Pediatric hodgkin lymphoma: Making progress

Hodgkin lymphoma (HL) is one of the more common cancers encountered among pediatric and adolescent patients; however, most HL occurs in adults, and children constitute only a small proportion of the total number of cases. Treatment outcomes for pediatric HL are excellent and current strategies focus on reduction of therapy-related toxicity while maintaining high survival. This has been achieved by identifying patient cohorts who are at a lower risk for relapse and can be successfully treated with reduced amounts of chemotherapeutic agents and radiation therapy. This identification has been assisted by better understanding of newer imaging modalities, in particular functional FDG–PET imaging. Patients who fail first-line therapy continue to have a chance of cure, and a variety of modalities are available for their treatment. New therapeutic agents, both traditional and biological, are under assessment

Incidence, clinical distribution, and patient characteristics of childhood cancer in Saudi Arabia: A population-based analysis

Purpose: Information regarding the incidence and patterns of childhood malignancies is disproportionately overrepresented by high-income countries, representing mainly the Caucasian population. There is a need to evaluate and disseminate information for other ethnicities, particularly from the Middle East.Methods: Data from the National Cancer Registry, Saudi Arabia (SA-NCR), for pediatric patients (age 0-14 years) diagnosed between 2005 and 2009 and for similar patients at our institution during the same period were analyzed. Population numbers reported in the 2007 national census were used to calculate the annual incidence of childhood cancer.Results: Data from SA-NCR on 3885 patients were included in this analysis. The median age was 5.58 years, and 57.3% were males. The annual age-specific cancer incidence rate (ASR) for children in SA is 99.83 per million population; ASR per million for lymphoid leukemia is 25.75, 12.05 for brain tumors, and 9.82 for Hodgkin lymphoma. Of all childhood cancers in SA, 35% were treated at our institution. The five-year overall survival for these 1350 patients is 74.6% (median follow-up 7.52 years [95% confidence interval: 7.36-7.68]). Significant differences in the distribution of childhood malignancy subtypes were evident compared with other countries.Conclusion: We have reported differences in the cancer ASR and cancer subtype distribution for children in SA as compared with the worldwide incidence and with other populations. This paper provides a comprehensive epidemiological overview of childhood cancer in SA, which could be extrapolated to other regional Arab populations

Outcome Of hematopoietic cell transplantation (HCT) In pediatric patients with Hodgkin lymphoma (HL): Single institution results from Saudi Arabia

Most pediatric patients with Hodgkin lymphoma are cured of their disease with standard combined-modality first-line therapy. Those who relapse are subjected to salvage chemo-radiotherapy, and patients who respond often undergo either autologous or allogeneic HCT, with a reported outcome ranging from 40%-60%. Variables affecting the outcome of such patients are not clearly defined. This study retrospectively reviewed the clinical characteristics and outcome of patients who underwent HCT at our institution. Between 1995 and 2012, 29 pediatric (age \u3c14 years) patients with HL underwent HCT. This cohort included 24 boys and 5 girls. Their median ages at initial diagnosis and at HCT were 9.85 years (mean 8.85; range 3.6-13.75) and 12.18 years (mean 11.24; range 5.6-14.9), respectively. 28 patients had classic HL (23 nodular sclerosis, 3 mixed cellularity, 1 lymphocyte-depleted, and 1 lymphocyte-rich) and one patient had nodular lymphocyte-predominance HL. Ten had persistent/progressive disease following first line therapy, while 19 had relapsed following achievement of complete response (CR). For these patients median time to relapse from completion of first-line therapy was 16.9 months (mean 20.1; range 1.9-53.1). All patients received salvage chemotherapy and/or radiotherapy prior to HCT; fifteen patients achieved CR, 13 had a partial response and one had progressive disease. Two patients had allogeneic bone marrow (BM) grafts from matched-related donors, while the rest had autologous grafts (16 BM; 10 PBSC; 1 BM+PBSC) following chemotherapy-based myeloablative conditioning. Twelve patients have relapsed/progressed post-HCT at a median of 6.04 months (mean 11.8; range 1.02-71.4). Nine patients have died; eight because of disease progression and one due to sepsis post HCT. Only two patients died within the first 100 days post HCT, giving a Day-100 mortality rate of 6.8%. Two patients who relapsed after HCT were salvaged with chemo/radiotherapy and remain disease free 2.8 and 9.7 years later. The 5-year estimated overall survival (OS) from HCT for the whole cohort is 61.6%, with an event free survival (EFS) of 57.9%. Patients who had persistent/progressive disease at the end first-line therapy or relapsed \u3c6months off therapy had a worse OS and EFS as compared to those who relapsed later (OS 42.9% v. 75.3%, p=0.047 [Taron-Ware]; EFS 41.7% v. 60.8%, p=0.052 [Taron-Ware]). The outcome of patients with relapsed/refractory HL following HCT is encouraging, as a majority of patients survive free of their lymphoma. Timing of relapse/progression remains an important prognostic factor and patients who fail early may be considered for novel therapeutic approaches

Outcome Of hematopoietic cell transplantation (HCT) in pediatric patients with non-Hodgkin lymphoma (NHL): Single institution results from Saudi Arabia

Although HCT is an accepted component of the treatment strategy for relapsed/refractory pediatric NHL, only few studies have reported on the outcome for these patients. Most have reported on small numbers of patients, with survivals ranging from 27% to 75%. Clinical data were retrospectively retrieved for patients with NHL who had undergone HCT. Pre-HCT information, including pathologic diagnosis, response to first- and second-line therapy and pre-HCT disease status were collected, in addition to details of the transplant process and patient and disease outcome. Between 1996 and 2012, 28 pediatric patients with NHL underwent HCT. Primary diagnosis for these patients included Burkitt lymphoma (n=13), Large B-cell lymphoma (n=4), T-Lymphoblastic lymphoma (n=4), NK/T cell lymphoma/leukemia (n=3), Peripheral T-cell lymphoma (n=2), B-lymphoblastic lymphoma ((n=1) and anaplastic large cell lymphoma (n=1). The median age at HCT was 7.65 years (mean 8.2; range 1-14.3). Twenty had suffered a relapse of their disease, while five had primary progression; three patients with NK/T lymphomas underwent HCT as part of their first-line therapy. Fourteen patients had autologous (autoHCT) and 14 had allogeneic HCT (alloHCT). Among alloHCT, 11 had matched-related grafts while 3 had unrelated umbilical cord blood (UCB) grafts. At the time of HCT, 23 patients were in CR (CR1=7, CR2=15, CR3=1), and 5 had partial responses. HCT conditioning was myeloablative for all patients; in 18 patients, it was TBI-based. Fourteen patients suffered recurrence of their lymphoma post HCT at a median of 1.17 months from HCT (mean 6.2; range 0.63-42); 4 died in CR due to transplant-related toxicity, of these 3 were post alloHCT and one post autoHCT. Three patients have developed secondary malignancies (SMN; 2 post alloHCT and 1 post autoHCT). 10 patients were alive at last follow-up, all of whom were in CR. The 5-year estimated OS from SCT is 38.7%, with and EFS of 26%. There was no difference in 5-year OS or EFS among patients who received alloHCT v. autoHCT (OS 28.6% v. 49%; p=0.53, EFS 14.3% v. 37.5%; p=0.25) and among patients who did or did not receive TBI (OS 33.3% v. 48%; p=0.37, EFS 27.8% v. 18.8%; p=0.66). OS/EFS for patients with Burkitt lymphoma was 23.1%. Of the three patients with NK/T cell lymphoma two remain alive in CR 13.7 and 5.1 years after HCT. The outcome of relapsed/refractory non-Hodgkin lymphoma of childhood remains suboptimal. In addition to a high post-HCT relapse rate of 50%, HCT-related toxic mortality and SMN contribute to the poor outcome for this cohort of patients

Clinical characteristics and outcome of pediatric patients with stage IV Hodgkin lymphoma

Background and objectives: While treatment outcomes for patients with Hodgkin lymphoma (HL) have improved remarkably, patients with disseminated disease still have a poorer outcome. Stage IV HL is often reported with other \u27advanced stage\u27 categories, confusing the specific contribution of disease dissemination to the outcome. This single-institution report looks at characteristics and outcomes of this specific category.Patients and methods: The medical records of pediatric HL patients (\u3c 14 years) from 1975 through 2003 were retrospectively reviewed and the data analyzed.Results: Stage IV patients (n = 67) had more poor-risk characteristics than patients in stages I-III (n = 300) (B symptoms 86.6% vs. 19.3%, bulky disease 57.6% vs. 45.5% and mediastinal mass 77.6% vs. 29.7%; P \u3c .001 for all characteristics). The liver was the most common extralymphatic site (in 51.5% of patients with stage IV disease. Stage IV patients received chemotherapy (CT) alone (n = 55) or combined modality therapy (CMT) (n = 12). Fifty-four patients (80.6%) achieved complete remission, 2 (3%) partial remission, 10 (14.9%) had progressive disease and 1 was lost to follow up. Overall survival was 79.4% and event-free survival (EFS) was 63.9% at 5 years. There was a non-significant benefit for CMT (OS = 91.7% v. 77.1%, P = .3; EFS = 70.7% v. 62.7%, P = .3). Ten of 12 relapsed and only 1 of 10 progressive disease patients were salvaged. On multivariate analysis, failure to achieve complete remission with CT was associated with a poorer outcome.Conclusion: Stage IV disease is associated with poor risk features and confers a worse outcome than stage I-III disease. Achievement of complete remission with CT is an important prognostic feature. Slow responders may require novel and/or aggressive therapy to achieve complete remission

Loss to follow-up of patients with malignant lymphoma

Loss to follow-up (LTFU) in cancer patients is a serious problem, yet there is little data on this and on the underlying reasons. Of 144 paediatric and 431 adult patients with lymphoma diagnosed in 1997/1998 at King Faisal Specialist Hospital and Research Center, Riyadh (KFSHRC), 30% and 48.5%, respectively, were LTFU after 4 years (excluding patients known to have died). In 2001-2002, 196 paediatric and adult lymphoma patients at KFSHRC were enrolled in a prospective study in which explanations were obtained in detail for non-attendance at follow-up appointments (No Show). Sixteen months after commencement of the study, 49 patients were No Show, because of patient-based communication problems (20), transportation problems (8), patient not contactable (18), and personal reasons (3). In addition, patients were recorded incorrectly as No Show through hospital/patient communication problems. The No Show patients, especially the 23 who failed to keep a second appointment, are identifiable as potential LTFU during the 3 years in which this cohort will be followed. This study and, we suggest, other studies on LTFU should stimulate interest in this issue, in the predisposing factors, and in strategies to address them

Hodgkin lymphoma in very young children can be treated successfully without radiation therapy

Hodgkin Lymphoma (HL) is rarely seen in \u3c5-year olds in developed nations. Even in developing countries, where a tendency towards younger age of presentation has been shown, this represents a minority of cases. Little is known about the biology and behavior of these very young patients with HL as compared to older children.|Methods: We retrospectively reviewed HL cases diagnosed and treated at our institution between 1975 and 2003. HL was diagnosed histopathologically and staged clinically. The pediatric age group ranged from 0–14 years. Treatment strategy for these very young children was focused on the elimination of radiation therapy (XRT).Results: 69/368 (18.75%) patients were less than 5 years at diagnosis. When compared to older patients, there was a trend towards male predominance (M:F 4.31 v. 2.65; p=0.2), but no difference in the incidence of B-symptoms (26.1% v. 32.9%; p=1.0) and stage distribution (p=1.0). There was less mediastinal involvement (p=0.025) or bulky disease (p=0.01) in the younger patients. These patients had more mixed cellularity and less nodular sclerosis subtype (p=0.025). Fifty-five were treated with chemotherapy (CTX) alone, 12 with combined modality therapy (CMT) and 2 with XRT only. 35/55 CTX patients were treated with ABVD (20 per standard schedule, 13 modified and 2 unknown), 12 MOPP and 8 with hybrid or combination CTX (4 MOPP/ABVD, 3 COPP/ABVD and 1 unspecified). All CMT patients received ABVD (9 standard and 3 modified) and XRT (1500cGy/IF for 5, 1500cGy/EF for 4 and 2400cGy/EF, 2720cGy/IF and 3060cGy/IF for one each). The two XRT alone patients had stage I cervical disease and received 3900cGy and 3250cGy IFXRT. At ten years the EFS and OS for these patients under 5-years of age was 81.5% and 90.4%, respectively, compared to 75.5% and 90.5% for the children between 5 and 14 years of age (p\u3e0.5 for both comparisons). OS (86.4% v. 100%; p=0.3, Log Rank test) and EFS (81.0% v. 90.9%; p=0.4, Log Rank test) for CTX v. CMT groups were not statistically significantly different. The CTX group had more B-symptoms (29.1% v. 16.1%) and higher stage disease (stage III/IV 47.3% v. 25%; stage IV 12.73% v. 0%).Conclusions: HL patients \u3c5years old do not present with higher risk disease than older children. They can successfully be treated without XRT using CTX alone. XRT can be reserved for treating the few who relapse. This may result in reduction in XRT related toxicity, which can be significant in these very young children