Autologous Transplantation in Hodgkin Lymphoma in Uruguay: A Country Perspective
Authors: Oliver Ana Carolina , Spinelli Virginia Lema , Ambrosoni Carla , Figueroa Byron , Moro Maria Isabel , Borelli Gabriel , Irigoin Victoria , Rocca Alejandra , Ferrando Martin , Galeano Sebastian , De Giuda Rosanna , Pierri Silvia , Martinez Caludia , Riva Eloisa , Gabus Raul Hector , Diaz Lilian , Muxi Pablo , Landoni Ana Ines 
Published: December 2024

Introduction: Hodgkin's lymphoma (HL) represents 10% of adult lymphomas. With ABVD as first-line treatment, a complete remission (CR) rate close to 80% is achieved. Refractory or relapsed patients receive salvage chemotherapy (CT) and consolidation with autologous transplant (Auto-SCT) if they are fit. It is well known that the greatest benefit of Auto-SCT in terms of Overall Survival (OS) is observed in patients who achieve metabolic CR (CMR) prior to it. There are 3 adult transplant centers (SMI-CITMO, Hospital Británico and Hospital Maciel) in Uruguay, so the aim of this report covers the results of salvage chemotherapy and autologous transplantation throughout the country.
Methods: retrospective study of consecutive HL patients.
Results: Between 01/07-12/22, 163 HL's patients received an auto-HSCT. Median age at SCT: 33 years old (15-65). Sex: female 73 (45%). Nodular sclerosis HL was the most frequent subtype: 75,5%. Stage: III-IV: 51%. B symptoms: 23.3%.
First line: ABVD 158 (96.9%). Second-line: Platinum-based: 75% and Gemcitabine-based: 13%. Median number previous treatments: 2 (1-5). Two patients received Pembrolizumab and 5 Brentuximab vedotin before transplant.
Response before Auto-SCT: CR: 33.5%, PR: 52.5%, SD: 2,4%, progression: 11.6%. 87 (53.4%) were evaluated with PET. This is in part because end of treatment PET was available to everyone since 2012. Of the CR patients, 68% were assessed by PET and 43% of the PR. Conditioning regimen: BEAM: 77.3%, BEAC: 9.2%. Response to SCT: CR: 78%, PR: 5%, Progression: 9,2%.
79.8% had BV indication following current guidelines. The use of maintenance was performed in 11.7%, mostly regarding the availability of the drug in the country.
42 relapsed post-transplant (25.8%), 10 proceeded to allogeneic SCT. Median time to relapse: 11 months (0-55). Only 16.2% of patients in CMR pre SCT relapsed however, 40% of patients in PR or less by PET relapsed after transplant (p=0.017).
With a median follow up of 47.6 months (2.3-165.2), median OS has not been reached. The 4 years OS was 78%: in CR patients 89% and 73% in no CR (p=0.027). The 4 years PFS was 72%: in CR patients 82% vs 66% in no CR (p=0.078). The 4 years OS was 83% in patients transplanted after 2 lines vs 61% in more than 2 (p=0.002).
In the PET pre transplant cohort: 4 years OS in CMR patients was 97% vs 67% in no CMR (p=0.001). The 4 years PFS in CMR patients was 83% vs 57% in no CMR (p=0.017). There was no statistically difference in PFS in patients transplanted in CMR after 2 lines versus more than 2 (p=0,09).
It is important to highlight that patients transplanted in SD or progression had a 4 year-OS and PFS of 46% and 49%, suggesting that it is a reasonable treatment option in places where access to new drugs is difficult.
Discussion: Every Uruguayan has access to a transplant funded by Fondo Nacional de Recursos, which makes transplantation equitable and accessible. Although new drugs approvals are limited, the access is increasing over the years. This is the first report of our country as a whole on the results of transplant in Hodgkin's lymphoma, which makes these results of great local, regional and applicable value for countries with similar limitations. CR after second line was 33.5% similar to international reports. Only 7 patients accessed novel drugs pre transplant. Access to pre SCT PET was 54.3%. The 4 years OS was 78% and PFS was 72%. We observed a difference in OS in patients transplanted in CR versus non CR however, no PFS difference was proved. Looking into the PET's pre transplant cohort, there was a difference in OS and PFS at 4 years in patients transplanted in CMR versus non CMR: 97% vs 67% and 83% vs 57%, respectively. These results highlight the value of a widely available study as PET on long-term patient outcomes.
Approximately 57% of patients transplanted in PR or less by PET are cured, transplant continues to be a really important tool in general, specially in those countries with limited resources. Patients transplanted in stable disease or in progression could also be progression free 49% at 4 years, and they could even be cured.
Conclusions: our results reflects that CMR pre SCT has an impact to achieve better outcomes. Accessing second-line treatments that allow for deeper remissions is one of our current challenges. Auto-SCT remains the standard of care in fit patients as salvage therapy in HL, even in those patients who do not achieve CMR and it's not possible to access new drugs, almost half of the patients could be cured.