL). This study also aims to detect the negative predictive value, positive predictive value (PPV), sensitivity, and specificity of 18 FDG-PET. PATIENTS AND METHODS: A retrospective, cross-sectional nonrandomized study was carried out. We included all patients with newly diagnosed mature B-cell NHL treated at the Children Cancer Hospital Egypt during the period between July 2007 and the end of May 2018. Patients were included in the study if they (a) had a residual tumor mass, (b) underwent an 18 FDG-PET scan, and (c) had a pathologic documentation of this residual tumor. Patients were followed up till June 2019. RESULTS: Thirty-six patients were included, for whom 39 biopsies were performed. Mean age was 7.7 years. Median follow-up period was 52.8, range 6.1 to 117 months.18 FDG-PET scan was positive (Deauville score 3, 4, or 5) in 24 of 39 patients (61.5%), while it was negative (Deauville score 1 or 2) in 15 patients (38.5%). Positive 18 FDG-PET scan and biopsy were performed in 15 of 39 samples (38.4%; true positive, TP), while they were both negative in 13 samples (33.3%; true negative). Nine patients (23%) had positive scan and a negative biopsy (false positive), while 2 patients had negative uptake and a positive biopsy (false negative, FN)). Sensitivity of the 18 FDG-PET scan was 88.2% and specificity was 59.1%. PPV was 62.5% and NPPV was 86.6%. CONCLUSION: Changing therapy on the basis of a positive finding alone at the time of evaluation is not recommended. FN results exist, so biopsy confirmation is required to avoid the missing refractory disease. If negative, 18 FDG- PET can replace a biopsy if the latter is inaccessible or carries an unnecessary risk.

Outcome of Childhood Acute Myeloid Leukemia With FLT3-ITD Mutation: The Experience of Children's Cancer Hospital Egypt, 2007-17.

INTRODUCTION: The presence of FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutation in pediatric acute myeloid leukemia (AML) is associated with high rates of induction failure and worse survival. Its presence places the patient into a high-risk group. We aimed to describe the outcome of pediatric AML with FLT3-ITD mutation. PATIENTS AND METHODS: We performed a retrospective analysis of cases of AML from July 2007 till July 2017 at Children's Cancer Hospital Egypt. RESULTS: Seventy-one patients had FLT3 gene mutation out of 687 patients with AML. Sixty-five patients had FLT3 gene mutation with allelic ratio > 0.4; 43 (66.1%) of 65 patients experienced complete remission (CR). Of the 43 patients, 16 patients maintained CR, 18 patients relapsed after first CR, 8 patients died, and 1 patient was lost to follow-up. Patients with relapsing disease died after salvage chemotherapy, except for one patient, who was alive after second CR. Allogeneic bone marrow transplantation (allo-BMT) was performed for 9 (13.8%) of 65 patients in first CR, of whom 8 were alive and in CR, and 1 patient experienced disease relapse and died. Seven patients (10.7%) were alive without allo-BMT. Three years' overall and event-free survival for patients with FLT3-ITD mutation with high allelic ratio was 26.9% and 22.8%, respectively. Three years' overall and event-free survival for patients treated with allo-BMT was 77.8% and 78.8%, respectively, versus patients treated without allo-BMT, 16.3% and 12.8%, respectively. CONCLUSION: FLT3-ITD mutation in pediatric AML was associated with poor treatment outcomes, and the survival of relapsing patients was extremely poor. Allo-BMT in first remission was the best treatment option. Alternative donor transplants and FLT3 inhibitors are needed to improve outcome in developing countries.

Prognostic Factors and Treatment Outcome of Pediatric Anaplastic Large Cell Lymphoma Treated at the Children Cancer Hospital Egypt.

INTRODUCTION: The aim of the current study is to report the epidemiologic data, response rate, treatment outcome, and overall survival of anaplastic large cell lymphoma (ALCL) patients during the 8-year period. PATIENTS AND METHODS: A retrospective study included all patients with newly diagnosed ALCL from July 2007 till December 2015. RESULTS: A total of 48 patients were enrolled. The majority (66.7%) were male individuals. Twenty-one patients (43.7%) were low stage I or II, whereas 27 (56.2%) had advanced stage III or IV. Two patients (4.2%) died during induction chemotherapy. Disease status at last follow-up showed 35 patients (72.9%) in complete remission, 5 (10.5%) relapse, and 5 disease progression. The median time to relapse was 17.2 months. Four patients (8.4%) were salvaged by high-dose chemotherapy ifosphamide, carboplatine, etoposide followed by autologous hematopoietic stem cell transplantation, whereas 5 (10.5%) died out of disease progression. The 5-year overall survival and event-free survival were 81.2% and 68.6%, respectively. Median FU period was 58.7 month. Multivariate analysis included age, sex, stage, and response to chemotherapy and showed no statistical significance. CONCLUSION: Treatment of ALCL according to the Children's Oncology Group ANHL 0131 protocol is well tolerated. The relapsing patient could be salvaged by high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

Surgery in perforated pediatric intestinal lymphoma.

BACKGROUND: Perforation is the most common surgical complication in pediatric intestinal lymphoma. During operation, many surgical decisions are debatable. AIM: To assess the outcome of surgical management of perforated pediatric intestinal lymphoma. PATIENTS AND METHODS: This is a retrospective analysis of all pediatric patients (<18 years old) with intestinal lymphoma treated in our hospital between July 2007 and June 2017. Risk factors for perforation, type of management and outcome in cases of intestinal perforation were analyzed. RESULTS: The study included 240 patients with intestinal lymphoma. Perforation developed in 16 patients (6.7%) with a median age of 5.3 (range: 2.8-15.7) years. Most of the patients (92.5%) had Burkitt lymphoma. The ileum was the most common site of perforation (n = 10). Perforation occurred at presentation (n = 2), during induction (n = 10), during maintenance chemotherapy (n = 2), or at relapse (n = 2). Primary resection anastomosis was done in 12 patients. The resected specimen showed a viable tumor in ten patients. Wound infection (25%) and dehiscence (12.5%) were the most common postoperative complications. The 5-year overall and event-free survivals of patients with perforation were 78.6% and 71.4%, respectively, compared with 85.5% and 81.2% in non-perforated patients; the difference was not significant (p = 0.374 and p = 0.270, respectively). CONCLUSION: Perforation is not an adverse prognostic factor for survival in pediatric intestinal lymphoma patients. Primary resection anastomosis seems to be a safe option if complete tumor resection is feasible.