The role of routine imaging procedures in the detection of relapse of patients with Hodgkin lymphoma and aggressive non-Hodgkin lymphoma

Despite improved initial therapies, a subgroup of patients with aggressive non-Hodgkin (A-NHL) and Hodgkin lymphomas (HL) will relapse after first remission. The optimal follow-up strategy for the detection of relapse has not been clarified and periodic imaging is not recommended in most written guidelines. We identified 125 patients with HL and A-NHL diagnosed between January 1993 and September 2008 who relapsed at least 1 month after the end of initial therapy. We assessed whether relapse was detected based on clinical signs or periodic computed tomography (CT), [¹⁸F] fluorodeoxyglucose positron emission tomography (PET), or combined PET/CT and whether the mode of detection influenced the pattern and outcome of relapsed disease. Overall, most relapses (62%) were diagnosed clinically especially in A-NHL and in patients with extranodal involvement at diagnosis (p < 0.05); however, relapses of HL occurring after 2001 when PET/CT became available were more commonly detected by routine imaging (p < 0.05). Imaging-detected relapse was not associated with improved survival. While clinical exam remains the most common mode of detecting relapse, our results suggest a potential role for routine PET/CT surveillance in HL patients; however, survival does not appear to be affected by mode of detection.     

Utility of routine surveillance imaging for diffuse large B-cell lymphoma post autologous transplant: A single center experience

Surveillance scans after autologous stem cell transplant (auto-HCT) for patients with relapsed/refractory (RR) diffuse large B Cell lymphoma (DLBCL) have no proven survival benefit. We studied survival differences among patients with RR DLBCL post auto-HCT whose recurrences were detected clinically versus with routine surveillance imaging. Among the 139 patients with RR DLBCL that underwent auto-HCT from 2000 to 2014 at our institution, 37 relapsed: 21 clinical and 16 radiological. The median time to progression was 167?days for the clinical cohort and 565?days for the radiological cohort (p?=?0.03), and median overall survival (OS) was 587?days and not reached, respectively (p?=?0.006). Most patients with relapsed DLBCL after auto-HCT were diagnosed clinically and were likely to be detected earlier and have a shorter OS. Relapse in patients with aggressive disease will likely be detected when clinically apparent, and the outcome of these patients is independent of the way the relapse is diagnosed. Thus, universal scanning after auto-HCT appears to have little benefit.     

Hodgkin lymphoma patients in first remission: routine positron emission tomography/computerized tomography imaging is not superior to clinical follow‐up for patients with no residual mass

There is no consensus regarding optimal follow‐up mode for Hodgkin lymphoma (HL) patients that achieve complete remission following chemotherapy or combined chemo‐ and radiation therapy. Several studies demonstrated high sensitivity of positron emission tomography/computerized tomography (PET/CT) in detecting disease progression; however, these techniques are currently not recommended for routine follow‐up. This retrospective study conducted in two Israeli (N = 291) and one New Zealand academic centres (N = 77), compared a group of HL patients, followed‐up with routine imaging every 6 months during the first 2 years after achieving remission, once in the third year, with additional dedicated studies performed due to symptoms or physical findings (Group I) to a group of patients without residual masses who underwent clinically‐based surveillance with dedicated imaging upon relapse suspicion (Group II). Five‐year overall survival (OS) was 94% and median time to relapse was 8·6 months for both modes. Relapse rates in Groups I and II were 13% and 9%, respectively. During the first 3 years of follow‐up, 47·5 and 4·7 studies were performed per detected relapse in Groups I and II, respectively. The current study demonstrated no benefit in either progression‐free survival (PFS) or OS in HL patients followed by routine imaging versus clinical follow‐up. The cost was 10 times higher for routine imaging.     

Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma

The treatment of patients with relapsed and refractory Hodgkin lymphoma (HL), especially those who relapse after autologous stem cell transplantation, remains challenging. Patients with HL whose disease relapses after stem cell transplantation are rarely cured with current treatment modalities, and have a median survival of less than 3 years. Since no new drugs have been approved by the FDA for HL in more than three decades, there is a clear unmet medical need for drug development for this patient population. New treatment strategies that are based on targeting oncogenic signaling pathways are currently explored. This review will focus on emerging new treatment modalities that are currently under investigation for patients with relapsed classical HL.     

Hodgkin lymphoma: 2014 update on diagnosis,risk‐stratification,and management

Disease overview: Hodgkin lymphoma (HL) is an uncommon B‐cell lymphoid malignancy affecting 9,200 new patients annually and representing approximately 11.5% of all lymphomas in the United States. Diagnosis: HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte‐predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte‐rich HL are subgroups under the designation of classical HL. Risk stratification: An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy. Risk‐adapted therapy: Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved‐field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Management of relapsed/refractory disease: High‐dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, palliative chemotherapy, nonmyeloablative allogeneic transplant, or participation in a clinical trial should be considered. Am. J. Hematol. 89:772–779, 2014. © 2014 Wiley Periodicals, Inc.     

Managing relapsed and refractory Hodgkin lymphoma

Despite a high curability rate, some patients with Hodgkin lymphoma (HL) fail to respond to, or relapse after, primary conventional treatment. This review aims to identify prognostic factors at relapse and guidelines for treatment in relapsed HL. Patients with relapsed HL should be identified according to their prognostic factors at relapse (duration of remission and extranodal disease or stage). This enables relapsing patients to be separated in to three different prognostic groups; primary refractory patients should be included in the unfavourable group because of their poor prognosis. All relapsed HL should receive second-line chemotherapy and the response to this chemotherapy is crucial for the outcome. Benefit of autologous stem-cell transplantation (ASCT) has been shown in a large randomized study and, although is often proposed in relapsed HL, it may be not necessary in the rare group of patients with stage I/II and late relapse who can receive additional radiotherapy after response to chemotherapy. Patients with intermediate and unfavourable relapse should receive high-dose chemotherapy and ASCT when chemosensitive; the first goal is to achieve this chemosensitivity. For patients in the unfavourable group, including refractory patients, the role of tandem HDT or allogeneic SCT will be discussed and should be proposed for patients not in complete remission at the time of HDT.     

Modern principles in the management of nodular lymphocyte-predominant Hodgkin lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a unique rare subtype of Hodgkin lymphoma (HL) which differs clinically, pathologically and biologically from classic HL, warranting a nuanced approach to treatment. CD20 expression by malignant lymphocyte-predominant cells, a tendency for late relapses, and the risk of transformation to aggressive large B-cell lymphoma are characteristic features with important implications for treatment and follow-up. Recognition of histopathological variant patterns is also critical, with important implications for prognosis and treatment. The optimal management for NLPHL is unclear and opinions differ as to whether treatment paradigms should be similar to, or differ from, those for classic HL. Therapy differs for early versus advanced stage disease and for frontline versus relapsed or refractory disease. Potential treatment strategies include radiotherapy, combined modality therapy, chemotherapy, rituximab and watchful waiting. Given the excellent overall survival of NLPHL, treatment choices should be geared towards reducing long-term toxicity and optimizing survivorship. In this review, we provide an overview of the current literature and discuss modern principles in the management of NLPHL.     

Relapsed or poorly responsive nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents – a report from the United Kingdom's Children's Cancer and Leukaemia Study Group

There is a paucity of data on the treatment outcome in children with relapsed or poorly responsive nodular lymphocyte predominant Hodgkin lymphoma (nLPHL). This retrospective report evaluates the treatment outcome in a national cohort of children with relapsed or poorly responsive nLPHL. A total of 37 patients, 22 with relapsed and 15 with poorly responding disease, are the subjects of this report. Of the 22 patients with relapsed nLPHL, 11 had relapsed after primary excision biopsy, 10 after chemotherapy and 1 after chemotherapy and involved field radiotherapy. The majority had localized disease at relapse. The median time to relapse was 8 months after chemotherapy and 11 months after excision biopsy. Seven of the 15 patients with poorly responding nLPHL had variant histology. Three patients with initial poor response did not receive any further treatment and have had no disease progression. Transformation to diffuse large B cell lymphoma, in addition to evolution from typical to variant nLPHL occurred in one patient each. Thirty‐four patients have been successfully re‐treated with second chemotherapy or radiotherapy. Multiple relapses were uncommon but treatable. Relapse or poorly responsive nLPHL is fully salvageable with either additional chemotherapy and or radiotherapy.     

Limited clinical benefit for surveillance PET-CT scanning in patients with histologically transformed lymphoma in complete metabolic remission following primary therapy

The optimum follow-up of patients with transformed indolent lymphoma (TrIL) is not well defined. We sought to determine the utility of surveillance positron emission tomography-computed tomography (PET-CT) in patients with TrIL achieving complete metabolic remission (CMR) after primary therapy. We performed a retrospective analysis of patients with TrIL treated at Peter MacCallum Cancer Centre between 2002 and 2012 who achieved CMR after primary therapy who had ≥1 subsequent surveillance PET-CT. Of 55 patients with TrIL, 37 (67 %) received autologous stem cell transplantation as consolidation following chemoimmunotherapy. After a median follow-up of 34 (range 3–101)?months, the actuarial 3-year progression-free (PFS) and overall survival (OS) were 77 % (95 %CI 62–86 %) and 88 % (75–94 %), respectively. Of 180 surveillance PET-CT scans, there were 153 true negatives, 4 false positives, 1 false negative, 7 indeterminate and 15 true positives. Considering indeterminate scans as false positives, the specificity of PET-CT for detecting relapse was 94 %, sensitivity was 83 %, positive predictive value was 63 % and negative predictive value was 98 %. All seven subclinical (PET detected) relapses were of low-grade histology; in contrast, all nine relapses with diffuse large B cell lymphoma (DLBCL) were symptomatic. In our cohort of patients with TrIL achieving CMR, PET-CT detected subclinical low-grade relapses but all DLBCL relapses were accompanied by clinical symptoms. Thus, surveillance imaging of patients with TrIL achieving CMR is of limited clinical benefit. PET-CT should be reserved for evaluation of clinically suspected relapse.     

Clinical characteristics and outcomes of patients with Hodgkin lymphoma with central nervous system involvement: An international multicenter collaboration

Central nervous system (CNS) involvement is rare in patients with Hodgkin lymphoma (HL). Thus, the clinical features and outcomes are not well described. Cases of histologically confirmed CNS HL diagnosed between 1995 and 2015 were retrospectively identified in institutional (n = 7), national (n = 2), and cooperative group (n = 1) databases. We screened 30,781 patients with HL in our combined databases and identified 21 patients meeting eligibility criteria, an estimated frequency of 0.07%. CNS involvement was present at initial diagnosis in 10 patients (48%) and a feature of relapsed/refractory disease in 11 (52%). Among these 11 patients, the median time from initial diagnosis of HL to development of CNS involvement was 1.9 years (range 0.4–6.6) and the median number of prior lines of therapy was 2 (range 1–7). Altogether, treatments included radiation, multiagent systemic chemotherapy, combined modality therapy, and subtotal resection. The overall response rate was 65%. After a median follow‐up of 3.6 years (range 0.8–13.2) from diagnosis of CNS HL, the median PFS and OS were 7.6 and 29 months, respectively. CNS involvement as a feature of relapsed/refractory disease was adversely prognostic for both PFS and OS; however, four patients remain alive and free of relapse at 7–78 months follow‐up. CNS involvement in HL is exceedingly rare and has a distinct clinical presentation with predilection for parenchymal lesions with dural extension. Around one‐quarter of patients, mostly with CNS involvement at initial HL diagnosis, experience prolonged disease‐free survival. Am. J. Hematol. 91:894–899, 2016. © 2016 Wiley Periodicals, Inc.     

The role of hematopoietic stem cell transplantation for relapsed and refractory Hodgkin lymphoma

The optimal treatment strategy with the use of hematopoietic stem cell transplantation (HSCT) for relapsed and refractory Hodgkin lymphoma (HL) remains unclear. We performed a retrospective analysis using registry data from the Japanese Society for Hematopoietic Cell Transplantation. Adult patients with HL who underwent a first autologous or a first allogeneic HSCT between 2002 and 2009 were included. Patients who underwent HSCT in first complete remission (CR) were excluded. Autologous and allogeneic HSCT were performed in 298 and 122 patients, respectively. For autologous HSCT, overall survival at 3 years (3yOS) was 70%, and sex, age, disease status, and performance status (PS) at HSCT were prognostic factors. OS was favorable even in patients who underwent autologous HSCT in disease status other than CR. For allogeneic HSCT, 3yOS was 43%, and sex and PS at HSCT were prognostic factors. Disease status at HSCT, previous autologous HSCT, and conditioning intensity did not affect OS. Moreover, graft‐versus‐host disease did not affect progression‐free survival or relapse/progression rate. A first allogeneic HSCT without a previous autologous HSCT was performed in 40 patients. 3yOS was 45%, and was significantly inferior to that in patients who underwent their first autologous HSCT. This result was retained after the correction by the different patient characteristics according to the type of HSCT. In conclusion, autologous HSCT is effective in prolonging survival in patients with relapsed and refractory HL. Allogeneic HSCT might be beneficial even to relapsed HL after autologous HSCT, although establishing the role of allogeneic HSCT remains a challenge. Am. J. Hematol. 90:132–138, 2015. © 2014 Wiley Periodicals, Inc.     

Treatment outcome in children and adolescents with relapsed Hodgkin lymphoma – results of the UK HD3 relapse treatment strategy

The purpose of this national retrospective study was to evaluate the outcome in children with relapsed or primary refractory Hodgkin lymphoma [HL] after a primary chemotherapy alone treatment strategy. Between 2000 and 2005 , 80 children with relapsed [n = 69] or primary refractory [n = 11] HL were treated on a standardized treatment protocol of 4–6 cycles of EPIC [etoposide, prednisolone, ifosfa3mide and cisplatin] chemotherapy. Radiotherapy was recommended to all relapsed sites. High dose therapy with stem cell rescue [SCT] was recommended for patients with poor response. The 5‐year overall survival [OS] and progression‐free survival from relapse was 75·8% [64·8–83·9] and 59·9% [48·3–69·7] respectively. Duration of first remission was strongly associated with OS; risk of death was decreased by 53% [Hazard ratio (HR): 0·47, 95% confidence interval (CI): 0·19–1·18] for those with a time from end of treatment to relapse of 3–12 months (compared to <3 months) and reduced by 80% (HR 0·20, 95% CI: 0·04–0·90) for those >12 months after end of treatment. Other poor prognostic factors included advanced stage disease at relapse and B symptoms at first diagnosis. The most important factor associated with salvage failure was time to relapse . Survival outcome in children with primary refractory HL is poor.     

Novel treatment concepts in Hodgkin lymphoma

Treatment of classical Hodgkin's lymphoma (HL) has been a success story, with cure of localized disease with radiotherapy in the 1930s, cure of advanced stages with combination chemotherapy with/without radiotherapy in the mid‐1960s and continuous improvements since then. Nonetheless, at present approximately 2% of patients with classical HL are primarily refractory to conventional therapy with only 50% becoming long‐term survivors. Another 13% of patients relapse, with only 60% being alive 10 years postrecurrence (as exemplified in this review in a Swedish cohort of 18‐ to 65‐year‐old patients diagnosed during the period 1992–2009). Recently, novel targeted drugs were approved for refractory/relapsed HL and here we review results of trials that form the basis for these approvals as well as new trials. In summary, brentuximab vedotin can be used in refractory patients (i) as a complement to high‐dose chemotherapy with autologous stem cell transplantation (SCT) improving the chances of being able to proceed to an allogenic SCT and cure, (ii) as consolidation after autologous SCT and (iii) as palliative life‐prolonging treatment. However, we have yet to determine whether this drug provides the greatest benefit in first‐ or second‐line treatment, as consolidation or in refractory disease or relapse. Trials of immune checkpoint inhibitors, such as those targeting programmed death 1 (nivolumab and pembrolizumab), and thus not primarily the tumour cells, have shown overall response rates of >65%. Long‐term results and data from Phase III trials are still lacking, but nivolumab recently gained approval in refractory patients already treated with brentuximab vedotin and autologous SCT. Other novel treatments of interest include T cells with a chimeric antigen receptor and combination therapies with histone deacetylase inhibitors.     

Pretransplant FDG‐PET in aggressive non‐Hodgkin lymphoma: systematic review and meta‐analysis

This study aimed to systematically review and meta‐analyze the value of pretransplant FDG‐PET in predicting outcome after autologous stem cell transplantation in aggressive non‐Hodgkin lymphoma. MEDLINE was systematically searched; included studies were methodologically assessed and meta‐analyzed, when possible. Overall methodological quality of included studies (n = 11) was poor, with moderate risk of bias in the domains of study participation (n = 7) and prognostic factor measurement (n = 7), and high risk of bias in the domains of outcome measurement (n = 10), and study confounding (n = 11). In all aggressive non‐Hodgkin lymphomas, pooled sensitivity and specificity were 54.0% and 73.1% in predicting treatment failure, and 54.5% and 68.7% in predicting death. Because of interstudy heterogeneity, additional subgroup analyses were performed. In newly diagnosed aggressive non‐Hodgkin lymphoma, pooled sensitivity and specificity were 20.0% and 70.0% in predicting treatment failure, and 8.3% % and 30.5% in predicting death. In refractory/relapsed aggressive non‐Hodgkin lymphoma, pooled sensitivity and specificity were 68.1% and 72.1% in predicting treatment failure, and 77.3% and 69.6% in predicting death. At present, pretransplant FDG‐PET cannot be recommended in aggressive non‐Hodgkin lymphoma, because available studies suffer from major methodological flaws, and reported prognostic estimates are low (i.e., poor in newly diagnosed and moderate in refractory/relapsed aggressive non‐Hodgkin lymphoma).     

Therapy of relapsed Hodgkin lymphoma

The majority of patients who are diagnosed with Hodgkin lymphoma (HL) will be cured with primary chemotherapy. For those who relapse, autologous stem cell transplantation (ASCT) has become the standard of care. Randomized clinical trials have demonstrated that approximately 50% of patients with chemosensitive relapsed HL can achieve long term disease free survival with ASCT. However, optimal therapy of those who have chemorefractory disease or who relapse after an ASCT has not been established. Reduced intensity allogeneic stem cell transplantation may benefit these patients, although a definite graft versus HL effect has not been demonstrated and treatment-related mortality remains relatively high. New salvage regimens that incorporate gemcitabine, vinorelbine, rituximab, and/or monoclonal antibodies against CD30 are being investigated.     

Phase IA/II,multicentre, open‐label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non‐Hodgkin or Hodgkin lymphoma

Despite advancements in the treatment of non‐Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), patients continue to relapse and thus a need for new targeted therapies remains. The CD40 receptor is highly expressed on neoplastic B cells and activation leads to enhanced proliferation and survival. Lucatumumab (HCD122) is a fully human antagonistic CD40 monoclonal antibody. A phase IA/II study was designed to determine the maximum tolerated dose (MTD) and activity of lucatumumab in patients with relapsed/refractory lymphoma. Determination of the MTD was the primary objective of the phase IA dose escalation portion and clinical response was the primary objective of the phase II dose expansion portion. Patients received escalating doses of lucatumumab administered intravenously once weekly for 4 weeks of an 8‐week cycle. MTD was determined at 4 mg/kg of lucatumumab. A total of 111 patients with NHL (n = 74) and HL (n = 37) were enrolled. Responses were observed across various lymphoma subtypes. The overall response rate by computed tomography among patients with follicular lymphoma (FL) and marginal zone lymphoma of mucosa‐associated lymphatic tissue (MZL/MALT) was 33·3% and 42·9%, respectively. Lucatumumab demonstrates modest activity in relapsed/refractory patients with advanced lymphoma, suggesting that targeting of CD40 warrants further investigation.     

Hodgkin lymphoma: 2012 update on diagnosis,risk‐stratification,and management

Disease overview: Hodgkin lymphoma (HL) is an uncommon B‐cell lymphoid malignancy affecting 9,000 new patients annually and representing approximately 11% of all lymphomas in the United States. Diagnosis: HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte‐rich HL are subgroups under the designation of classical HL. Risk stratification: An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence are used to optimize therapy for patients with limited or advanced stage disease. Risk‐adapted therapy: Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved‐field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Management of refractory disease: High‐dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, palliative chemotherapy, non‐myeloablative allogeneic transplant or participation in a clinical trial should be considered. © Am. J. Hematol. 87:1096–1103, 2012. VVC 2012 Wiley Periodicals, Inc.     

Brentuximab vedotin prior to allogeneic stem cell transplantation in Hodgkin lymphoma: a report from the EBMT Lymphoma Working Party

Brentuximab vedotin (BV) is an anti‐CD30 antibody‐drug conjugate. Preliminary data suggest that BV might improve outcomes after allogeneic stem cell transplantation (SCT) for Hodgkin lymphoma (HL) when used as pre‐transplant salvage therapy. Between 2010 and 2014, 428 adult patients underwent an allogeneic SCT for classical HL at participating centres of the European Society for Blood and Marrow Transplantation. We compared the outcomes of 210 patients who received BV prior to allogeneic SCT with that of 218 patients who did not receive BV. The median follow‐up for survivors was 41 months. Patients in the BV group were more heavily pre‐treated (median pre‐allograft treatment lines: 4 vs. 3). The two groups were comparable in terms of disease status, performance status, comorbidities, prior autologous SCT, type of donor, conditioning and in vivo T cell depletion. In multivariate analysis, pre‐allograft BV had no impact on acute graft‐versus‐host disease (GVHD), non‐relapse mortality, cumulative incidence of relapse, progression‐free survival or overall survival (OS), but significantly reduced the risk of chronic GVHD (hazard ratio = 0·64; 95% confidence interval = 0·45–0·92; P < 0·02). Older age, poor performance status, use of pre‐transplant radiotherapy and active disease at SCT adversely affected OS. Patients allografted for HL after prior exposure to BV do not have a superior outcome after allogeneic SCT except for a lower risk of chronic GVHD. However, BV may improve the outlook of allogeneic SCT by helping otherwise refractory patients to achieve a more favourable disease status, facilitating allotransplant success.     

No survival benefit associated with routine surveillance imaging for Hodgkin lymphoma in first remission: a Danish‐Swedish population‐based observational study

The use of routine imaging for patients with classical Hodgkin lymphoma (HL) in complete remission (CR) is controversial. In a population‐based study, we examined the post‐remission survival of Danish and Swedish HL patients for whom follow‐up practices were different. Follow‐up in Denmark included routine imaging, usually for a minimum of 2 years, whereas clinical follow‐up without routine imaging was standard in Sweden. A total of 317 Danish and 454 Swedish comparable HL patients aged 18–65 years, diagnosed in the period 2007–2012 and having achieved CR following ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)/BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) therapy, were included in the study. The cumulative progression rates in the first 2 years were 4% (95% confidence interval [CI] 1–7) for patients with stage I–II disease vs. 12% (95% CI 6–18) for patients with stage III–IV disease. An imaging‐based follow‐up practice was not associated with a better post‐remission survival in general (P = 0·2) or in stage‐specific subgroups (P = 0·5 for I–II and P = 0·4 for III–IV). Age ≥45 years was the only independent adverse prognostic factor for survival. In conclusion, relapse of HL patients with CR is infrequent and systematic use of routine imaging in these patients does not improve post‐remission survival. The present study supports clinical follow‐up without routine imaging, as encouraged by the recent Lugano classification.     

Reduced intensity allogeneic hematopoietic cell transplantation can induce durable remission in heavily pretreated relapsed Hodgkin lymphoma

Hodgkin lymphoma (HL) can be aggressive and intractable in some cases. Patients who relapse after autologous HCT (auto-HCT) have limited treatment options. City of Hope reports our experience in the use of reduced intensity allogeneic hematopoietic cell transplantation (allo-HCT) in 24 heavily pretreated patients with relapsed HL, between January 2003 and December 2008. The median number of prior therapies was 5; 20/24 patients had prior auto-HCT. The conditioning regimen for all patients was fludarabine and melphalan. With a median follow-up for living patients of 39.0 months, at 2 years the overall survival (OS) was 60% (95% CI 42, 72) and the progression-free survival was 27% (95% CI 22, 32). Non-relapse mortality was 13.1% (95% CI 5.1, 31.4) at 2 years. The incidence of grade II–IV aGVHD was 45.8% and 8.3% for grade III–IV. Allo-HCT in heavily pretreated relapsed Hodgkin lymphoma is feasible, tolerable, and can induce durable clinical remissions.