Prospective Collaborative Study for Relapsed / Refractory Hodgkin Lymphoma
● Principal Investigator: Dr. Amita Mahajan
● To study prospectively the clinical course and outcome of patients with Relapsed and Refractory Hodgkin Lymphoma using a risk stratified, response-based approach
● To determine factors that predict response following salvage chemotherapy
● Patients < 21 years with Relapsed HL: Disease detection & 3 months after completion of therapy.
● Or Refractory HL: Persistent disease that has failed to achieve complete remission on frontline therapy or progression at any point during therapy. Treated upfront with ABVD/ non-ABVD strategy, with or without radiotherapy.
● Interim Response to Salvage Chemotherapy after two cycles of Gem cite-Vinorelbine.
● Event free survival and Overall Survival for all patients treated as per this risk-stratified, response-based algorithm.
The current treatment outcomes of Hodgkin Lymphoma (HL) with combined modality therapy are excellent with treatment failure expected in only about 10% of patients with limited disease. The success rates of advanced stage HL have also improved but a proportion will not achieve complete remission and 20-30% of responding patients will subsequently relapse.
The excellent response to frontline therapy among children and adolescents with HL limits opportunities to evaluate second-line or salvage therapy. Because of the small number of patients that fail primary therapy, no uniform second-line treatment strategy exists for this patient population. In most centres across developed countries, salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed/ refractory HL. The authors of two randomised phase 3 clinical trials in adults showed improved progression free survival (PFS) in patients undergoing high dose chemotherapy and ASCT compared with patients treated with salvage chemotherapy and radiotherapy, although there was no increase in Overall Survival (OS). These trials form the basis for the management of patients with relapsed or refractory HL. However, it is increasingly being recognized that not all patients need high dose chemotherapy and ASCT to achieve long term cure. Children with localised, favourable (relapse ≥12 months after completing therapy) disease recurrence whose original therapy involved reduced cycles of risk-adapted therapy or with chemotherapy alone have a high likelihood of achieving long-term survival after treatment with more intensive conventional chemotherapy and low-dose involved field radiation therapy
This issue is of greater significance in our scenario because a significant proportion of patients may have received sub-optimal therapy upfront due to suboptimal dosing, reduced dose intensity, no assessment of early response, persistence with the same regimen despite inadequate response, omission of RT in front line therapy even when indicated due to poor access. Furthermore, not all patients have access to High Dose Chemotherapy and ASCT. The significant response rates even after relapse warrant treatment for these patients even in resource limited settings.
In the current study, we propose a risk-stratified, response-based approach for this cohort based on a critical appraisal of published outcomes following retreatment with chemotherapy with and without ASCT, with incorporation of the prognostic factors that are known to influence outcome.