Abstract
Autologous hematopoietic stem cell transplantation (auto-HCT) remains a cornerstone in relapsed Hodgkin lymphoma (HL), especially where access to novel agents is limited. We evaluated trends in outcomes after auto-HCT at King Hussein Cancer Center (KHCC) over two decades. We retrospectively analyzed adult HL patients who underwent auto-HCT between 2003 and 2020, divided into two eras: group A (2003–2015) and group B (2016–2020). Survival was estimated by Kaplan–Meier and compared by log-rank; prognostic factors were assessed with Cox regression. We identified 265 patients (group A: N = 149, 56%; group B: N = 116, 44%). The median age at transplant was 30.2 years (range 18.7–64). 109 (43%) had primary refractory disease.) With a median follow-up of 44 months (range 0.1-233.7), the 5-year OS and PFS were 64.4% and 46.7%, respectively. Compared to group A, patients in group B were more likely to receive ≥ 1 salvage regimen (54% vs. 40%, p = 0.027), receive GDP (gemcitabine, dexamethasone, cisplatin) (48% vs. 2.2%, p < 0.001), receive TEAM (thiotepa, etoposide, ara-C, melphalan) conditioning (20% vs. 6.5%, p < 0.001), and receive pembrolizumab at relapse (23% vs. 4.3%, p < 0.001), they were less likely to relapse post auto-HCT (35% vs. 55%, p = 0.003). Multivariate analysis identified younger age, CR at transplant, later transplant era, and longer remission duration after frontline therapy as independent predictors of improved survival (p = 0.01). Auto-HCT outcomes for HL at KHCC have improved significantly in the modern era. This reflects advances in salvage regimens, supportive care, reduced non-relapse mortality, and integration of immunotherapy for post-autoHCT relapses.
Keywords: Hodgkin lymphoma, Autologous stem cell transplantation, Salvage chemotherapy, Immune checkpoint inhibitors, Real-world outcomes, Low-and middle-income countries (LMIC)
Introduction
Over the past five decades, the treatment landscape for classical Hodgkin lymphoma (cHL) has undergone remarkable evolution. Initial improvements in cure rates were achieved through combination chemotherapy regimens such as MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) introduced in the 1970 s [1], which was later replaced by ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), that demonstrated superior efficacy and reduced toxicity, and has since become the standard of care [2, 3].
More recently, the integration of novel agents, including antibody-drug conjugates (ADCs) like brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) such as nivolumab and pembrolizumab, into both frontline and salvage settings has significantly improved outcomes, particularly for patients with advanced-stage disease [4–7]. Despite these advances, a subset of patients continues to experience relapse or refractory disease [8, 9], for these patients, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HCT) remains the cornerstone of salvage therapy, with durable remission achieved in approximately 50% of cases [10–13].
In Jordan, cHL accounts for approximately 39% of all lymphoma cases—a significantly higher proportion than reported in Western or Asian populations [14, 15]. The disease predominantly affects young adults and is mainly of the nodular sclerosis subtype, reflecting a unimodal age distribution that contrasts with the bimodal pattern observed in developed countries. Prior studies from Jordan have reported 3- and 5-year overall survival (OS) rates post-auto-HCT of 64.6% and 68.8%, respectively [16, 17].
However, despite the well-established role of auto-HCT in relapsed/refractory cHL, real-world data from low- and middle-income countries (LMICs) remain limited. This study evaluates two decades of experience in the management of relapsed/refractory cHL in a country with unique demographic profile and limited access to novel agents at King Hussein Cancer Center (KHCC), the country’s only comprehensive cancer center. to assess long-term survival trends and relapse patterns.
Methods
Study design and data collection
We conducted a retrospective cohort study of all adult patients (aged ≥ 18 years) with biopsy-proven classical HL (cHL) who underwent auto-HCT for relapsed or refractory cHL at KHCC between January 2003 and December 2020, patients with nodular-lymphocyte predominant HL or those who underwent auto-HCT outside KHCC were excluded. No formal sample-size calculation was performed because the study aimed to include the entire available consecutive cohort over the last 2 decades. There was no upper age limit for auto-HCT eligibility; patients were included based on clinical fitness, with ages ranging up to 64 years. Data were obtained from the institutional HCT registry and supplemented through review of electronic medical records. Extracted variables included demographic data, disease characteristics, prior therapies, transplant-related parameters, and post-transplant outcomes.
Definitions
Disease staging at diagnosis was classified according to the Ann Arbor staging system when available [18]. Treatment response was assessed using the Lugano 2014 criteria [19], incorporating PET-CT when available. Complete remission (CR) required Deauville score 1–3; partial remission (PR) was defined as Deauville 4–5 with reduced tumor burden Relapsed disease was defined as disease recurrence after CR to initial therapy, while refractory disease was defined as failure to achieve CR to frontline treatment or disease progression during or within 90 days of completing therapy (19,20). Overall survival (OS) was defined as the time from the date of auto-HCT to death from any cause or last follow-up. Progression-free survival (PFS) was defined as the time from auto-HCT to either disease progression or death from any cause, whichever occurred first. Non-relapse mortality (NRM) was defined as death without relapse/progression.
Statistical analysis
Patients were stratified into two cohorts based on the year of transplantation: Group A (2003–2015) and Group B (2016–2020), to allow for temporal trend analysis with balanced sample sizes. Continuous variables were summarized using medians and ranges, while categorical variables were reported as counts and percentages. Comparisons between groups were conducted using the chi-square test for categorical variables and the Mann–Whitney U test for continuous variables.
Time-to-event outcomes (OS and PFS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Univariable and multivariable Cox proportional hazards regression models were used to evaluate associations between covariates and survival outcomes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. Variables with a P value < 0.05 in univariable analysis were included in the multivariable model. All tests were two-sided, and P values < 0.05 were considered statistically significant. Statistical analyses were performed using SPSS version 25.0 (IBM Corp., Armonk, NY).
The study was approved by the Institutional Review Board (IRB) at KHCC (approval number 24 KHCC 82). Given the retrospective nature of the study, the requirement for informed consent was waived.
Results
Baseline characteristics
A total of 265 patients underwent auto-HCT for relapsed/refractory cHL between 2003 and 2020, including 149 patients in Group A (2003–2015) and 116 in Group B (2016–2020). The median age at transplant for the entire cohort was 30.2 years (IQR, 24.5–38.2), with the majority of patients younger than 40 years (80%, n = 212). Age distribution was similar across the two eras, as outlined in Table 1.
Table 1.
Baseline characteristics
| Variable | Group A (2003–2015) |
Group B (2016–2020) |
Total | p-value | ||||
|---|---|---|---|---|---|---|---|---|
| Age at Transplant, Median (IQR) | 29.5 (23.5–37.1) | 30.6 (25.4–38.7) | 30.2 (24.5–38.2) | 0.134 | ||||
|
Age < 50 Age > 50 |
140 (94.0) 9 (6.0) |
103 (88.8) 13 (11.2) |
243 (91.7) 22 (8.3) |
0.198 | ||||
|
Gender Female Male |
71 (47.7) 78 (52.3) |
64 (55.2) 52 (44.8) |
135 (50.9) 130 (49.1) |
0.275 | ||||
|
Received Radiotherapy Yes No |
83 (56.8) 63 (43.2) |
50 (43.5) 65 (56.5) |
133 (51.0) 128 (49.0) |
0.043 | ||||
|
Stage at Diagnosis Early (I-II) Advanced (III-IV) |
60 (43.2) 79 (56.8) |
38 (33.6) 75 (66.4) |
98 (38.9) 154 (61.1) |
0.157 | ||||
|
Smoking status Smoked Never/Ex-Smoker |
114 (78.6) 31 (21.4) |
95 (82.6) 20 (17.4) |
209 (80.4) 51 (19.6) |
0.518 | ||||
|
Extranodal Involvement Yes No |
46 (33.3) 92 (66.7) |
55 (49.1) 57 (50.9) |
101 (40.4) 149 (59.6) |
0.016 | ||||
|
Disease status Primary Refractory Relapsed |
56 (38.9) 88 (61.1) |
53 (47.7) 58 (52.3) |
109 (42.7) 146 (57.3) |
0.197 | ||||
| Time from Diagnosis to Salvage (months), Median (IQR) | 15.5 (11.2–30.8) | 15.5 (10.9–26.6) | 15.5 (11.1–28.7) | 0.502 | ||||
|
Time from Diagnosis to Salvage >12 months ≤12 months >12 months |
66 (44.3) 83 (55.7) |
47 (40.5) 69 (59.5) |
113 (42.6) 152 (57.4) |
0.623 | ||||
|
GDP used as salvage No Yes |
145 (98.0) 3 (2.0) |
62 (53.4) 54 (46.6) |
207 (78.4) 57 (21.6) |
< 0.001 | ||||
|
ICE used as salvage No Yes |
119 (80.4) 29 (19.6) |
92 (79.3) 24 (20.7) |
211 (79.9) 53 (20.1) |
0.948 | ||||
|
DHAP used as salvage No Yes |
51 (34.5) 97 (65.5) |
84 (72.4) 32 (27.6) |
84 (72.4) 32 (27.6) |
< 0.001 | ||||
|
Received pembrolizumab at relapse Yes No |
6 (7.4) 75 (92.6) |
28 (65.1) 15 (34.9) |
34 (27.4) 90 (72.6) |
< 0.001 | ||||
|
Received Allogeneic SCT Yes No |
16 (19.8) 65 (80.2) |
15 (34.9) 28 (65.1) |
31 (25.0) 93 (75.0) |
0.102 | ||||
| Follow up time from diagnosis, Median (IQR) | 53.1 (16.1 to 116.0) | 41.2 (23.9 to 60.4) | 44.6 (17.7 to 83.1) | 0.014 | ||||
| Follow up time from relapse, Median (IQR) | 22.4 (7.9 to 53.7) | 27.3 (11.6 to 45.8) | 24.3 (8.7 to 53.5) | 0.956 | ||||
| NRM | 13 (8.7) | 3 (2.6) | 16 (6.0) | 0.069 | ||||
GDP Gemcitabine, Dexamethasone, Cisplatin, ICE Ifosfamide, Carboplatin, Etoposide, DHAP Dexamethasone, High-dose Cytarabine (Ara-C), Cisplatin, NRM non-relpase mortality
At diagnosis, 61% (n = 162) of patients presented with advanced-stage disease (stage III–IV) and39% (n = 103) with early-stage disease (stage I–II), without significant variation between the two cohorts. Extranodal involvement was present in 40% overall, including bone marrow involvement in 20%. Group B had more frequent extranodal involvement vs. group A (49% vs. 33%; P = 0.016), bone marrow involvement occurred in approximately 20% of patients. Radiation therapy was administered to 135 (51%) patients, and this was less frequent in group B compared with group A (43% vs. 57%; P = 0.043).
The median time from diagnosis to salvage therapy was 15.5 months (IQR 11.1–28.7) and did not differ between the two groups. With respect to indication for transplant, 43% (n = 114) of patients were primary refractory to frontline therapy and 57% (n = 151) had relapsed disease. While the proportion of primary refractory cases was numerically higher in group B compared with group A (48% vs. 39%), this difference did not reach statistical significance (P = 0.197). When stratified by relapse timing, 57% (n = 151) of patients relapsed > 12 months after initial diagnosis, while 43% (n = 114) experienced an earlier relapse (≤ 12 months). Regarding salvage regimens, 55% (n = 145) of patients received one line and 45% (n = 120) received two or more lines. DHAP (dexamethasone, cytarabine, cisplatin) was the most commonly used salvage regimen (53%, n = 140), followed by GDP (gemcitabine, dexamethasone, cisplatin) (%, n = 60). Patients in group B were more likely to receive two or more lines of salvage therapy (54% vs. 40%; P = 0.027) and to receive GDP at relapse (48% vs. 2.2%; P < 0.001).
At the time of auto-HCT, 35.8% (n = 95) of patients were in CR and 64.2% (n = 170) in PR, with no significant differences observed between the two groups (CR: 32% in group A vs. 39% in group B; P = 0.20). The median interval from last salvage therapy to transplant for the entire cohort was 4.2 months (range, 1.5–183).
BEAM conditioning (BCNU (carmustine), Etoposide, Cytarabine, and Melphalan) was the predominant regimen overall (88%, n = 233), though its use declined in the later era (93% in group A vs. 80% in group B; P < 0.001) in parallel with a greater uptake of TEAM conditioning (Thiotepa, Etoposide, Cytarabine, and Melphalan) (7% vs. 20%, P < 0.001).
The median age at transplant was similar between groups (29.5 years in group A vs. 30.6 years in group B). Neutrophil engraftment occurred at a median of 10 days (range, 9–20), and platelet engraftment at a median of 15 days (range, 9–74), with no significant differences between the two groups.
The 3-year NRM was low across both groups but trended lower in group B (3.6% in group A vs. 1.8% in group B; P = 0.53).
Post-transplant relapse occurred less frequently in group B vs. group A (35% vs. 55%; P = 0.003), and pembrolizumab was utilized more frequently at relapse (23% vs. 4.3%; P < 0.001).
Survival and prognostic factors
At a median follow-up of 44.6 months (IQR 17.7–83.1), the median OS was 33.6 (95% CI: 26.3–53.7) months, Fig. 1. The 3-year OS for the entire cohort was 76.9% (95%CI: 71.7%−82.6%) and the 5-year OS was 67.6% (95%CI: 61.5%−74.2%). The 3-year NRM for the entire cohort was 3.4%. Survival outcomes improved significantly over time, with group B showing a significantly higher 5-year OS compared to group A (77% vs. 61.3%; P = 0.037). Group B had a higher 5-year PFS compared to group A (58% vs. 43%; P = 0.0049), Fig. 2.
Fig. 1.
Overall survival for the entire cohort. Kaplan–Meier estimate of overall survival in the entire cohort (N=265). The 5-year OS was 64.4%, and the median OS was 33.6 months (95% CI 26.3–53.7) at a median follow-up of 44.6 months (IQR 17.7–83.1). Censored patients are indicated by tick marks
Fig. 2.
Comparison of probability of overall survival between 2 eras over time. Kaplan–Meier curves comparing overall survival after autologous stem cell transplantation for relapsed/refractory Hodgkin lymphoma between Group A (2003–2015; solid blue) and Group B (2016–2020; red dashed). Survival was significantly higher in the later era (log-rank p = 0.037)
Univariable analysis identified several factors associated with improved PFS, including transplant during the 2016–2020 period (group B) (HR = 0.60; 95%CI:0.42–0.86; P = 0.005) and receipt of radiotherapy (HR = 0.69; 95%CI:0.49–0.97; P = 0.031). Conversely, inferior PFS outcomes were observed among patients who received more than one line of salvage therapy (HR = 1.49; 95%CI:1.07–2.09; P = 0.018), patients with remission duration less than 12 months after frontline therapy (HR = 1.43;95%CI:1.01–2.02, P = 0.046) and those who are in PR prior to auto-HCT (HR = 2.37;95%CI:1.59–3.54; P < 0.001). In the multivariable analysis, transplantation during the 2016–2020 period (group B) remained independently associated with improved PFS (HR = 0.56;95% CI:0.39–0.80; P = 0.002), PR at the time of auto-HCT (HR = 2.15; 95% CI:1.45–3.21; P < 0.001), and a frontline remission duration less than 12 months (HR = 1.64; 95% CI:1.15–2.35; P = 0.006), as well as receipt of ≥ 2 salvage regimens prior to auto-HCT (HR = 1.48;95% CI:1.05–2.09; P = 0.027) were independently associated with inferior PFS.
On univariable analysis, significant predictors for OS included transplant in the 2016–2020 period (group B) (HR = 0.55; 95%CI:0.34–0.90; P = 0.018) and receipt of only one line of salvage therapy (HR = 0.40; 95%CI: 0.17–0.97; P = 0.042). Factors associated with inferior OS included age ≥ 50 years (HR = 1.91; 95% CI:1.04–3.51; P = 0.037), PR prior to auto-HCT (HR = 1.99; 95% CI: 1.21–3.26; P = 0.007) (Fig. 3) and not receiving pembrolizumab posttransplant relapse (HR = 2.57, 95%CI:1.41–4.68; P = 0.002). In multivariable analysis, transplantation in the 2016–2020 period (group B) remained independently associated with superior OS (HR = 0.53; 95%CI: 0.32–0.86; P = 0.010), independent predictors of inferior OS included age ≥ 50 years (HR = 2.01; 95% CI:1.09–3.72; P = 0.026), PR prior to auto-HCT (HR = 1.98; 95% CI:1.20–3.24; P = 0.007), as summarized in [Tables 2 and 3].
Fig. 3.
Survival probability based on pre-treatment response. Kaplan–Meier estimates of overall survival according to remission status before autologous stem cell transplantation. Patients achieving complete response (CR, n = 95; 35.8%) demonstrated significantly superior survival compared with those in partial response (PR, n = 170; 64.2%) (log-rank p = 0.0057)
Table 2.
Univariate and multivariate analysis for progression free survival (PFS)
| Univariate Analysis for PFS | ||
|---|---|---|
| Variable | HR (95% CI) | P- Value |
|
Year 2003–2015 2016–2020 |
Reference 0.60 (0.42–0.86) |
0.005 |
|
Gender Female Male |
Reference 1.21 (0.87–1.69) |
0.258 |
|
Age < 50 ≥ 50 |
Reference 1.13 (0.65–1.96) |
0.666 |
|
Radiotherapy yes no |
Reference 0.69 (0.49–0.97) |
0.031 |
|
Smoking Status Ex-smoker Never Smoked Smoker |
Reference 0.94 (0.58–1.53) 1.09 (0.63–1.91) |
0.793 0.752 |
|
Comorbidities No Yes |
Reference 0.75 (0.48–1.16) |
0.191 |
|
Stage I-II III-IV |
Reference 1.23 (0.86–1.75) |
0.252 |
|
Extranodal involvement Yes No |
Reference 0.83 (0.58–1.18) |
0.292 |
|
Indication for ASCT Refractory Relapse |
Reference 0.93 (0.66–1.30) |
0.656 |
|
PFS First line ≤ 12 months > 12 months |
Reference 1.43 (1.01–2.02, p = 0.046) |
0.046 |
|
Pretransplant Response CR PR |
Reference 2.37 (1.59–3.54) |
< 0.001 |
|
Received one line of salvage regimen Yes No |
Reference 1.49 (1.07–2.09) |
0.018 |
|
Conditioning BEAM TEAM |
Reference 1.34 (0.82–2.17) |
0.241 |
| Multivariate Analysis | ||
|
Study Population 2003–2015 2016–2020 |
Reference 0.56 (0.39–0.80) |
0.002 |
|
PFS First line ≤ 12 months > 12 months |
Reference 1.64 (1.15–2.35) |
0.006 |
|
Pretransplant Response CR PR |
Reference 2.15 (1.45–3.21) |
< 0.001 |
|
Number of salvage lines 1 ≥ 1 |
Reference 1.48 (1.05–2.09) |
0.027 |
PFS progression-free survival, HR hazard ratio, CI confidence interval, ASCT autologous stem cell transplantation, CR complete response, PR partial response, BEAM carmustine (BCNU), etoposide, cytarabine (Ara-C), melphalan, TEAM thiotepa, etoposide, cytarabine, melphalan
Table 3.
Univariate and multivariate analysis for OS
| Univariate Analysis for OS | ||
|---|---|---|
| Variable | HR (95% CI) | P- Value |
|
Year 2003–2015 2016–2020 |
Reference 0.55 (0.34–0.90) |
0.018 |
|
Gender Female Male |
Reference 1.44 (0.95–2.18) |
0.088 |
|
Age < 50 > 50 |
Reference 1.91 (1.04–3.51) |
0.037 |
|
Radiotherapy No Yes |
Reference 1.47 (0.96–2.26) |
0.075 |
|
Smoking Status Ex-smoker Never Smoked Smoker |
Reference 1.04 (0.56–1.95) 1.38 (0.69–2.79) |
0.893 0.362 |
|
Comorbidities No Yes |
Reference 1.06 (0.64–1.74) |
0.820 |
|
Extranodal involvement Yes No |
Reference 0.96 (0.62–1.50) |
0.863 |
|
Indication for ASCT Refractory Relapse |
Reference 1.00 (0.66–1.52) |
0.998 |
|
PFS First line ≤ 12 months > 12 months |
Reference 1.20 (0.78–1.83) |
0.413 |
|
Pretransplant Response CR PR |
Reference 1.99 (1.21–3.26) |
0.007 |
|
Salvage treatment ≥1 1 |
Reference 0.40 (0.17–0.97) |
0.042 |
|
Conditioning BEAM TEAM |
Reference 1.46 (0.79–2.69) |
0.224 |
|
Pembrolizumab Yes no |
Reference 2.57 (1.41–4.68) |
0.002 |
| Multivariate Analysis | ||
|
Study Population 2003–2015 2016–2020 |
Reference 0.52 (0.32–0.85) |
0.009 |
|
Age < 50 > 50 |
Reference 2.00 (1.08–3.69) |
0.028 |
|
Pretransplant Response CR PR |
Reference 1.98 (1.21–3.22) |
0.006 |
PFS progression-free survival, HR hazard ratio, CI confidence interval, ASCT autologous stem cell transplantation, CR complete response, PR partial response, BEAM carmustine (BCNU), etoposide, cytarabine (Ara-C), melphalan, TEAM thiotepa, etoposide, cytarabine, melphalan
Discussion
This study spans nearly two decades and represents a comprehensive single-institution experience of auto-HCT for R/R cHL in a resource-limited setting. We observed significant improvement in survival outcomes over time, with the more recent cohort (2016–2020) demonstrating superior 5-year OS, PFS, and reduced post-transplant relapse rate compared to earlier years (2003–2015).
The improvement in 5-year OS along with a rise in 5-year PFS imparts better patient selection for transplant, better management of post-transplant relapse, and improved supportive care as reflected by lower NRM.
Pre-transplant disease status emerged as one of the most significant prognostic factors in our cohort. Patients in CR prior to auto-HCT had a markedly superior 5-year OS compared to those with PR. This observation reinforces the established role of functional imaging, particularly PET-CT, in guiding transplant decisions and underscores the clinical importance of achieving disease remission before transplant reference [20–24]. Early detection of relapse at a limited stage using routine surveillance ultrasonography combined with chest radiographs may facilitate deeper responses to salvage therapy, as recently shown in randomized and retrospective studies [25, 26]. Furthermore, contemporary salvage regimens combining BV with bendamustine have demonstrated exceptionally high CR rates (> 70%) before transplant, even in multiply relapsed patients [27, 28], offering a promising strategy for future implementation once these agents become accessible in resource-constrained settings.
During the more recent treatment era, institutional practice increasingly emphasized intensified salvage regimens to deepen responses before transplant. Patients in group B were more likely to receive two or more lines of salvage therapy, and GDP emerged as the preferred regimen due to its outpatient feasibility and favorable toxicity profile [29, 30]. Patients in group B experienced significantly lower post-transplant relapse rates and numerically higher CR rates, supporting this response-adaptive approach.
Notably, radiotherapy utilization decreased significantly in group B This reduction parallels global trends toward minimizing radiation exposure, driven by increased reliance on functional imaging and more effective systemic salvage regimens [9].
Time to relapse following first-line therapy was also a significant predictor of outcome in our analysis. Patients relapsing more than 12 months after frontline therapy had better PFS, suggesting underlying disease biology and chemosensitivity. This finding aligns with prior literature demonstrating that early relapse is associated with inferior response to salvage therapy and higher post-auto-HCT relapse rates, emphasizing the need for novel strategies in this high-risk subgroup [31, 32].
While checkpoint inhibitors were not used routinely used pre-transplant in this cohort, their post-transplant use increased significantly in patients in group B compared to group A and likely contributed to reduced mortality following relapse. Prior randomized studies have shown durable responses to checkpoint inhibitors in the post-transplant setting, particularly in patients relapsing within 1 year of auto-HCT [6, 29]. Expanding access to these agents may help mitigate the historically poor prognosis of early relapse, even where novel pre-transplant options remain limited.
Variations in conditioning regimen were observed, with an increased use of TEAM in group B, reflecting an institutional trend towards more individualized conditioning regimens, particularly for patients with borderline pulmonary function or a history of thoracic irradiation. However, due to limited sample size, no definitive conclusions can be drawn regarding the superiority of one regimen over another. Existing literature suggests BEAM and TEAM offer comparable efficacy and toxicity profiles, but larger prospective comparisons are warranted [33, 34].
in parallel with our findings, the improved survival observed in the more recent cohort (2016–2020) likely reflects broader trends in the evolving therapeutic landscape for R/R cHL. BV and ICIs, which were initially approved for post-autologous transplant relapses, demonstrated impressive response rates [35, 36] and subsequently their role expanded into earlier lines of salvage therapy, including pre-transplant settings, where PD-1 blockade has shown promise in re-sensitizing refractory disease to cytotoxic chemotherapy [37].
Although these agents were not routinely incorporated in our cohort as part of initial salvage therapy, their increased use post-transplant, particularly in the more recent cohort, may have contributed to the observed reduction in post-transplant mortality. Notably, institutional practices at KHCC during this period emphasized optimizing pre-transplant disease control, and post-transplant use of ICIs as they became more accessible. These practice shifts may have collectively contributed to the improved outcomes observed in group B, consistent with contemporary real-world reports of improved post-progression survival and long-term disease control among patients treated with novel agents and/or allogeneic transplantation [31, 38].
Despite these encouraging trends, our study has several limitations. Its retrospective nature introduces potential selection bias. Additionally, choice of salvage regimens and post-transplant therapies was not standardized and reflecting evolving institutional guidelines and physician’s preference. PET imaging, now a standard in pre-HCT assessment, was not uniformly available in the earlier period, limiting comparisons based on metabolic response. Furthermore, only patients achieving at least partial response to salvage therapy proceeded to auto-HCT; those refractory to salvage regimens were excluded, representing a selected cohort with potentially more favorable biology. This should be considered when interpreting the OS rates. Future prospective studies are needed to validate these findings, and to assess long-term outcomes of newer therapies.
Importantly, our findings reinforce the role of conventional auto-HCT even in settings with limited access to novel agents. With a 5-year OS of nearly 68% and low NRM, our experience highlights the viability of transplant as a definitive therapy in LMICs. Expansion of access to PET imaging, safer outpatient-based salvage regimens, and post-transplant ICIs could further narrow the outcome gap between LMICs and high-income countries. As such, institutions like KHCC may serve as regional models for sustainable transplant care in cHL.
Conclusion
Salvage chemotherapy and auto-HCT results in the cure of around 50% of patients with HL failing first line therapy and remains a cornerstone of treatment in regions with limited resources and novel treatment options. Our results show significant and progressive improvement in auto-HCT outcomes over the past two decades at KHCC; this is likely multifactorial and attributed to improvement in pre-transplant therapies, supportive care and lower NRM and increased utilization of post-transplant therapies namely, checkpoint inhibitors.
Author contributions
Zaid Abdel Rahman : visualization; methodology; project administration; writing – review and editing . Abeer Yaseen : Writing – original draft; data curation; visualization. Anas Zayed : data curation, Lina Alkhdour : Writing – original draft, Mona Ribie : Writing – original draft, Albatol Alamoush : Writing – original draft, Fareed Barakat: writing – review and editing . Mohammad Alrawashdeh : writing – review and editing. Alaa Abu Fara : writing – review and editing. Khalid Halahleh : writing – review and editing. Omar Shahin : writing – review and editing. Akram Al-Ibraheem : writing – review and editing, Mohammad Ma'koseh : visualization, formal analysis, methodology, writing – review and editing.
Funding
No funding was provided for this study.
Data availability
The data supporting this study’s findings are available upon reasonable request. Access to data will be granted in line with institutional policies and with approval from the King Hussein Cancer Center Institutional Review Board.
Declarations
Competing interests
The authors declare no competing interests.
Footnotes
Some of the data contained in this study were presented in an abstract format at the 2025 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, Hawai'i Convention Center, Honolulu, HI, February 12-15, 2025, Abstract # 25713.
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data supporting this study’s findings are available upon reasonable request. Access to data will be granted in line with institutional policies and with approval from the King Hussein Cancer Center Institutional Review Board.