Abstract
High-dose chemotherapy and autologous stem cell transplant (ASCT) is the standard of care treatment in relapsed/refractory Hodgkin lymphoma (rrHL). Published long-term follow-up data concerning this modality from the Indian subcontinent is lacking. In this retrospective study, the data on adults (> 16 years) with biopsy-confirmed rrHL who were autografted from 1 January 2000 to 31 December 2021 at our transplant unit were analyzed. Progression-free survival (PFS) was defined as time from transplant to disease progression or death due to any cause. Overall survival (OS) was determined from date of transplant to date of death due to any cause. Overall, 134 patients with Hodgkin lymphoma underwent ASCT. At a median follow-up of 38.2 (range, 0.1–240) months, 5 years PFS was 45.3% (95% CI 35.4–54.4). The probability of OS at 5 years was 60.5% (95% CI 49.6–69.6). Eleven (8.2%) patients suffered transplant-related mortality by 100 days. Post-transplant persistent disease, pre-transplant serum hypoalbuminemia (< 3.5 g/dl) and chemo-resistance (< PR after last salvage regimen) of tumour at transplant were independent prognostic factors associated with worse PFS in multivariable analysis. Likewise, age ≥ 30 years, ECOG performance status ≥ 1 and residual disease after transplantation correlated with inferior OS. Long-term outcomes of rrHL patients undergoing ASCT in India match those from the developed world in the era of peripheral blood stem cell transplantation. Pre-transplant performance status, chemo-sensitivity of disease, serum albumin and post-transplant remission status determined survival in our cohort.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12288-023-01690-x.
Keywords: Hodgkin lymphoma, Auto-transplantation, Relapsed, Stem cell
Introduction
Hodgkin lymphoma (HL) constitutes 10% of all lymphomas while data from our center suggests that almost one-third are HL [1]. Combination chemotherapy with or without radiation yields high cure rates in HL [2–6]. However, up to 10% of these patients do not achieve complete remission (CR) with upfront treatment (primary refractory HL) and 20–30% relapse after attaining CR (relapsed HL) [7]. High-dose chemotherapy followed by autologous stem cell transplant (ASCT) has occupied the centre stage of treatment for relapsed or refractory HL (rrHL) over the last three decades. Two prospective phase three randomized controlled trials have concluded that the addition of ASCT to conventional chemotherapy improves progression-free survival (PFS) in this population [8, 9]. A recent meta-analysis of these two seminal studies also showed that ASCT is associated with improved PFS (Hazard ratio = 0.55) but not overall survival (OS) (Hazard ratio = 0.67) [10]. Heterogeneity in the patient (e.g., age, comorbidity), disease (advanced stage at presentation, histology) and treatment-related variables (salvage therapy, conditioning regimens, methods of disease assessment, pre-transplant, or non-transplant treatment approaches) influence replication of these data in the real world, especially in low- and middle-income countries (LMICs) countries. Nevertheless, nearly half of patients undergoing ASCT eventually relapse. Knowledge of factors that help identify patients who are likely to fail ASCT helps in the stratification of therapeutic approaches in this subgroup as we witness the evolution of newer salvage regimens and the use of novel agents (e.g., Brentuximab vedotin, immune checkpoint inhibitors) that hold the promise of improving survival when used in pre- or post-transplant setting [11].
There is limited data from LMIC on ASCT in HL with small number of patients and short follow-up [12–14]; we conducted this retrospective analysis of HL patients undergoing elective single ASCT at our institute over twenty years to assess the efficacy and safety of this modality in our population. We also analyzed the factors affecting post-transplant outcomes in this real-world cohort.
Material and Methods
Patient Selection
Adult patients (> 16 years) with biopsy-proven relapsed/ refractory HL and who underwent ASCT in our transplant unit at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences (AIIMS), New Delhi from January 1st, 2000, to December 31st, 2021, were included in this study and analyzed. Prior approval by the institutional ethics committee was obtained for this research (Ref No.: IEC- 438/07.06.2019).
Transplant Protocol
All patients underwent a protocol-defined pre-transplant evaluation to determine their fitness for ASCT and disease remission status. Hematopoietic cell transplant comorbidity index (HCT-CI) if not available was calculated retrospectively using medical history from the case record files. Ann Arbor system was most used for staging the disease. The radiological staging and response assessment was done using computed tomography (CT) scans or positron emission tomography (PET-CT). Cheson’s criteria were used to define tumor response to treatment [15]. All our patients utilized peripheral blood stem cells; harvested via peripheral or central vein following mobilization with cytokine and/or chemotherapy-based regimens with the goal to achieve at least 2 million CD34 + stem cells per kilogram of body weight. Our transplant protocol for lymphoma patients has been elaborated on previously [16]. Additionally, BEAC (BCNU, etoposide, cytarabine, cyclophosphamide) protocol was also used besides CBV (cyclophosphamide, BCNU, etoposide) and BEAM (BCNU, etoposide, cytarabine, cyclophosphamide) regimens. Patients were evaluated at day + 100 for post-transplant disease response. Follow-up data were obtained via outpatient records or telephonic communication.
Study Definitions
The early-stage disease was defined as stages 1 to 2A. Patients with stage 2B to stage 4 were classified as having the advanced disease. The primary refractory disease was defined as partial response (PR) or less with first-line therapy or progression within 3 months of completion of initial treatment. Relapse was defined as the clinical or radiological emergence of disease after achieving CR and proven by biopsy, either from 3 months to 1 year of initial treatment (early relapse) or thereafter (late relapse). Patients who achieved at least PR after the last salvage chemotherapy were termed to have chemo-sensitive disease while those who achieved less than PR were categorized as having chemo-resistant disease. The bulky disease was defined as any mass ≥ 10 cm or mediastinal mass ≥ 1/3rd of maximal thoracic diameter. Serum albumin less than 3.5 g/dl was interpreted as hypoalbuminemia. Overall survival (OS) was identified as the duration from the date of transplant till death due to any cause, last follow up or date of censor, whichever is earlier. The cutoff date for survival analysis was 31st December 2021. Progression-free survival (PFS) was measured from the date of transplant to the progression/relapse of disease or death due to any cause or last follow-up. Death within 100 days after transplant due to causes other than lymphoma was termed transplant-related mortality (TRM).
Statistical Analysis
Descriptive statistics were used to show the distribution of variables among patients. Survival time analysis was performed using the Kaplan–Meier method and survival curves were compared using the log-rank test. Prognostic factors were identified by univariate and multivariate analysis using a Cox regression model. An analysis of the factors predicting TRM in this cohort using a linear regression model was also done. Variables with a p value < 0.20 in univariate analysis were included in multivariate analysis. All statistical tests were two-sided, and p < 0.05 indicated statistical significance. Analysis was carried out using STATA v16.0 software (StataCorp, College Station, TX).
Results
Patient Characteristics
A total of 134 adult patients with relapsed/refractory Hodgkin lymphoma were autografted between the years 2000 to 2021. The patient’s demographic, disease-related, and treatment characteristics are shown in Table 1. The median age at transplantation was 26 (range 16–62) years and there were 85 (63.4%) males. The median duration of remission in those who achieved CR was 7.5 months (range 0–144) with 74 (55.2%) exhibiting early relapse. The median time from diagnosis to transplant was 25.8 (range 8.8–243.5) months and the median lines of treatment received before ASCT was 2 (range 2–4). Cytokines (GCSF ± plerixafor) were used to mobilize peripheral blood stem cells in 119 (88.8%) patients while only 15 patients underwent chemo-mobilization of stem cells. BEAM conditioning was most used in 92 (68.7%) followed by BEAC in 28 (20.9%) patients.
Table 1.
Patient characteristics
| Characteristic | N (%) |
|---|---|
| n | 134 |
| Median Age, years (range) | 26 (16–62) |
| Gender | |
| Male | 85 (63.4) |
| female | 49 (36.6) |
| Histology | |
| Mixed cellularity | 55 (41.0) |
| Nodular sclerosis | 61 (45.5) |
| Lymphocyte predominant | 2 (1.5) |
| NLPHL | 2 (1.5) |
| NOS | 14 (10.5) |
| Stage | |
| Early stage | 41 (29.6) |
| Advanced stage | 93 (70.4) |
| Bulky disease | |
| Yes | 35 (26.1) |
| No | 99 (73.9) |
| Hasenclever score | |
| 0–2 | 61 (45.5) |
| > 2 | 67 (50) |
| Not available | 6 (4.5) |
| First line chemotherapy | |
| ABVD | 120 (89.5) |
| COPP | 3 (2.2) |
| EVAP | 4 (2.9) |
| Other | 7 (5.2) |
| IFRT before ASCT | |
| Yes | 38 (28.3) |
| No | 96 (71.7) |
| Response to first line | |
| CR | 77 (57.4) |
| PR | 20 (14.9) |
| PD | 37 (21.7) |
| Duration of CR1 | |
| < 12 months | 74 (55.2) |
| ≥ 12 months | 60 (44.8) |
| Number of lines of therapy | |
| 2 | 100 (74.6) |
| 3 | 29 (21.6) |
| 4 | 5 (3.8) |
| Pre-transplant disease remission status | |
| Complete remission | 75 (56.0) |
| Partial remission | 43 (32.1) |
| Relapsed refractory | 16 (11.9) |
| Pre-transplant chemo responsiveness | |
| Chemo-sensitive | 118 (88.1) |
| Chemo-resistant | 16 (11.9) |
| ECOG at ASCT | |
| 0 | 61 (45.9) |
| ≥ 1 | 73 (54.1) |
| HCT CI | |
| 0 | 98 (73.1) |
| ≥ 1 | 34 (25.4) |
| Not available | 2 (1.5) |
| Pre-transplant serum albumin | |
| < 3.5 g/dl | 17 (12.7) |
| ≥ 3.5 g/dl | 108 (80.6) |
| Not available | 9 (6.7) |
| Year of transplant | |
| 2000–2010 | 29 (21.6) |
| 2011–2021 | 105 (78.4) |
| Mobilization regimen | |
| G-CSF only | 66 (49.3) |
| Plerixafor | 53 (39.6) |
| Chemo-mobilization | 15 (11.1) |
| Conditioning regimen | |
| BEAM | 92 (68.7) |
| BEAC | 28 (20.9) |
| LEAM | 8 (5.9) |
| CBV | 6 (4.4) |
IQR interquartile range, NLPHL nodular lymphocyte predominant Hodgkin lymphoma, NOS not otherwise specified, LDH lactate dehydrogenase, ABVD adriamycin, bleomycin, vinblastine and dacarbazine, COPP cyclophosphamide, vincristine, prednisolone and procarbazine, EVAP etoposide, vinblastine, cytarabine and cisplatin, IFRT involved field radiation therapy, CR complete remission, PR partial remission, PD progressive disease, ICE ifosfamide, carboplatin and etoposide, DHAP dexamethasone, high dose cytarabine and cicplatin, BeGVP bendamustine, gemcitabine, vinorelbine and prednisolone, MINE mitoxantrone, ifosfamide, navelbine and etoposide, BEACOPP bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisolone, GDP gemcitabine, dexamethasone and cisplatin, ECOG Eastern cooperative oncology group, HCT CI hematopoietic stem cell transplant comorbidity index, GCSF granulocyte colony stimulating factor, BEAM BCNU etoposide, cytarabine and melphalan, LEAM lomustine, etoposide, cytarabine and melphalan, CBV cyclophosphamide, BCNU and etoposide, BEAC BCNU etoposide, cytarabine and melphalan
Haematological Reconstitution and Toxicity
The median CD34 + stem cell dose transfused was 2.93 million/kg (range 1.0–9.40 million/kg) with 21 (15.6%) patients receiving inadequate stem cell doses (defined as < 2 million CD34 + cells per kg). Patients engrafted neutrophils and platelet at a median of 11 (range 8–28) and 14 (range 8–50) days respectively. The duration of neutropenia experienced was nine (range 3–28) days and all patients had at least one episode of febrile neutropenia.
The clinically detected infection (CDI) was observed in 116 (86.5%) patients and microbiologically detected infection was found in 47 (35%) patients. The focus of infection could not be identified in 16 (11.9%) patients. Patients received a median of 4 (range 2–8) intravenous antibiotics for 10 (median; range 2–27) days. Therapeutic antifungal use was seen in 49 (36.6%) patients and amphotericin B was the most used therapeutic antifungal in 33 (24.7%) of these patients.
The most common grade 3 or higher regimen-related toxicities were gastrointestinal; mucositis in 53(39.8%), diarrhoea in 28 (20.9%) and vomiting in 18 (13.6%). In our cohort, 21 (15.9%) patients developed engraftment syndrome and one (0.9%) developed HLH. Overall, 11 (8.2%) patients died within 100 days post-transplant; 10 due to neutropenic sepsis and one due to liver failure. One (1.1%) patient developed a secondary malignancy (Burkitt lymphoma) after ASCT.
Response to ASCT and Survival
Patients were evaluated at day + 100 for response to ASCT using standard criteria. 104 (77.6%) were in complete remission and 19 (14.1%) had persistent disease. 31 (23.1%) patients who had pre-transplant active disease eventually attained CR after ASCT including 11 (8.2%) patients who had a pretransplant chemo-refractory disease and attained CR due to ASCT. Sixteen (11.9%) patients had chemo-refractory disease before transplant and 11 (8.2%) out of these achieved complete remission after transplant. At a median follow-up of 38.2 (range 0.1–240) months, the median PFS was 33.7 and the median OS was 94.4 months. The 3- and 5 years PFS for our cohort was 48.4% (95% CI 38.7–57.3) and 45.3% (95% CI 35.4–54.6) respectively. Probability of overall survival at 3- and 5 years was 65.7% (95% CI 55.4–74.6) and 60.5% (95% CI 49.6–69.8) in our patient population (Fig. 1a, b). At the last follow-up, 63 (47%) patients remained in CR, 21 (15.6%) were alive with disease and 31 (28.3%) died due to progressive disease after ASCT. Overall, 52 (38.8%) patients experienced a relapse of their disease. Five (3.7%) patients were lost to follow-up during the study period.
Fig. 1.
a Kaplan Meier estimates of progression-free survival. b Kaplan Meier estimates of overall survival
Prognostic Factors Affecting PFS and OS
A univariate model demonstrating the impact of various factors affecting PFS and OS in our patient group is shown in Table 2. The ECOG performance status (PS) at transplant (PS ≥ 1), pre-transplant serum albumin levels (< 3.5 g/dl) and persistent residual disease after transplant negatively influenced both PFS and OS after ASCT. Time to first relapse (< 12 months) and response to first-line treatment (incomplete remission) adversely affected PFS alone. In addition, age ≥ 30 years was associated with inferior OS in univariate analysis.
Table 2.
Prognostic factors affecting PFS/OS in univariate analysis
| Variable | n | 3 years PFS (95% CI) | P value | 3 years OS (95% CI) | P value |
|---|---|---|---|---|---|
| Age | |||||
| (≥ 30 years vs | 50 | 46.9% (31–61%) | 0.55 | 55.9% (39–69%) | 0.01 |
| < 30 years) | 84 | 49.1% (36–60%) | 73.9% (61–83%) | ||
| Gender | |||||
| Male | 85 | 55.8% (36–71%) | 0.54 | 65.0% (52–75%) | 0.74 |
| Female | 49 | 46.2% (30–60%) | 68.1% (51–80%) | ||
| Bulky disease | |||||
| Yes | 35 | 45.5% (34–60%) | 0.37 | 65.3% (53–74%) | 0.44 |
| No | 99 | 55.8% (36–71%) | 72.4% (51–85%) | ||
| Histology | |||||
| Mixed cellularity | 55 | 60.3% (46–71%) | 0.07 | 67.4% (52–78%) | 0.47 |
| Others | 79 | 39.7% (27–51%) | 66.8% (53–77%) | ||
| Stage | |||||
| Early | 41 | 61.3% (44–74%) | 0.27 | 71.3% (53–83%) | 0.59 |
| Advanced | 93 | 43.4% (32–54%) | 65.8% (55–75%) | ||
| Time to first relapse | |||||
| > 12 months | 60 | 56.7% (41–69%) | 0.04 | 70.6% (55–81%) | 0.24 |
| < 12 months | 74 | 41.5% (29–53%) | 61.7% (47–73%) | ||
| Time from diagnosis to transplant | |||||
| ≤ 24 months | 75 | 41.3% (27–54%) | 0.19 | 56.9% (40–70%) | 0.25 |
| > 24 months | 59 | 53.7% (40–65%) | 73.9% (61–82%) | ||
| Number of lines of therapy | |||||
| 2 | 100 | 52.7% (41–62%) | 0.1 | 69.7% (58–78%) | 0.09 |
| > 2 | 34 | 37.1% (20–54%) | 54.8% (35–70%) | ||
| Response to first line therapy | |||||
| CR | 77 | 54.7% (41–66%) | 0.03 | 69.9% (56–79%) | 0.26 |
| No CR | 57 | 39.7% (25–53%) | 63.1% (47–75%) | ||
| Pretransplant chemosensitivity | |||||
| Chemo-sensitive | 118 | 49.8% (39–59%) | 0.11 | 68.1% (57–76%) | 0.79 |
| Chemo-resistant | 16 | 36.4% (14–59%) | 59.6% (30–79%) | ||
| ECOG performance status | |||||
| 0 | 61 | 70.9% (56–81%) | < 0.01 | 91.3% (80–96%) | < 0.01 |
| > 1 | 72 | 32.3% (21–44%) | 50.7% (37–62%) | ||
| Pre-transplant serum albumin | |||||
| < 3.5 mg/dl | 17 | 23.5% (7–44%) | < 0.01 | 39.7% (13–65%) | 0.006 |
| > 3.5 mg/dl | 108 | 55.1% (44–64%) | 71.7% (60–80%) | ||
| Conditioning regimen | |||||
| BEAM | 92 | 42.2% (30–53%) | 0.06 | 59.1% (46–70%) | 0.1 |
| Others | 42 | 61.7% (43–75%) | 78.1% (60–88%) | ||
| Response to transplant | |||||
| CR | 104 | 61.1% (45–70%) | < 0.01 | 77.4% (66–85%) | < 0.01 |
| No CR | 30 | 3.4% (2–15%) | 26.5% (11–43%) | ||
ECOG eastern cooperative oncology group, BEAM BCNU etoposide cytarabine melphalan, CR complete remission
In multivariate analysis (Table 3), pre-transplant hypoalbuminemia (p = 0.002), pretransplant chemo-resistance of disease (p = 0.01) and persistent disease after ASCT (p = < 0.01) were associated with inferior PFS (Supplementary Figs. 1, 2 and 3). Likewise, ECOG PS > 0 (p = 0.004), persistent disease after ASCT (p = < 0.01) and age of 30 years or more were independently associated with inferior overall survival while there was a trend toward inferior OS in patients with low pretransplant serum albumin (p = 0.06) (Supplementary Figs. 4, 5 and 6).
Table 3.
Prognostic factors affecting PFS/OS in multivariate analysis
| Survival | Prognostic factor | Hazard ratio | 95% CI | P value |
|---|---|---|---|---|
| PFS |
Pre-transplant serum albumin (≤ 3.5 mg/dl vs . > 3.5 mg/dl) |
2.75 | 1.43–5.29 | 0.002 |
|
Pre-transplant chemo-sensitivity (Chemo-sensitive vs. chemo-resistant) |
2.46 | 1.15–5.24 | 0.01 | |
|
Response to transplant (CR vs. No CR) |
12.01 | 5.83–24.75 | < 0.01 | |
| OS |
Pre-transplant serum albumin (≤ 3.5 mg/dl vs. > 3.5 mg/dl) |
2.09 | 0.96–4.54 | 0.06 |
|
Age (≥ 30 years vs. < 30 years) |
2.47 | 1.19–5.12 | 0.01 | |
| ECOG performance status (0 vs. ≥ 1) | 3.77 | 1.53–9.29 | 0.004 | |
|
Response to transplant (CR vs. No CR) |
7.81 | 3.72–16.41 | < 0.01 |
PFS progression-free survival, OS overall survival, ECOG eastern oncology cooperative group, CR complete remission
Factors Predicting Transplant-Related Mortality
In univariate analysis, an ECOG performance status of ≥ 1 was correlated with a higher likelihood of TRM at day 100. In multivariate analysis, no variable was found independently associated with TRM in our patient cohort (Table 4).
Table 4.
Predictive factors of transplant-related mortality (TRM)
| Variable | Univariate analysis OR (95% CI), P value |
Multivariate analysis OR (95% CI), P value |
|---|---|---|
| Age (≥ 30 years vs. < 30 years) | 0.30 (0.08–1.10), 0.07 | 0.30 (0.05–1.61), 0.16 |
| Gender (Male vs. Female) | 0.44 (0.12–1.55), 0.20 | 1.16 (0.21–6.23), 0.86 |
| Number of lines of therapy (2 vs. ≥ 2) | 3.66 (0.45–29.76), 0.22 | |
| Conditioning regimen (BEAM vs. Others) | 2.16 (0.44–10.55), 0.33 | |
| Mobilization regimen (G-CSF alone vs. plerixafor or chemo-mobilization) | 0.33 (0.08–1.32), 0.11 | 0.37 (0.06–2.11), 0.26 |
| Duration of first remission (≥ 12 months vs. < 12 months) | 0.24 (0.05–1.20), 0.08 | 0.13 (0.01–1.28), 0.08 |
| Pretransplant disease status (CR vs. No CR) | 0.26 (0.06–1.05), 0.05 | 0.26 (0.03–1.75), 0.16 |
| Pretransplant serum Albumin (≥ 3.5 g/dl vs. < 3.5 g/dl) | 0.51 (0.09–2.74), 0.44 | |
| ECOG PS (0 vs. ≥ 1) | 0.10 (0.01–0.83), 0.03 | 0.25 (0.02–2.60), 0.24 |
| HCT CI (0 vs. ≥ 1) | 0.91 (0.22–3.68), 0.90 | |
| Use of therapeutic antifungals (No vs. Yes) | 0.49 (0.08–1.06), 0.06 | 0.14 (0.02–1.03), 0.05 |
| Microbiologically detected infection (Yes vs. No) | 3.75 (0.89–15.80), 0.07 | 1.43 (0.23–8.69), 0.69 |
ECOG Eastern cooperative oncology group, BEAM BCNU etoposide cytarabine melphalan. HCT CI hematopoietic cell transplantation comorbidity index
Discussion
This is one of the large studies reporting outcomes of ASCT in a uniformly treated real-world cohort of adult rrHL patients from India with a median follow-up duration of approximately 38 months.
In previously published large retrospective studies, 5 years PFS has ranged from 35 to 50% and OS has varied between 40 and 60% [17–20]. Being a leading referral centre for stem cell transplantation in India, the obvious referral bias translated into a cohort with more than two-thirds of patients with advanced disease, nearly 40% patients with primary refractory disease and more than half with early relapse of HL. Although nearly 90% were transplanted with the chemo-responsive disease, ASCT seems to overcome the chemo-resistance in a significant proportion of these patients with high-risk disease, thereby, yielding a 5 years progression-free and overall survival that are comparable to recent studies from the developed world [17–21].
The TRM observed in our study is higher than what is reported from resource-rich settings [12, 13, 22]. Infectious complications were the most common cause of early mortality. Even though in multivariate analysis, we could not identify any factors that significantly affected TRM, probably due to the small sample size, a significant proportion of patients transplanted in active disease may have been a contributory factor. Improvement in supportive care, as well as more careful selection of patients, may help reduce early mortality in our setting. Notably, the microbial culture positivity of hematopoietic stem cells was not found to affect post-transplant mortality at our centre [23]. Hematopoietic reconstitution and non-haematological regimen-related toxicities (mainly gastrointestinal) were found comparable to previous studies using BEAM conditioning in lymphoma patients [24, 25]. The incidence of second malignancies reported in our series (1.1%) compares favourably to what is reported (4–9%) in larger studies [26, 27]. Overall, however, the most common cause of transplant failure in our series was disease progression (38.8%) which is comparable to published data [18, 27].
Inability to achieve remission after ASCT was an independent risk factor associated with inferior PFS and OS in our study. Patients who did not attain disease remission after ASCT had dismal outcomes with a 5 years OS of only 26.5% versus 77.4% for those who attained CR and are, therefore, candidates for clinical trials investigating novel therapeutic approaches. These results are consistent with previously reported studies [28]. The use of newer agents (BV, ICI) in the post-transplant setting has been extremely limited in our population due to poor availability and affordability. ECOG performance status of one or more at transplant was also associated with inferior OS in this series. The assessment of overall physical function as a predictor of survival is quite understandable from a pathophysiological standpoint because poorer prognoses are generally associated with significant symptoms and a greater burden of disease. Limited previous data have shown that poorer PS have a higher risk of treatment failure and worse survival after auto-transplant in HL [28–30]. Serum albumin has been correlated with survival after primary treatment of HL as a part of the international prognostic score but its association with post-transplant survival outcomes is rarely studied and mechanisms are poorly understood. Pretransplant hypoalbuminemia was associated with worse PFS in our patients. Pathobiological correlation of low serum albumin with worse survival after stem cell transplant is often believed due to the persistence of an inflammatory state secondary to active malignancy or infection. It also indicates poor nutritional status and hepatic dysfunction in heavily pre-treated patients [16, 31].
Our study sustains the existing evidence that chemo-sensitivity of disease at transplantation is an important prognostic factor. Like other published series, we show that chemo-sensitivity is an independent prognostic factor affecting survival in multivariate analysis [18, 32]. Alternative salvage approaches like allogenic stem cell transplantation or novel therapies should be preferred over ASCT in such patients. Published data are conflicting regarding the impact of the number of lines of therapy on post-transplant outcomes; we did not find any correlation among them in our cohort, probably due to the smaller sample size. Unlike previous reports, we could not correlate lymphoma stage, time to relapse and bulky disease with survival outcomes in our patient population.
This study had a few limitations. Apart from being a single centre, retrospective series, data concerning parameters like B-symptoms and extra-nodal involvement was not collected consistently and therefore could not be analyzed. This study excluded patients who were candidates for ASCT but either did not receive salvage regimens or did not complete salvage therapy due to various reasons. Therefore, our cohort represents only selected individuals who ultimately underwent ASCT. Moreover, the burden of late adverse effects of ASCT on major organ functions was not addressed in this series and warrants further studies.
In conclusion, long-term outcomes in Indian patients with relapsed refractory HL improve with auto-transplant and are comparable to international standards. Response to transplant, pretransplant hypoalbuminemia and performance status determined long-term outcomes in our patients of HL undergoing ASCT.
Supplementary Information
Below is the link to the electronic supplementary material.
Funding
None.
Declarations
Conflict of interest
No potential conflict of interest.
Ethical approval
The study is following ethical standards.
Footnotes
Sudhir Kumar is co-first author.
Publisher's Note
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Sudhir Kumar and Atul Sharma have been contributed equally to this work.
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