Brazilian Experience Using High-Dose Sequential Chemotherapy Followed by Autologous Hematopoietic Stem Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma

PurposeWe evaluate the effectiveness and toxicity of high-dose sequential chemotherapy (HDS) as salvage therapy in patients with advanced-stage Hodgkin lymphoma.Patients and MethodsWe performed a retrospective analysis on 77 patients receiving HDS between 1998 and 2006. Patients enrolled were in disease progression or relapsed disease, or did not achieve a complete remission after first-line treatment. HDS consisted of the sequential administration of cyclophosphamide and granulocyte colony-stimulating factor with stem cell harvesting, followed by methotrexate plus vincristine and etoposide.ResultsThe majority of patients had stage III/IV (64%) and B symptoms (71.4%). Disease status improvement after HDS was observed in 24 of 57 patients (42%) previously in disease progression or relapse. HDS-related deaths occurred in 8 of 77 patients (10.4%). Four patients (5.2%) developed acute myeloid leukemia/myelodysplastic syndrome. Overall, disease-free and progression-free survival was 27%, 57%, and 25%, respectively.ConclusionDespite the treatment-related mortality, HDS is feasible, with satisfactory response rates, even in patients with poor prognosis.     

Effect of Routine Surveillance Imaging on the Outcomes of Patients With Classical Hodgkin Lymphoma After Autologous Hematopoietic Cell Transplantation

BackgroundPatients with relapsed and refractory classical Hodgkin lymphoma (cHL) are often treated with autologous hematopoietic cell transplantation (auto-HCT). After auto-HCT, most transplant centers implement routine surveillance imaging to monitor for disease relapse; however, there is limited evidence to support this practice.Patients and MethodsIn this multicenter, retrospective study, we identified cHL patients (n = 128) who received auto-HCT, achieved complete remission (CR) after transplantation, and then were followed with routine surveillance imaging. Of these, 29 (23%) relapsed after day 100 after auto-HCT. Relapse was detected clinically in 14 patients and with routine surveillance imaging in 15 patients.ResultsWhen clinically detected relapse was compared with to radiographically detected relapse respectively, the median overall survival (2084 days [range, 225-4161] vs. 2737 days [range, 172-2750]; P = .51), the median time to relapse (247 days [range, 141-3974] vs. 814 days [range, 96-1682]; P = .30) and the median postrelapse survival (674 days [range, 13-1883] vs. 1146 days [range, 4-2548]; P = .52) were not statistically different. In patients who never relapsed after auto-HCT, a median of 4 (range, 1-25) surveillance imaging studies were performed over a median follow-up period of 3.5 years.ConclusionA minority of patients with cHL who achieve CR after auto-HCT will ultimately relapse. Surveillance imaging detected approximately half of relapses; however, outcomes were similar for those whose relapse was detected using routine surveillance imaging versus detected clinically in between surveillance imaging studies. There appears to be limited utility for routine surveillance imaging in cHL patients who achieve CR after auto-HCT.     

自体造血干细胞移植治疗急性白血病50例临床研究

本文报告自体造血干细胞移植治疗急性白血病50例,其中,未净化自体骨髓移植(ABMT)10例,净化后自体骨髓移植(PABMT)22例,自体外周血干细胞移植(ASHSCT)18例.3年无病生存率,3组分别为75%、69.9%、72.7%.复发率分别为36.6%、27.2%、31.4%.确诊到缓解(CR)时间<2月、CR到移植时间>6月、预处理方案化疗放疗(TBI)及急性髓细胞白血病(AML)3年无病生存率较高,复发率较低.     

Favorable Outcome After Adjuvant Involved-Field Radiotherapy After Autologous Hematopoietic Stem-Cell Transplantation in Patients With High-Risk Relapsed/Refractory Lymphoma: A Single-Center Experience

BackgroundPatients with refractory or relapsed lymphoma diagnosed with bulky disease at relapse or with residual disease after salvage treatment are considered to have a dismal outcome, even after autologous hematopoietic stem-cell transplantation, as a result of disease recurrence. To minimize the risk of relapse after receipt of a transplant, involved-field radiotherapy (IFRT) to sites of either bulky or localized residual disease has been utilized; however, the ideal timing for irradiation remains controversial. The aim of this study was to assess the safety and efficacy of IFRT in the early period after transplantation.Patients and MethodsWe retrospectively evaluated the outcome of 24 autografted patients with relapsed/refractory lymphoma who presented with bulky disease at relapse or who had a persistent localized residual mass after salvage treatment and consolidated with IFRT within 4 months after autografting.ResultsNo significant toxicity was noticed during the early postradiotherapy period, while graft function was not impaired. After a median follow-up of 3 years for survivors, 21 patients were alive, 19 of whom were event free, while 2 patients died of disease recurrence and 1 died of treatment-related myelodysplastic syndrome. The 3-year overall, lymphoma relapse-free, and event-free survival rates were 86%, 86%, and 82%, respectively.ConclusionTaking into consideration the poor-risk features of the study cohort, IFRT provided early after autologous hematopoietic stem-cell transplantation showed a safe and well-tolerated toxicity profile and demonstrated long-term effective tumor control, as reflected in the promising survival rates.     

自体造血干细胞移植治疗急性白血病50例临床研究

恶性胸膜间皮瘤(MPM)的常规治疗效果不好，存在免疫抑制作用。用肿瘤浸润性淋巴细胞(TIL)抗肿瘤．是近年来过继免疫治疗的一个新途径。我们用TIL，白细胞介素2(IL-2)、干扰素(IFN)协同治疗3例MPM，初步观察效果较好。     

Are We Choosing Wisely With Autologous Hematopoietic Cell Transplantation Screening? The Utility of Pulmonary Function Testing Prior to Autologous Hematopoietic Cell Transplantation

Introduction

Despite the risk of morbidity and mortality associated with autologous hematopoietic cell transplantation (ASCT), there are no clear guidelines as to how to screen for these risks. This study sought to determine the utility of pulmonary function tests (PFTs) prior to ASCT on predicting posttransplant clinical outcomes.

Repeat Treatment of Patients With Advanced Urothelial Carcinoma With Immune Checkpoint Inhibitors Following Prior Progression on a Checkpoint Inhibitor Regimen: A Case Series

IntroductionImmune checkpoint inhibitors (ICIs) have become one of the mainstays of systemic therapy for advanced urothelial carcinoma (aUC). Increasingly ICIs are also being utilized earlier in the course of UC treatment. Limited data are available regarding ICI treatment efficacy in aUC patients who have progressed on prior ICI regimens. This case series aims to address this knowledge gap.Patients and MethodsWe identified all aUC patients treated with ICI or combination following prior progression on another ICI regimen at two academic institutions. Patient demographic, clinicopathologic and treatment data were retrospectively collected from chart review at each site. Best response to ICI treatment was defined by investigator at each site.ResultsAmong 7 patients with aUC who received ICI treatment following prior progression on a different ICI regimen, radiographic response to the second ICI regimen was observed in only 1 patient (14%) treated with combination of pembrolizumab/enfortumab vedotin.ConclusionEfficacy of ICI treatment in patients who previously progressed on another ICI regimen appears limited. These observations should be validated in larger cohorts, as it is anticipated that this clinical scenario will become more common in the future.     

Prognostic Factors for the Long-Term Survival after Hematopoietic Stem Cell Transplantation in Patients with Hodgkin Lymphoma

Objectives: This study investigated the possible prognostic factors for the long-term survival (Cure Rate) of Hodgkin Lymphoma patients who underwent HSCT. Methods: This retrospective cohort study analyzed 116 Patients diagnosed with Hodgkin Lymphoma who received autologous hematopoietic stem cell transplantation (Auto-HSCT) between the years 2007 and 2014 and followed up until 2017. The information regarding patients’ survival had been collected using phone calls, and their pre-transplant information was available in the archived documents. Prognostic effects were investigated using long-term survival models. Results: Patients with obesity had five times higher odds of long-term survival (cure) than the others (P=0.06). Also, the recurrence experience after HSCT negatively impacted the curing potential by 78% (P=0.05). Also, with 32 years as the change point, patients younger than 32 had 76% fewer odds of surviving long-term (P=0.03), and Poor transfused stem cell dose of CD34+ (<0.16 × 106 cells/ml) reduced the odds of long-term survival by 92% (P=0.01). Conclusion: According to the statistical models used in this study, obesity can increase the curing potential of Hodgkin lymphoma after transplantation. Meanwhile, aging, poor transfused CD34+ cells, and recurrence after HSCT were associated with lower survival following HSCT.     

High-dose Chemotherapy Impairs Cardiac Autonomic Control of Hospitalized Cancer Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

BackgroundAutologous hematopoietic stem cell transplantation (HSCT) patients have intermediary and late cardiac autonomic dysfunction, which is an independent mortality predictor. However, it is unknown when this HSCT-related autonomic dysfunction begins during hospitalization for HSCT and whether cardiac autonomic control (CAC) is related to cardiotoxicity in these patients.Patients and MethodsCAC was assessed in 36 autologous-HSCT inpatients (HSCT group) and 23 cancer-free outpatients (CON group) using heart rate variability analysis. The HSCT group was assessed at five time-points from admission to hospital discharge during hospitalization period. The CON group was assessed once. The severity of cardiotoxicity (CTCAE 5.0) and cardiac troponin I were recorded.ResultsThe CAC was significantly reduced after high-dose chemotherapy (HDC) (reduction of MNN, SDNN, RMSSD, LFms² and HFnu, and increase of LFnu and LF/HF; P<0.05). At the onset of neutropenia, pNN50 and HFms² were also reduced (P<0.05) compared to the admission ones. Although both groups were similar regarding CAC at hospital admission, the HSCT patients showed impaired CAC at hospital discharge (P<0.05). The LF/HF was positively associated with cardiac troponin I and RMSSD was inversely associated with the severity of cardiotoxicity (P≤0.05).ConclusionCAC worsened during hospitalization for autologous-HSCT, mainly after HDC. In addition, it seems associated to early signs of cardiotoxicity in these patients.     

Impact of Treatment Beyond Progression with Immune Checkpoint Blockade in Hodgkin Lymphoma

Atypical response patterns following immune checkpoint blockade (ICB) in Hodgkin lymphoma (HL) led to the concept of continuation of treatment beyond progression (TBP); however, the longitudinal benefit of this approach is unclear. We therefore performed a retrospective analysis of 64 patients treated with ICB; 20 who received TBP (TBP cohort) and 44 who stopped ICB at initial progression (non-TBP cohort). The TBP cohort received ICB for a median of 4.7 months after initial progression and delayed subsequent treatment by a median of 6.6 months. Despite receiving more prior lines of therapy, the TBP cohort achieved longer progression-free survival with post-ICB treatment (median, 17.5 months vs. 6.1 months, p = .035) and longer time-to-subsequent treatment failure, defined as time from initial ICB progression to failure of subsequent treatment (median, 34.6 months vs. 9.9 months, p = .003). With the limitations of a retrospective study, these results support the clinical benefit of TBP with ICB for selected patients.     

A Review of Autologous Stem Cell Transplantation in Lymphoma

Purpose of Review

Chemotherapy remains the first-line therapy for aggressive lymphomas. However, 20–30% of patients with non-Hodgkin lymphoma (NHL) and 15% with Hodgkin lymphoma (HL) recur after initial therapy. We want to explore the role of high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) for these patients.

Recent Findings

There is some utility of upfront consolidation for-high risk/high-grade B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma, but there is no role of similar intervention for HL. New conditioning regimens are being investigated which have demonstrated an improved safety profile without compromising the myeloablative efficiency for relapsed or refractory HL.

Summary

Salvage chemotherapy followed by HDT and rescue autologous stem cell transplant remains the standard of care for relapsed/refractory lymphoma. The role of novel agents to improve disease-related parameters remains to be elucidated in frontline induction, disease salvage, and high-dose consolidation or in the maintenance setting.

     

Impact of Radiation Therapy After High Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation in Patients With Relapsed/Refractory Lymphomas: A Single Center Experience

IntroductionAfter high dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT), in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), involved field radiation therapy (RT) for consolidation and residual/progressive disease (PD) eradication is a common practice.Materials and methodsRetrospective single-institution cohort analysis to evaluate the impact of early RT after HDC auto-SCT.ResultsBetween 1996 and October 2019, 153 patients (43 DLBCL, 110 HL) underwent RT after HDC auto-SCT. Males 95 (62%), females 58 (38%), median age 24 years. Indications for RT was consolidation 65%: residual disease eradication 16%: and PD eradication 19%. For DLBCL, the median overall survival (OS) for the above indications was not reached (NR):NR:2 months and the KM 5-year OS was 72.6%:64.3%:12.5% respectively (P ≤ .000). Pair-wise analysis showed that consolidation versus residual disease eradication had no difference (P = .88) but both were superior to PD disease eradication (P ≤ 000 and P = .005 respectively). For HL, indication for RT was, 54%:23%:24% respectively. The median OS was NR:NR:28.8 months and KM 5-year OS was 82.3%:78%:30% respectively (P ≤ .000). Pair-wise analysis showed that consolidation versus residual disease eradication had no difference (P = .98) but both were superior to the PD eradication group (P ≤ 000). RT was well tolerated with no significant long-term toxicity.ConclusionPost HDC auto-SCT RT was well tolerated. DLBCL and HL patients with residual disease treated with the RT had similar long-term survival as those who received RT for consolidation. RT failed to improve the poor survival in patients with post-HDC auto-SCT PD.     

Allogeneic Hematopoietic Cell Transplantation for Richter Syndrome: A Single-Center Experience

Background

Recent studies have shown dismal outcomes when chronic lymphocytic leukemia progresses to Richter syndrome after patients receive ibrutinib, with a median overall survival ranging from 2.6 to 3.5 months. Published data on efficacy of allogeneic hematopoietic cell transplantation in Richter syndrome are limited to single-center case series and registry data.

Impact of Conditioning Regimen on Outcome of 2-Year Disease-Free Survivors of Autologous Stem Cell Transplantation for Hodgkin Lymphoma

BackgroundAutologous stem cell transplantation is the standard of care for patients with relapsed HL and the long-term outcomes for survivors 2 years after ASCT have not been well described. No prospective trials have compared the effect of different conditioning regimens on outcomes.Patients and MethodsWe searched the Nebraska Lymphoma Study Group database to identify patients with HL who received ASCT from 1984 to 2007. Patients were conditioned with either CBV (cyclophosphamide, carmustine, and etoposide) or BEAM (carmustine, etoposide, cytarabine, and melphalan).ResultsAt a median follow-up of 8 (range, 2-26) years, 225 patients were alive and disease-free 2 years after ASCT. Analysis was limited to these patients. At 5 years, the progression-free survival (PFS) was 92% for BEAM and 73% for CBV (P = .002) and the overall survival (OS) was 95% for BEAM and 87% for CBV (P = .07). At 10 years, the PFS was 79% for BEAM and 59% for CBV (P = .01) and the OS was 84% for BEAM and 66% for CBV (P = .02).ConclusionPatients with HL who are disease-free and alive 2 years after ASCT have favorable outcomes. We observed lower risk of progression and longer survival associated with use of BEAM vs. CBV. Patients in the BEAM group received a transplant in more recent years so we cannot exclude the possibility that the superior outcomes seen in the BEAM group are because of better supportive care, use of peripheral blood stem cell grafts, or improvements in salvage therapies before transplantation.     

Outcomes After Salvage Autologous Hematopoietic Cell Transplant for Patients With Relapsed/Refractory Multiple Myeloma: A Single-Institution Experience

BackgroundThe role of salvage autologous hematopoietic cell transplantation (sAHCT2) for patients with relapsed/refractory multiple myeloma (RRMM) in the era of modern therapeutics is unclear. As prospective data is limited, we conducted a retrospective analysis to determine the outcomes of sAHCT2.Patients and methodsWe conducted a single-institution, retrospective analysis of patients who received sAHCT2 at The Ohio State University from 2000 to 2018. Patients who received a second transplant as part of a planned tandem or autologous-allogeneic transplant were excluded.ResultsFifty-seven patients were treated with sAHCT2. Patients had a median of 2 lines of therapy after AHCT1 prior to their sAHCT2; 70% had prior immunomodulatory imide drugs, 82% had prior proteasome inhibitor, and 20% had prior anti-CD38 monoclonal antibodies as part of re-induction therapy. Forty-two percent of patients attained ≥VGPR prior to sAHCT2. Seventy-four were treated with melphalan 200 mg/m² as conditioning regimen before infusion of a median of 3.8 × 10⁶ CD34+ cells/kg. Fifty-eight percent patients had maintenance therapy and 81% patients attained CR/VGPR as the best response after sAHCT2. The median PFS and OS after sAHCT2 were 1.6 and 3.6 years, respectively. On multivariable analysis, high-risk cytogenetics, not having attained CR/VGPR, and having more than 2 lines of therapy post-AHCT1 were associated with inferior PFS. Melphalan 140 mg/m² compared to melphalan 200 mg/m² and no maintenance therapy compared to maintenance therapy were not associated with inferior PFS. There was no transplant-related mortality in this patient cohort.ConclusionsFor MM patients deriving durable remission after their AHCT1, sAHCT2 was safe and resulted in deep and durable remissions.     

Superior Long-Term Outcome of Patients With Early Transformation of Non-Hodgkin Lymphoma Undergoing Stem Cell Transplantation

BackgroundTransformed non-Hodgkin's lymphoma arising from follicular lymphoma (TL) carries a poor prognosis with a median survival time after transformation reported to be approximately 1 year.Patients and MethodsFifty-one consecutive patients with TL received SCT between January 2000 and December 2010 (autologous SCT, n = 44, allogeneic SCT, n = 7).ResultsThirty-six (70.5%) patients had an early transformation, defined as histologic evidence of transformation at the time of initial diagnosis or transformation within 1 year of follicular lymphoma. Fifteen patients had early stage disease (29%) and 36 (71%) had advanced stage disease on presentation. At the time of analysis, 37 patients were alive with an estimated 5-year overall survival (OS) and event free survival (EFS) of 61.8% and 45%, respectively. OS and EFS were not significantly different between types of transplant procedure. The major cause of transplant failure was disease recurrence, with estimated 2-year relapse rate of 37.4%. Importantly, early transformation was independently associated with improved OS (hazard ratio [HR] 3.29; P = .028) and EFS (HR 2.49; P = .029).ConclusionOur results indicate that an aggressive transplant approach should be considered first in patients with TL and emphasize the need to incorporate novel strategies (eg, immunomodulation) early post-SCT to prevent relapses as disease recurrence remains the major cause of failure in heavily pretreated patients.     

自体干细胞移植治疗T细胞淋巴瘤31例临床分析

目的 探讨自体干细胞移植治疗T细胞淋巴瘤的疗效和其预后因素.方法 回顾性分析31例给予自体干细胞移植治疗的T细胞淋巴瘤的临床资料,观察3年总生存率和无进展生存率,分析一般状况(PS)、乳酸脱氢酶(LDH)、移植前状况、分期、外周T细胞淋巴瘤预后指数(PIT)评分对生存的影响.结果 全组中位随访时间为28(5～68)个月...     

Autologous Hematopoietic Cell Transplantation in Patients With Multiple Myeloma: Effect of Age

BackgroundIn the novel and pre–novel agent era, high-dose therapy, followed by autologous hematopoietic cell transplantation (AHCT), has been shown to prolong survival in patients with multiple myeloma (MM) in randomized trials. However, these trials only included patients aged ≤ 65 years. Given that the median age at diagnosis is 66 years, it is important to know the outcomes of AHCT in older patients. Similarly, definite outcomes of AHCT in very young patients (aged < 50 years) are also lacking because they represent a very small proportion of patients in clinical trials.Materials and MethodsWe analyzed a consecutive cohort of patients with MM receiving AHCT from 2000 to 2015 in 2 different age groups, older (> 70 years) and younger (≤ 50 years), and compared the outcomes. The primary objectives were to assess overall survival, progression-free survival (PFS), and nonrelapse mortality in these 2 groups.ResultsOf the 191 patients, 86 were young (age ≤ 50 years) and 105 were old (age > 70 years). The younger patients had better performance status and a lower comorbidity index, and most of the older patients had received a melphalan dose of 140 to 180 mg/m². The median follow-up period for the young group was 33 months (range, 2-164 months) compared with 22.5 months (range, 3-133 months) in the old group (P = .02). The PFS rate at 1 year was 60% (95% confidence interval [CI], 46%-72%) for the young group and 58% (95% CI, 45%-69%) for the old group. The overall survival rate at 1 year was 92% (95% CI, 84%-96%) for the young group and 85% (95% CI, 76%-91%) for the old group. On multivariate analysis, age did not have any effect on survival (P = .82); however, the patients with high-risk cytogenetics (hazard ratio [HR], 2.2; 95% CI, 1.06-4.6; P = .04) had worse overall mortality. High-risk cytogenetics (HR, 1.2; 95% CI, 1.1-3.5; P = .004) and no disease response or progressive disease at transplantation (HR, 5.0; 95% CI, 1.8-13.5; P = .02) were significantly associated with worse PFS.ConclusionAge should not be a limiting factor in considering the modality of AHCT. However, younger patients might also benefit from additional novel treatment approaches in the setting of clinical trials, given their similar outcomes with the older patients in our study.     

自体外周血造血干细胞移植治疗难治性恶性淋巴瘤的临床疗效

目的：探讨自体外周血造血干细胞移植（APBSCT）治疗难治性恶性淋巴瘤的临床疗效。方法：APBSCT治疗难治性恶性淋巴瘤26例,采用CHOP方案化疗加G-CSF动员外周血造血干细胞。结果：26例患者中25例获造血重建,16例获CR（61.53%）,9例PR（34.61%）,1例死于肝静脉闭塞,移植组3年无病生存率达41.70%。结论：对APBSCT治疗难治性恶性淋巴瘤具有较好疗效。明显优于常规化疗。     

造血干细胞移植治疗外周T 细胞淋巴瘤的进展

外周T 细胞淋巴瘤（PTCL）,其免疫表型提示来源于胸腺后（或成熟）T 细胞,包括大组非特异性PTCL。在全球范围内,PTCL约占非霍奇金淋巴瘤（NHL ）的10％,在我国约占20% ～30% ,明显高于西方国家。大多数PTCL侵袭性强,恶性程度高,传统的化疗方法与B 细胞NHL 相比疗效不佳、预后不良,５年生存率低。近年来研究表明造血干细胞移植（HSCT）对PTCL有较好的疗效,优于传统的化疗方法。本文主要总结自体造血干细胞移植（ASCT）、异基因造血干细胞移植（allo-SCT ）和自体外周血干细胞移植联合自体骨髓移植（APBHSCT+ABMT）三种方式及其优劣。ASCT无供受者之间的免疫排斥反应,造血重建快,但其复发率相对较高;allo-SCT 具有移植物抗淋巴瘤作用,但其有较高的治疗相关死亡率;APBHSCT+ABMT对于年龄偏大、造血功能差而难以采集足够外周血干细胞、有潜在出血和感染风险较大PTCL患者意义较大。HSCT的移植方法、移植时机、预处理方案及强度等多种因素对移植疗效均有影响,如何根据不同PTCL患者的具体情况选择不同的移植方式、选择合适的移植时机等问题还值得进一步深入的研究。