Management and Outcomes of Patients with Refractory Solitary Plasmacytoma after Treatment with Definitive Radiation Therapy.

PURPOSE: Radiation therapy (RT) is the standard treatment for solitary plasmacytoma (SP); however, the optimal management of RT-refractory SPs is unknown. We examined outcomes after early systemic therapy, surgical resection, or observation for patients with RT-refractory disease and assessed the potential impact of treatment selection on disease outcomes. METHODS AND MATERIALS: We retrospectively reviewed patients with SP treated with definitive radiation and evaluated at a single institution with persistent disease on imaging or biopsy. Descriptive statistics were used to characterize patient and disease characteristics and treatment outcomes. RESULTS: Of 102 total SP patients, 17 (17%) were RT-refractory. The median RT dose was 45 Gy, and median follow-up was 71 months from end of RT. Fifteen patients had additional treatment for refractory disease at a median time of 9.5 months after RT, with the following subsequent interventions: surgical resection (n = 4), additional RT (n = 2), systemic therapy without evidence of multiple myeloma (MM; n = 4), systemic therapy for progression to MM (n = 5), and observation (n = 2). Of 4 patients treated with surgical resection, 3 progressed to MM 22 to 43 months after diagnosis. Of 2 patients treated with additional RT, neither responded, and both had pathologic confirmation of residual disease after the second course. Four patients treated with systemic therapy without MM all had complete responses on positron emission tomography and no subsequent MM progression. Eight patients were initially observed after RT for ≥12 months (n = 8) or ≥24 months (n = 6). Of the 2 patients in continued observation, both had stable/unchanged avidity after radiation treatment for 12 and 22 months and ultimately had a slow decrease of disease avidity over multiple years. CONCLUSIONS: Patients with RT-refractory SPs can achieve good local control with alternative therapies, such as surgery or systemic therapy, if needed. Additional RT does not seem to be effective. Given the known high rates of progression from SP to MM, close observation of asymptomatic persistent disease until disease progression is likely sufficient in most cases.

Classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (HL) is rare disease, with an incidence of approximately 85,000 patients globally per year and a predilection for adolescents and young adults (ages 15-39). Since the introduction of combination chemotherapy in the 1960's and radiation dating back to the early 1900's, therapeutic options and by extension, clinical outcomes have improved dramatically with 5-year overall survival (OS) approaching 90% today. [1](#ref-0001) Advances in understanding HL biology have additionally facilitated development of targeted agents and immunotherapy which have further improved short and long-term outcomes. Despite continued improvements in up-front and salvage therapy, long-term survivors of HL experience several treatment-associated late toxicities, thus, along with efforts to improve therapeutic efficacy, efforts to reduce late effects remain a high-priority in the field.

Radiation Therapy Can Be Safely Incorporated into Pretransplantation Treatment Regimens for Patients with Multiple Myeloma.

Primary treatment of multiple myeloma (MM) often involves systemic induction therapy (SIT) followed by autologous stem cell transplantation (ASCT). Radiation therapy (RT) is sometimes used for palliation; however, many practitioners avoid RT out of concern that future peripheral blood progenitor cell (PBPC) collection required for ASCT may be compromised. In this study, we retrospectively examined the possible effect of RT on PBPC collection. We reviewed the charts of 732 patients with MM treated with RT at our institution from 1999 to 2017, including patients who received RT prior to PBPC collection for planned ASCT. RT plans (both MM and non-MM RT) were reviewed to estimate the percentage of bone marrow (BM) treated using published estimates of skeletal BM distribution. Statistics were performed using Pearson correlation and the t-test. The 732 MM patients included 485 planned for ASCT; of these, 223 received RT prior to PBPC collection and were included in the final cohort. The median age at PBPC collection was 59 years (range, 33 to 80 years). For SIT, patients received combination regimens including the following agents: bortezomib (142 patients; 64%), lenalidomide (111 patients; 50%), and alkylators (46 patients; 21%). Nine patients (4%) received dexamethasone alone. The median cumulative %BM treated per patient was 6.7 (range .0 to 47.4). The median RT dose was 24 Gy (range, 10.0 to 75.6 Gy). Mobilization was performed using granulocyte-colony stimulating factor (G-CSF) alone (189 patients; 85%), G-CSF with plerixafor (15 patients; 7%), or chemotherapy (19 patients; 9%). A median of 7.8 × 106 CD34+/kg PBPCs (range, .5 to 54.8× 106 CD34+/kg) were collected in a median of 3 (range, 1 to 9) apheresis procedures. One hundred ninety-six patients (99%) collected ≥2.0 × 106 CD34+/kg PBPCs, and 166 (83%) collected >5.0 × 106 CD34+/kg PBPCs. The number of PBPCs collected was not associated with %BM treated (P = .15) or RT dose (P = .56). The number of apheresis procedures performed was not associated with %BM treated (P = .54) or RT dose (P = .85). The amount of PBPCs collected did not differ significantly between patients receiving RT to the pelvis/sacrum (P = .20) and those receiving RT to the spine (P = .13). The time to platelet engraftment was longer for patients with higher %BM treated (P = .02). Eleven patients did not undergo a confirmed ASCT, owing to patient preference (3 patients), trial therapy (1 patient), comorbidities (1 patient), election for hospice (1 patient), inadequate collection (4 patients), or inadequate follow-up (1 patient). In our study cohort, RT prior to ASCT did not impair successful ASCT. RT must be carefully planned and delivered to ensure safe incorporation into pre-ASCT treatment regimens.

Impact of cumulative dose of brentuximab vedotin on outcomes of frontline therapy for advanced-stage Hodgkin lymphoma.

In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and standard dose AVD IV on days 1 and 15 of each 28-day cycle for up to 6 cycles. At the time of treatment, the median patient age was 37 years, and a high-risk International Prognostic Score was observed in 46% of patients. Overall, 91% of patients received 6 cycles of AVD; 55% of patients did not receive the intended cumulative dose of BV (CDB); 28% of patients received two-thirds or less than the planned CDB. At a median follow-up time of 27.4 months (95% confidence interval [CI], 24.8-29), the median progression-free survival (PFS) was not reached, and the 12-month PFS was 90.3% (95% CI, 85.9-95.0). The impact of CDB on PFS was not significant (P = .15), nor was high CDB significantly associated with increased adverse events. In real-world experience, A + AVD is a highly effective treatment for patients with advanced-stage cHL, including for patients with prominent dose reductions of BV.

High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma.

Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon, aggressive type of non-Hodgkin lymphoma. Rituximab-containing chemoimmunotherapy with or without radiation therapy (RT) is standard first-line treatment. Relapsed or refractory (R/R) disease has long been treated with salvage chemotherapy followed by high-dose chemotherapy (HDC), with autologous stem cell transplantation (ASCT) in appropriate patients. We retrospectively analyzed all patients with R/R PMBCL treated with HDC/ASCT at our center between January 2000 and August 2022. The 60 study patients received either rituximab-BEAM (n = 37) or rituximab-gemcitabine/busulfan/melphalan (R-GemBuMel) with or without vorinostat (n = 23), followed by ASCT. Forty-six patients received mediastinal RT, either as prior consolidation of frontline therapy or following ASCT. At median follow-up of 6 years (range, .3 to 21 years), the 5-year progression-free survival (PFS) and overall survival (OS) rates of the whole group were 58% and 77%, respectively, for the entire cohort, 51% and 65% for the R-BEAM recipients, and 69% and 82% for R-vorinostat/GemBuMel recipients. Multivariable analyses showed that a negative positron emission tomography scan at ASCT (hazard ratio [HR], .28) and involvement of only 1 organ (HR, .33) were independently associated with improved PFS. In addition, receipt of R-vorinostat/GemBuMel (HR, .23) was an independent favorable predictor of OS. Our data indicate that HDC/ASCT is effective in R/R PMBCL, with improved outcomes in patients receiving R-vorinostat/GemBuMel.

Safety of Concurrent Radiation Therapy With Brentuximab Vedotin in the Treatment of Lymphoma.

Purpose: Purpose: Radiation therapy (RT) and the antibody-drug conjugate brentuximab vedotin (BV) are standard-of-care treatment options for patients with certain B and T-cell lymphomas; however, there are limited data exploring the safety of concurrent BV and RT (BVRT). Methods and Materials: We performed a single institutional retrospective review of 44 patients who received BVRT. Results: Twenty percent of patients (9/44) developed new grade 2 or higher (G2+) hematologic toxicity (HT) after BVRT, which was associated with radiation dose (median dose of 35 Gy in those with new G2+ HT compared with 15 Gy in those without; P < .001). Acute G2+ elevation in aspartate transaminase or alanine transaminase level was associated with administration of concurrent chemotherapy with BVRT (57% vs 21%; P = .047) but was not associated with any RT factors. Local control (LC) was achieved in 24 of 42 patients (57%) with available follow-up. Ten patients (23%) proceeded to stem cell transplant or cellular therapy after BVRT at a median of 48 days (interquartile range, 27-188 days). At last follow-up, 10 patients (23%) remained without evidence of disease. Conclusions: Our analysis demonstrates that the combination of BV and RT is well tolerated, though care should be taken during RT planning to reduce the risk of HT. This combination can be considered for patients in need of both local and systemic disease control.

Radiation for hematologic malignancies: from cell killing to immune cell priming.

Over the past half-century, the role of radiotherapy has been revolutionized, in part, by a shift from intent to directly kill cancer cells to the goal of priming anti-tumor immune responses that attack both irradiated and non-irradiated tumors. Stimulation of anti-tumor immunity depends on the interplay between radiation, the tumor microenvironment, and the host immune system, which is a burgeoning concept in cancer immunology. While the interplay of radiotherapy and the immune system has been primarily studied in solid tumors, we are beginning to understand this interplay in hematological malignancies. The intent of this review is to lead readers through some of the important recent advances in immunotherapy and adoptive cell therapy, highlighting the best available evidence in support of incorporating radiation therapy and immunotherapy into the treatment of hematological malignancies. Evidence is presented regarding how radiation therapy 'converses' with the immune system to stimulate and enhance anti-tumor immune responses. This pro-immunogenic role of radiotherapy can be combined with monoclonal antibodies, cytokines and/or other immunostimulatory agents to enhance the regression of hematological malignancies. Furthermore, we will discuss how radiotherapy facilitates the effectiveness of cellular immunotherapies by acting as a "bridge" that facilitated CAR T cell engraftment and activity. These initial studies suggest radiotherapy may help catalyze a shift from using chemotherapy-intensive treatment to treatment that is "chemo-free" by combining with immunotherapy to target both the radiated and non-irradiated disease sites. This "journey" has opened the door for novel uses of radiotherapy in hematological malignancies due to its ability to prime anti-tumor immune responses which can augment immunotherapy and adoptive cell-based therapy.

Results of salvage therapy with mini-hyper-CVD and inotuzumab ozogamicin with or without blinatumomab in pre-B acute lymphoblastic leukemia.

BACKGROUND: Historically, adults with relapsed-refractory acute lymphoblastic leukemia (ALL) experienced poor outcomes with intensive chemotherapy. This mature analysis explores the benefit of the addition of sequential blinatumomab to low-intensity mini-Hyper-CVD chemotherapy with inotuzumab ozogamicin in this setting. METHODS: Mini-Hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 83% dose reduction) was combined with inotuzumab during the first 4 courses. From Patient #68 and onwards, inotuzumab was given in reduced and fractionated doses, and blinatumomab was added sequentially for 4 courses. Maintenance therapy with prednisone, vincristine, 6-mercaptopurine and methotrexate was given for 12 courses, and blinatumomab for 4 additional courses. RESULTS: Among 110 patients (median age, 37 years) treated, 91 (83%) responded (complete response, 69 patients, 63%). Measurable residual disease negativity was documented in 75 patients (82% of responders). Fifty-three patients (48%) received allogeneic stem cell transplantation (SCT). Hepatic sinusoidal obstruction syndrome occurred in 9/67 patients (13%) on the original inotuzumab schedule and in 1/43 (2%) on the modified schedule. With a median follow-up of 48 months, the median overall survival (OS) was 17 months, and the 3 year OS was 40%. The 3 year OS was 34% with mini-Hyper-CVD plus inotuzumab and 52% with additional blinatumomab (P = 0.16). By landmark analysis at 4 months, the 3 year OS was 54%, similar between patients who did or did not receive allogeneic SCT. CONCLUSION: Low-intensity mini-Hyper-CVD plus inotuzumab with or without blinatumomab showed efficacy in patients with relapsed-refractory ALL, with better survival after the addition of blinatumomab. Trial registration The trial was registered on clinicaltrials.gov with the identifier NCT01371630.

Immunophenotypic and genomic landscape of Richter transformation diffuse large B-cell lymphoma.

Integrated clinicopathological and molecular analyses of Richter transformation of diffuse large B-cell lymphoma subtype (RT-DLBCL) cases remain limited. This study group included 142 patients with RT-DLBCL. Morphological evaluation and immunophenotyping, using immunohistochemistry and/or multicolour flow cytometry, were performed. The results of conventional karyotyping, fluorescence in situ hybridisation analysis and mutation profiling performed using next generation sequencing were reviewed. Patients included 91 (64.1%) men and 51 (35.9%) women with a median age of 65.4 years (range 25.4-84.9 years) at the time of RT-DLBCL diagnosis. Patients had CLL for a median of 49.5 months (range 0-330 months) before onset of RT-DLBCL. Most cases (97.2%) of RT-DLBCL had immunoblastic (IB) morphology, the remainder had a high grade morphology. The most commonly expressed markers included: CD19 (100%), PAX5 (100%), BCL2 (97.5%), LEF1 (94.7%), CD22 (90.2%), CD5 (88.6%), CD20 (85.7%), CD38 (83.5%), MUM1 (83.3%), CD23 (77%) and MYC (46.3%). Most (51/65, 78.4%) cases had a non-germinal centre B-cell immunophenotype. MYC rearrangement was detected in 9/47 (19.1%) cases, BCL2 rearrangement was detected in 5/22 (22.7%) cases, and BCL6 rearrangement was detected in 2/15 (13.3%) cases. In comparison to CLL, RT-DLBCL had higher numbers of alterations involving chromosomes 6, 17, 21, and 22. The most common mutations detected in RT-DLBCL involved TP53 (9/14, 64.3%), NOTCH1 (4/14, 28.6%) and ATM (3/14, 21.4%). Among RT-DLBCL cases with mutant TP53, 5/8 (62.5%) had TP53 copy number loss, and among those, such loss was detected in the CLL phase of the disease in 4/8 (50%) cases. There was no significant difference in overall survival (OS) between patients with germinal centre B-cell (GCB) and non-GCB RT-DLBCL. Only CD5 expression correlated significantly with OS (HR=2.732; 95% CI 1.397-5.345; p=0.0374). RT-DLBCL has distinctive morphological and immunophenotypic features, characterised by IB morphology and common expression of CD5, MUM1 and LEF1. Cell-of-origin does not seem to have prognostic implications in RT-DLBCL.

Assessment of Lymphoma and Other Hematologic Malignancies Training Needs Among Radiation Oncology Residents: a Brief Report.

The role of radiation therapy (RT) varies across hematologic malignancies (HM). Radiation oncology (RO) resident comfort with specific aspects of HM patient management is unknown. The International Lymphoma RO Group (ILROG) assessed resident HM training opportunities and interest in an HM away elective. RO residents (PGY2-5) in the Association of Residents in RO (ARRO) database (n = 572) were emailed an anonymous, web-based survey in January 2019 including binary, Likert-type scale (1 = not at all, 5 = extremely, reported as median [interquartile range]), and multiple-choice questions. Of 134 resident respondents (23%), 86 (64%) were PGY4/5 residents and 36 (27%) were in larger programs (≥ 13 residents). Residents reported having specialized HM faculty (112, 84%) and a dedicated HM rotation (95, 71%). Residents reported "moderate" preparedness to advocate for RT in multidisciplinary conferences (3 [2-3]); make HM-related clinical decisions (3 [2-4]); and critique treatment planning (3 [2-4]). They reported feeling "moderately" to "quite" prepared to contour HM cases (3.5 [3-4]) and "quite" prepared to utilize the PET-CT five-point scale (4 [3-5]). Overall, residents reported feeling "moderately" prepared to treat HM patients (3 [2-3]); 24 residents (23%) felt "quite" or "extremely" prepared. Sixty-six residents (49%) were potentially interested in an HM away elective, commonly to increase comfort with treating HM patients (65%). Therefore, HM training is an important component of RO residency, yet a minority of surveyed trainees felt quite or extremely well prepared to treat HM patients. Programs should explore alternative and additional educational opportunities to increase resident comfort with treating HM patients.

Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma.

Despite remarkable progress in survival with the availability of novel agents, an overwhelming majority of patients with multiple myeloma (MM) have disease that relapses. Allogeneic (allo-) hematopoietic cell transplantation (HCT) is a potentially curative option for a subgroup of patients with high-risk MM. This study assessed the long-term outcome of MM patients who underwent allo-HCT while in first remission as consolidation treatment. Thirty-three patients with newly diagnosed MM who underwent allo-HCT as part of consolidation therapy between 1994 and 2016 were reviewed retrospectively. Of these patients, 70% underwent autologous HCT before allo-HCT. All patients were chemosensitive and achieved at least partial response before proceeding to allo-HCT. Most received nonmyeloablative/reduced-intensity conditioning (88%) and a matched sibling donor graft (85%). Acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 30% and 61% of patients, respectively. The median duration of follow-up was 64.1 months (range, 1.4 to 199.2 months) for all patients and 164.4 months (range, 56.0 to 199.2 months) for survivors. The median progression-free survival (PFS) was 36 months (95% confidence interval (CI), 8.6 to 73.0 months). The median time from treatment to progression was 73.0 months (95% CI, 30.6 months to not reached). The median overall survival (OS) was 131.9 months (95% CI, 38.4 months to not reached). Of all patients, 39% were alive for more than 10 years, with 46% (n = 6) without progression or relapse. The cumulative incidence of relapse was 18% at 1 year, 39% at 5 years, and 46% at 10 years post-allo-HCT. The cumulative incidence of nonrelapse mortality was 3% at 100 days, 18% at 1 year, 21% at 3 years, and 24% at 5 year post-allo-HCT. On multivariable analysis, high-risk cytogenetics were associated with a shorter PFS (hazard ratio [HR], 2.7; 95% CI, 1.01 to 7.21; P = .047) and OS (HR, 4.91; 95% CI, 1.48 to 16.27; P = .009). Achieving complete remission after allo-HCT also was associated with longer PFS (HR, 0.24; 95% CI, 0.09 to 0.64; P = .004) and OS (HR, .23; 95% CI, .07 to .72; P = .012). Allo-HCT may confer a survival advantage in a selected population of MM patients when performed early in the disease course; additional data on identifying the patients who will benefit the most are needed.

Survival Outcomes of Patients with Mycosis Fungoides Involving the External Ear and Ear Canal.

OBJECTIVES/HYPOTHESIS: Mycosis Fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. Disease involvement of specific locations may be more significant than simply the symptoms associated with that site; it is possible that involvement of certain sites could be associated with poor prognosis. We aimed to evaluate the outcomes of patients with MF with documented involvement of the EAC and external ear. STUDY DESIGN: Retrospective analysis. METHODS: We retrospectively reviewed 40 patients with MF that were treated by otologists between 2012 and 2021. RESULTS: We report the largest series of patients with MF involving the external ear and EAC. Of the 40 patients included in this study, 17 presented with Mycosis Fungoides in the otologic region (MFO). Of these 17 MFO patients, 2/17 had involvement of the external ear only, 3/17 of the EAC only, 11/17 of both the external ear and EAC, and 1/17 of the periauricular skin. Of note, 11/14 (79%) patients presenting with EAC disease died compared to11/26 (42%) of patients without involvement. In addition, eight of the 13 (62%) patients with external ear involvement died compared to 14/27 (52%) of patients without involvement. Ear canal involvement was associated with a statistically significant shorter overall survival duration in patients with MF (p = 0.03). Furthermore, disease in the EAC was found to have a hazard ratio value of 2.565 (CI 1.102-5.970). CONCLUSIONS: Involvement of the EAC by MF portends a poor prognosis. This finding highlights the need for a more in-depth otologic evaluation of patients with MF. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1486-1491, 2023.

Central Nervous System Prophylaxis and Treatment in Acute Leukemias.

OPINION STATEMENT: Improvements in systemic therapy in the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) have improved patient outcomes and reduced the incidence of CNS relapse. However, management of patients with CNS disease remains challenging, and relapses in the CNS can be difficult to salvage. In addition to treatment with CNS-penetrant systemic therapy (high-dose methotrexate and cytarabine), intrathecal prophylaxis is indicated in all patients with ALL, however is not uniformly administered in patients with AML without high-risk features. There is a limited role for radiation treatment in CNS prophylaxis; however, radiation should be considered for consolidative treatment in patients with CNS disease, or as an option for palliation of symptoms. Re-examining the role of established treatment paradigms and investigating the role of radiation as bridging therapy in the era of cellular therapy, particularly in chemotherapy refractory patients, is warranted.

Second malignancies in patients with Hodgkin's Lymphoma: Half a century of experience.

Purpose: Therapeutic improvements for Hodgkin's Lymphoma (HL) has resulted in excellent survival outcomes. Thus, patients are increasing susceptible to developing secondary malignancy (SM) a feared iatrogenic complication. Materials & Methods: We evaluated the SM risk in a cohort of patients with HL treated over a 50-year period. In total, 1653 patients were treated for HL from 1956 to 2009 at a tertiary-cancer-center. A cumulative incidence function was used to quantify SM risk and the Fine and Gray competing risk model was used to identify disease and treatment related correlates. Results: Two-hundred-ninety patients (19%) developed SMs. Paradoxically, SM risk was higher in the modern era with 20-year cumulative incidence rates of 11.1%, 11.9%, 17% and 21.8%, for patients treated <1970, 1971-1986, 1986-1995 and 1996-2009, respectively. We hypothesized that the disproportionately high rate of early deaths in the early era may skew the assessment of SM risks, a much-delayed event. When the analysis was restricted to patients with early-stage favorable HL treated >1980, we found a reversal of the trend, especially on the risk of solid tumor, with a hazard ratio of 0.57 (p = 0.0651) in patients treated after 1996. Conclusion: Our findings highlight the limitations of comparing the risk of a late event between groups with disparate rates of early deaths, despite the use of a competing risk model. When partially corrected for, patients treated in the more recent time period experienced a lower solid tumor risk.

NCCN Guidelines® Insights: Hodgkin Lymphoma, Version 2.2022.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte-predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

Autologous stem cell transplantation for large B-cell lymphoma with secondary central nervous system involvement.

Secondary central nervous system large B-cell lymphoma (SCNSL) is rare, with a generally poor prognosis. There is limited data about the role of autologous stem cell transplantation (ASCT) in these high-risk patients. We explored in this study treatment outcomes and prognostic factors for patients with SCNSL who underwent ASCT. We included all consecutive patients who underwent ASCT at our institution. Primary endpoints were progression-free survival (PFS) and overall survival (OS). One-hundred two patients were identified. Median age at transplant was 56 (range, 21-71) years. With a median follow-up of 56 (range, 1-256) months, the median PFS and OS were 40 and 88 months, respectively. The 4-year PFS and OS were 48% and 57%, respectively. In univariate analysis, complete remission (CR) at transplant, prior lines of therapy (≤2), normal lactate dehydrogenase, and parenchymal involvement were significantly associated with improved PFS. For OS, only CR at transplant and ≤2 prior lines of therapy were associated with improved survival. On multivariable analysis for PFS, CR at transplant (hazard ratio [HR], 0.278; 95% CI, 0.153-0.506; P ≤ .0001) and ≤2 prior lines of therapy (HR, 0.485; 95% CI, 0.274-0.859; P = .0131) were significantly associated with superior PFS. Similarly, CR at transplant (HR, 0.352; 95% CI, 0.186-0.663; P = .0013) and ≤2 prior lines of therapy (HR, 0.476; 95% CI, 0.257-0.882; P = .0183) were associated with improved survival. In the largest single-center study, our findings indicate that ASCT is associated with durable responses and prolonged survival in patients with SCNSL. Patients in CR at transplant and those who received ≤2 lines of therapy have particularly excellent outcomes.

MALT lymphoma of the tongue: An unusual site that may present a diagnostic challenge.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a low-grade B cell lymphoma that can affect any organ, usually preceded by acquisition of MALT in response to antigenic stimulus provided by infections or autoimmune diseases. Most often, MALT lymphoma involves the stomach (about 35% of cases), followed by the ocular adnexal region, skin, lungs, and salivary glands, but virtually any extranodal site can be involved. MALT lymphomas are less common at sites of normal MALT tissue, such as Waldeyer ring and the ileocecal region of the gastrointestinal tract. Lymphomas involving the tongue are extremely rare and represent approximately 3% of all lymphomas involving the head and neck region. In this study, we discuss potentially challenging diagnostic aspects of MALT lymphoma involving the tongue and review and summarize the available literature about this topic.

Improved outcomes of high-risk relapsed Hodgkin lymphoma patients after high-dose chemotherapy: a 15-year analysis.

High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment for chemosensitive relapsed classical Hodgkin lymphoma, although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR classical Hodgkin lymphoma patients treated with HDC/ASCT at our institution between 01/01/2005 and 12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring more than one salvage line, or positron emission tomography (PET)-positive disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (n=146), busulphan/melphalan (BuMel) (n=38), gemcitabine( Gem)/BuMel (n=189) and vorinostat/Gem/BuMel (n=128). The Gem/BuMel and vorinostat/Gem/BuMel cohorts had more HRR criteria and more patients with PET-positive disease at ASCT. Treatment with brentuximab vedotin (BV) or anti-PD1 prior to ASCT, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). The median follow-up is 50 months (range, 6-186). Outcomes improved over time, with 2-year progressionfree survival (PFS)/overall survival (OS) rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016- 2019) (P<0.0001). Five-year PFS/OS rates were 72%/87% after vorinostat/ GemBuMel, 55%/75% after GemBuMel, 45%/61% after BEAM, and 39%/57% after BuMel (PFS: P=0.0003; OS: P<0.0001). These differences persisted within the PET-negative and PET-positive subgroups. Prior BV and vorinostat/GemBuMel were independent predictors of more favorable outcome, whereas primary refractory disease, ≥2 salvage lines, bulky relapse, B symptoms and PET-positivity at ASCT correlated independently with unfavorable outcomes. In conclusion, post-HDC/ASCT outcomes of patients with HRR classic Hodgkin lymphoma have improved over the last 15 years. Pre-ASCT BV treatment and optimized synergistic HDC (vorinostat/GemBuMel) were associated with this improvement.