Ifosfamide,gemcitabine, and vinorelbine is an effective salvage regimen with excellent stem cell mobilization in relapsed or refractory pediatric Hodgkin lymphoma

We describe 12 pediatric patients (8‐16 years) with primary refractory (N = 6) or first relapse (N = 6) Hodgkin lymphoma (HL) treated with ifosfamide, gemcitabine, and vinorelbine (IGEV). The overall response rate to IGEV was 100%, with seven (58%) complete responses (CR) and five (42%) partial responses. Successful CD34⁺ stem cell mobilization was achieved in all patients. Following subsequent autologous stem cell transplantation, 10 patients (83%) achieved CR. At a median follow‐up of 71 months, 11 patients had no evidence of disease. Five‐year second event‐free survival and overall survival were 83% ± 11.0% and 90.0% ± 9.5%, respectively. IGEV is an effective salvage regimen for children with relapsed/refractory HL.     

Comparison of treatment outcomes of childhood Hodgkin lymphoma in two US centers and a center in Recife, Brazil

BACKGROUND: Pediatric Hodgkin lymphoma (HL) has a cure rate of more than 80% in high-income countries (HIC). However, more than 80% of the world's children live in low-income countries (LIC), where the cure rate is often much lower. PROCEDURE: We compared the outcome of HL of 371 patients treated at two pediatric oncology centers in the US to that of 62 patients treated at one center in Recife, Brazil (IMIP) to determine whether the same treatment strategy should be used in both high-income and LIC. The logrank test was used to compare event-free and overall survival. RESULTS: The percentages of patients with unfavorable disease at each center were similar (P = 0.72). Patients with favorable disease at IMIP had estimated 5-year survival rates comparable to those of the US centers (100% and 99%, respectively). Among patients with unfavorable disease, those treated at IMIP had a 5-year event-free survival (EFS) rate of 60%, compared to 78% at the US centers; (P = 0.08). The 5-year survival estimate after relapse was 25% at IMIP versus 61% at the US centers (P = 0.08). The 5-year overall survival for patients with unfavorable disease was 72% at IMIP versus 90% at the US centers (P = 0.01). CONCLUSIONS: Intensive frontline therapy should be considered for patients with unfavorable HL in LIC where the relapse rate is high and the salvage rate is low, provided that supportive care is adequate.     

Pretransplant functional imaging and outcome in pediatric patients with relapsed/refractory Hodgkin lymphoma undergoing autologous transplantation

1 Background

Pretransplant functional imaging (FI), particularly a negative positron emission tomography (PET), is a strong predictor of outcome in adults with relapsed or refractory Hodgkin lymphoma (HL), but data in pediatrics are limited.

2 Methods

The medical records of 49 consecutive pediatric patients, who received autologous transplant at a single institution, were retrospectively analyzed. All patients had either gallium or PET scan before transplant and were conditioned with carmustine, etoposide, cytarabine, and melphalan (BEAM). Deauville scores were retrospectively assigned for patients with PET (score ≥ 4 positive).

3 Results

Of the 49 patients (median age, 16.2 years), 41 (84%) were pretransplant FI negative and eight (16%) were pretransplant FI positive, after first‐ to fourth‐line salvage therapy, and a median of two salvage cycles. Eighteen patients (37%) received posttransplant radiation. At a median follow up of 46 months, 45 patients (92%) were alive and disease free, and there were three nonrelapse deaths and only one relapse death (Deauville score of 5). The 4‐year progression‐free survival (PFS) for the entire cohort was 92% (95% confidence interval [CI]: 78–97), and PFS based on pretransplant disease status was 95% (95% CI: 82–99%) in the negative FI group versus 75% (95% CI: 31–93) if positive FI (P = 0.057).

4 Conclusion

Our analysis revealed outstanding outcomes for children and adolescents with relapsed/refractory HL. There were too few relapses to identify the predictive value of pretransplant metabolic status, but pediatric patients with relapsed/refractory HL and a negative pretransplant FI had excellent survival.     

A role for surgery in the treatment of relapsed Hodgkin lymphoma

Treatment of Hodgkin lymphoma (HL) has advanced over time, rendering a fatal disease now largely curable. Multiagent chemotherapy regimens, hematopoietic stem cell transplantation, and radiotherapy are the mainstays of care. Surgical intervention is rarely indicated other than for biopsy at diagnosis. However, for patients with recurrent relapsed HL isolated to one anatomical location, refractory to all other therapy, there may be a beneficial role for surgical excision. Herein, we report the surgical management of three relapsed patients with stage IVB HL who were refractory to multiple other therapeutic approaches, who all achieved good event‐free survival after operative management.     

Hodgkin lymphoma in a child with sickle cell anemia

There are reports of patients with sickle cell disease who developed hematological malignancies but the relationship between these malignancies and sickle cell disease (SCD) is not yet defined. The co-existence of a hematological malignancy with SCD poses certain challenges for the management of each condition. We describe a 7-year-old boy with sickle cell anemia who developed Hodgkin's lymphoma and the challenges of management. He presented with a 4-year history of bilateral neck swelling and a 2-month history of weight loss and high-grade fever. Histology of a lymph node biopsy was consistent with mixed cellularity Hodgkin's lymphoma. He was treated with five cycles of Cyclophosphamide, Vincristine, Procarbazine and Prednisolone (COPP) and had complete clinical response. Chemotherapy was associated with an increase in frequency of painful crises and complicated by septicaemia. Blood transfusion needs were minimal; apart from the transfusion preceding the first cycle of chemotherapy, there was no need for further transfusion. Myelosuppression was not a problem in the patient; he responded well to antibiotics during the two episodes of septicemia without the use of hemopoetic growth factor. Patients with sickle cell anaemia who develop Hodgkin's lymphoma can be successfully treated with chemotherapy along with supportive management for crises and infections.     

Differentiation between rebound thymic hyperplasia and thymic relapse after chemotherapy in pediatric Hodgkin lymphoma

Background

Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification. The aim of this study was to identify parameters that differentiate between RTH and thymic LR in the anterior mediastinum.

Methods

After completion of CTX, we analyzed computed tomographies (CTs) and magnetic resonance images (MRIs) of 291 patients with classical Hodgkin lymphoma (CHL) and adequate imaging available from the European Network for Pediatric Hodgkin lymphoma C1 trial. In all patients with biopsy-proven LR, an additional fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT was assessed. Structure and morphologic configuration in addition to calcifications and presence of multiple masses in the thymic region and signs of extrathymic LR were evaluated.

Results

After CTX, a significant volume increase of new or growing masses in the thymic space occurred in 133 of 291 patients. Without biopsy, only 98 patients could be identified as RTH or LR. No single finding related to thymic regrowth allowed differentiation between RTH and LR. However, the vast majority of cases with thymic LR presented with additional increasing tumor masses (33/34). All RTH patients (64/64) presented with isolated thymic growth.

Conclusion

Isolated thymic LR is very uncommon. CHL relapse should be suspected when increasing tumor masses are present in distant sites outside of the thymic area. Conversely, if regrowth of lymphoma in other sites can be excluded, isolated thymic mass after CTX likely represents RTH.     

Temozolomide in resistant or relapsed pediatric solid tumors

PURPOSE: We report the off-label study aimed at investigating the use of temozolomide (TMZ) as single agent in relapsed or resistant pediatric solid tumors. The drug was administered at the dose of 215 mg/m2/day x 5 days or 180 mg/m2/day x 5 days in patients with prior craniospinal irradiation (CSI) or autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Fifty two patients, median age 127.6 months, with resistant or relapsed solid tumors were enrolled. Tumor types were: neuroblastoma (NB; n = 17), medulloblastoma (MB; 8), brain stem glioma (BSG; 8), extraosseous Ewing's sarcoma/peripheral neuroectodermal tumor (EOES; 4), Ewing's sarcoma (ES; 4), anaplastic astrocytoma (AA; 3), rhabdomyosarcoma (RMS; 2), ependymoma (EP; 2), cerebral primitive neuroectodermal tumor (cPNET; 2), hepatocarcinoma (HC; 1), and osteosarcoma (OS; 1). All patients were pre-treated. Two outpatient courses were administered, with a median of 4.8 courses/pt. RESULTS: Objective response-rate (CR + PR + MR) in our series was 13.4% (1.9% CR, 3.8% PR, and 7.7% MR), SD occurred in 38.4% of patients and 48% had PD. The median survival was 7.8 months (range 1-37) and median time to progression was 3.4 months (range 1-20); these data were significantly correlated with histology and previous nitrosureas administration in multivariate analysis. Haematological toxicity grade 3-4 (mainly thrombocytopenia) was observed in 21.4% of administered courses, nausea was reported in 3.1% and respiratory distress in 0.7%. CONCLUSION: Oral TMZ was well tolerated in children with resistant or relapsed solid tumors and showed activity in NB and CNS tumours refractory to standard chemotherapy.     

Gemcitabine and vinorelbine as a salvage regimen for relapse in Hodgkin lymphoma after autologous hematopoietic stem cell transplantation

The authors describe two consecutive pediatric patients with relapsed Hodgkin lymphoma after autologous hematopoietic stem cell transplantation who had objective responses with a novel combination of gemcitabine and vinorelbine. This novel and promising combination needs to be studied in a larger number of relapsed Hodgkin disease patients.