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Summary Hodgkin lymphoma (HL) is one of the most common cancers in adolescents and young adults (AYA). Paediatric and adult therapeutic strategies diverge while sharing the common objective: maintaining optimal efficacy with less long‐term toxicity. However, few studies have compared the outcome of AYA treated according to one or the other approaches. Among the 148 patients aged 15–25 years, treated at Saint‐Louis Hospital for newly diagnosed HL between 2012 and 2018, 71 were treated according to an adult protocol and 77 were treated according to a paediatric one. The 5‐year overall survival (OS) and progression‐free survival (PFS) were, respectively, 100% and 85%, with no significant difference between treatment groups (85% in paediatric vs. 86% in adult, p = 0.7). Overall, the 5‐year PFS was 100% for early favourable stages and 78% for advanced stages. A higher risk of short‐term steroid and vincristine‐related toxicities was observed in paediatric regimen, whereas a higher risk of late toxicities was expected in adult regimen, due to higher anthracyclines, procarbazine, bleomycin and radiotherapy exposure. These results confirm the excellent outcome of AYA patients with HL, whatever the treatment strategies. They justify a tailor‐made therapeutic decision and highlight the importance of managing AYA patients in dedicated units with trained professionals. [ABSTRACT FROM AUTHOR]

The UK consensus statement on the use of plerixafor in healthy stem cell donors discusses the efficacy and safety of plerixafor in mobilizing hematopoietic progenitor cells. Studies have shown that plerixafor, in combination with G-CSF, significantly increases the efficacy of remobilization in lymphoma and myeloma patients. The use of plerixafor in allogeneic stem cell donors has been investigated, with evidence suggesting an improvement in stem cell yield and a favorable safety profile. Recommendations include using plerixafor in donors predicted to have suboptimal cell collection and reporting serious adverse reactions to relevant regulatory bodies. [Extracted from the article]

Peripheral T-cell Lymphoma (PTCL) represents a heterogenous group of aggressive non-Hodgkin Lymphomas with poor prognostic outcomes and limited treatment options. The development and refinement of therapeutic strategies for PTCL are impeded by a paucity of reliable preclinical models that accurately mimic the disease's pathophysiology. There is a dire need for more physiologically relevant models for PTCL. Here we describe a spontaneousCD8+ peripheral T-cell lymphoma cell line (LM-23) derived from a 12-week-old female Balb/cJ mouse. Both intravenous and subcutaneous administration of this cell line to syngeneic Balb/cJ mice resulted in rapid establishment of tumor growth. CHOP and anti-PD1 treatment both displayed no benefit to mice in regulating tumor growth. Such results along with its phenotypic characteristics, rapid growth, and metastatic behavior in syngeneic mice highlight its value in studying the elusive disease and discovery of novel therapeutics. [ABSTRACT FROM AUTHOR]

Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin–etoposide–doxorubicin–cyclophosphamide–vincristine–procarbazine–prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity. In this two-part retrospective, observational study, we first compared mutational landscapes in haematopoietic stem and progenitor cells (HSPCs) from patients with advanced-stage Hodgkin lymphoma in remission for at least 6 months who had been treated with eBEACOPDac (eBEACOPDac cohort), eBEACOPP (real-world eBEACOPP cohort), or doxorubicin–bleomycin–vinblastine–dacarbazine (ABVD); in buccal DNA from five children of a female patient with classical Hodgkin lymphoma treated with eBEACOPP before conceiving the third child; in sperm DNA from a patient with mild oligospermia treated with eBEACOPP; and in caecal adenocarcinoma and healthy colon tissue from a survivor of Hodgkin lymphoma treated with chlorambucil–vinblastine–procarbazine–prednisolone. For the second part, we analysed efficacy and toxicity data from adult patients (aged >16 years) treated with first-line eBEACOPDac (eBEACOPDac cohort) at 25 centres across UK, Ireland, and France; efficacy was compared with the German HD18 eBEACOPP trial data and toxicity with a UK real-world dataset. Participants in the German HD18 and UK real-world datasets were adults (aged >16 years) with previously untreated Hodgkin lymphoma, treated with first-line eBEACOPP. We had two co-primary objectives: to define the comparative stem-cell mutation burden and mutational signatures after treatment with or without procarbazine-containing chemotherapy (first study part); and to determine progression-free survival of patients with Hodgkin lymphoma treated with eBEACOPP or eBEACOPDac (second study part). Secondary objectives included overall survival and explored differences in specific toxicity outcomes, including transfusion requirements and measures of reproductive health (second study part). In the first part of the study (mutational analysis), patients treated with eBEACOPP (n=5) exhibited a higher burden of point mutations in HSPCs compared with those treated with eBEACOPDac (n=4) or ABVD (n=3; excess mutations 1150 [95% CI 934–1366] vs 290 [241–339] vs 186 [116–254]). Two novel mutational signatures, SBSA (SBS25-like) and SBSB, were identified in HSPCs and in a single neoplastic and healthy colon sample from patients who received procarbazine-containing chemotherapy. SBSB was also identified in germline DNA of three children conceived after eBEACOPP and in sperm of a male patient treated with eBEACOPP. SBSC was detected in patients treated with either ABVD or eBEACOPDac. In the second part of the study (efficacy and toxicity analysis), dacarbazine substitution did not appear to compromise efficacy or safety. 312 patients treated with eBEACOPDac (eBEACOPDac cohort; treated 2017–22, 186 [60%] male, median follow-up 36·0 months [IQR 25·2–50·1]) had a 3-year progression-free survival of 93·3% (95% CI 90·3–96·4), which was similar to the 93·3% [95% CI 92·1–94·4]) progression-free survival seen in 1945 patients in the German HD18 eBEACOPP trial (treated 2008–14, 1183 [61%] male, median follow-up 57·0 months [35·4–64·7]). Patients treated with eBEACOPDac required fewer blood transfusions (mean 1·70 units [SD 2·77] vs 3·69 units [3·89]; p<0·0001), demonstrated higher post-chemotherapy sperm concentrations (median 23·4 million per mL [IQR 11·0–632·3] vs 0·0 million per mL [0·0–0·001]; p=0·0040), and had earlier resumption of menstrual periods (mean 5·04 months [SD 3·07] vs 8·77 months [5·57]; p=0·0036) compared with 73 patients treated with eBEACOPP in the UK real-world dataset. Procarbazine induces a higher mutation burden and novel mutational signatures in patients with Hodgkin lymphoma treated with eBEACOPP and their germline DNA, raising concerns for the genomic health of survivors of Hodgkin lymphoma and hereditary consequences for their offspring. However, replacing procarbazine with dacarbazine appears to mitigate gonadal and stem-cell toxicity while maintaining similar clinical efficacy. Addenbrooke's Charitable Trust and Wellcome Trust. [ABSTRACT FROM AUTHOR]

Classic Hodgkin lymphoma (CHL) is a highly curable disease, even in advanced stages. Controversy remains over whether bone involvement negatively affects overall and progression‐free survival in patients treated with intensive chemotherapy regimens. Whether cases that present with bone lesions harbor specific tumor microenvironmental features is unknown. We investigated protein expression in diagnostic lymph node biopsies from CHL patients with and without skeletal involvement at diagnosis to identify potential markers of skeletal disease. Protein expression patterns in diagnostic formalin‐fixed paraffin‐embedded lymphoma lymph node samples from CHL patients were analyzed by nano‐liquid chromatography–tandem mass spectrometry. Patients were grouped according to skeletal involvement, which was defined as the presence of one or more FDG‐avid lesions on a diagnostic FDG‐PET/CT scan. Protein profiles identified patients with skeletal disease at diagnosis and showed disrupted cellular pathways, including immune system processes, cell adhesion, and cell growth/survival. Immunohistochemical evaluation also demonstrated differential expressions of angiotensin‐converting enzyme (ACE), intercellular adhesion molecule 3 (ICAM3), integrin alpha‐X (ITGAX), and calreticulin (CALR). In conclusion, proteomics identified altered protein expression profiles in lymph nodes among CHL cases presenting with disease disseminated to the skeletal system, which implies altered disease pathogenesis for these patients. [ABSTRACT FROM AUTHOR]

Background: Early‐phases clinical trials (Phases 1 and 2) have evolved from a traditional assessment of toxicity to an adaptive approach based on patients' medical needs and access to effective new therapies. The global risks, benefits, and relevance of early‐phases clinical trials participation for patients with hematological malignancies remain poorly evaluated. Patients and Methods: All early‐phases clinical trials participations for patients with hematological malignancies, from 2008 to 2023, in a tertiary academic center in Europe, were reviewed. Patient's demographics, tumor type categories, therapeutic responses, mortality, overall survival (OS), and investigational product (IP) were assessed. Results: Over the period 2008–2023, 736 patients participating in 92 different early‐phases clinical trials, were analyzed. The most common tumor categories were diffuse large B‐cell lymphoma (n = 253; 34.4%), acute myeloid leukemia/myelodysplastic syndrome (n = 164; 22.3%) and multiple myeloma (n = 100; 13.6%). The median OS was 14.8 (95% CI: 12.4–17.9) months and response rate 31.9%, including complete responses in 13.5% of patients. By tumor categories, the highest and lowest median duration of OS were observed for patients with Hodgkin lymphoma (99.8; [95% CI: 47.0‐not reached] months) and peripheral T‐cell lymphoma (8.9 [95% CI: 5.3–12.0] months), respectively. The on‐protocol and treatment‐related mortality rates were 5.43% and 0.54%, respectively. Overall response rate was 29.1% including 13.5% of complete response. Overall, 202 (27.5%) patients received an IP later approved by the health authorities, and those patients had better OS (18.2 months vs. 12.1 months HR: 1.160 [95% CI; 0.6977–1.391], p = 0.0283). Conclusion: In conclusion, patients with hematologic malignancies who have participated in early‐phases clinical trials over the past 15 years have achieved variable therapeutic response rates, acceptable risk/benefit ratio and potentially significant therapeutic advantages. This study provides framework material for hematologists to further discuss clinical trial participation with their patients. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are now considered revolutionary agents in the treatment of various cancers. Prospective data are limited on the patterns of usage and toxicity profile of these drugs. We planned this study for addressing the same in Indian patients. This prospective study was conducted over a period of 2 years. All patients who were treated with Nivolumab, pembrolizumab, atezolizumab, and durvalumab were included. Immune-related adverse events were recorded. Toxicities were graded and number of patients experiencing dose limiting toxicities was recorded. A total of 53 patients received one of the above four agents. Majority of patients were less than 60 years of age. Carcinoma lung was the most frequent malignancy followed by renal cell carcinoma, Hodgkin's Lymphoma, Urinary Bladder cancers, Malignant Melanoma, and Recurrent/Metastatic Head and neck cancer. Nivolumab was used in most of the study population followed by pembrolizumab. Majority of agents were used in second line. The frequency of all grade adverse events for fatigue, anemia, pneumonitis, skin rash, dyspnea, diarrhea, and hypothyroidism were (in %) 73.58, 62.26, 16.9, 11.32, 9.43, 9.43, and 7.55, respectively. No grade 5 toxicity was observed. None of the grade 3 or 4 toxicities led to treatment discontinuation. Statistically, no difference was found for all grade toxicities among ICI drugs and among the various lines of use. Nivolumab was the commonest drug used in our cohort. Most of ICIs were used in second-line setting. Toxicities are in line with the published literature. [ABSTRACT FROM AUTHOR]

Primary uterine non-Hodgkin lymphoma (NHL) is rarely reported, as its incidence is extremely low. We describe a 72 year old patient with primary uterine non-Hodgkin's lymphoma stage IV, diffuse B-cell large cells, who responded well to cytotoxic chemotherapy (R-CHOP). Radiological investigations exhibited certain characteristics, including magnetic resonance T2 weighted imaging, enhanced scanning, diffusion weighted imaging and apparent diffusion coefficient values. The lesion in the anterior wall of the uterine body was relatively large, with a size of about 34mm×47mm×43mm. The gold standard for diagnosis is still the pathological examination of a biopsy specimen, which revealed diffuse large cell of B lineage. This article reviews data collected from 141 patients in the literature. [ABSTRACT FROM AUTHOR]

AbstractNodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for ≈5% of all Hodgkin lymphoma (HL) cases. As some characteristics of NLPHL resemble B-cell non-Hodgkin lymphoma (B-NHL), nodular lymphocyte-predominant B-cell lymphoma has been proposed as alternative name. Unlike classical HL (cHL), NLPHL is mostly diagnosed in early stages. The clinical course is usually indolent. Overall, NLPHL patients have an excellent prognosis and the majority experiences long-term survival. Except for stage IA disease which is sufficiently treated with radiotherapy alone, treatment of newly diagnosed NLPHL is often very similar to cHL. However, activity has also been demonstrated for rituximab-containing protocols applied in B-NHL. Second-line treatment is chosen individually and mostly less intensive than in cHL. Chimeric antigen receptor T-cell therapy and bispecific antibodies may be part of future treatment strategies for NLPHL. This review aims at summarizing recent data on treatment approaches and discussing future perspectives in NLPHL. [ABSTRACT FROM AUTHOR]

Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4+ T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL. Compared with non-responders, responding patients have more circulating CD4+ naïve and central memory T cells and B cells, as well as more diverse CD4+ T cell and B cell receptor repertoires. Importantly, a population of circulating and tumor-infiltrating IL1β+ monocytes/macrophages is detectable in patients with cHL but not healthy donors, and a proinflammatory, tumor-promoting signature of these circulating IL1β+ monocytes is associated with resistance to PD-1 blockade in cHL. Altogether, our findings reveal extensive immune rewiring and complementary roles of CD4+ T cells, B cells and IL1β+ monocytes in the response to PD-1 blockade and suggest that these features can be captured with a peripheral blood test. Patients with classic Hodgkin lymphoma (cHL) respond well to PD-1 blockade, but the underlying cellular insights are still lacking. Here, the authors use single-cell transcriptome and spatial analyses to identify distinct circulating and tumor-infiltrating CD4+ T cell, B cell and IL1β+ monocyte/macrophage features associated with response to PD-1 blockade in cHL. [ABSTRACT FROM AUTHOR]

Background: Cancer is a major cause of mortality worldwide, and differences in cancer mortality rates between countries are, in part, due to differences in access to cancer care, including medicines. National essential medicines lists (NEMLs) play a role in prioritization of healthcare expenditure and access to medicines. We examined the association between amenable cancer mortality and listing medicines used in the management of eight cancers (non-melanoma skin, uterine, breast, Hodgkin lymphoma, colon, leukemia, cervical, and testicular) in national essential medicines lists of 158 countries and summarized changes to the inclusion of cancer treatments in NEMLs. Methods: We conducted a cross-sectional examination of NEMLs for 158 countries, which were obtained in May 2023. We identified medicines used to treat each of the eight cancers and determined the number of medicines listed by NEMLs for each cancer. We conducted multiple linear regressions to examine the association between the number of medicines listed on the NEMLs and cancer mortality. Results: We found associations between cancer medicine listing and outcomes for six of the eight examined cancers (non-melanoma skin cancer (p = 0.001), uterine cancer (p = 0.006), breast cancer (p = 0.001), Hodgkin lymphoma (p = 0.021), colon cancer (p = 0.006), and leukemia (p = 0.002)), when adjusting for healthcare expenditure and population size. Conclusion: There was an association between listing cancer medicines on NEMLs and cancer mortality. Further research is required to explore how cancer mortality may be impacted by other cancer interventions, as well as policies to improve equitable access to cancer care. [ABSTRACT FROM AUTHOR]

AbstractDespite increasing utilization of CAR T-cell therapy, data are lacking regarding long term follow up and risk of infectious complications after the early period following CAR T-cell infusion. In this study, we sought to compare epidemiology and risk factors for early (≤ 3 months) and late (3 months to 1 year) infections. Data were retrospectively collected at six time points: pre-CAR T, day of infusion, and at 3, 6, 9, and 12 months post CAR-T infusion for all consecutive adult patients treated at our institution. In this cohort, the cumulative incidence of any infection was 73.2% in the first year. Bridging therapy, CRS, neurotoxicity and steroid use were identified as contributing risk factors for early bacterial infections. After 3 months, community acquired respiratory infections were common. We characterize bacterial, viral and fungal pathogens based on time elapsed after CAR T-cell infusion. [ABSTRACT FROM AUTHOR]

As the integration of novel agents in the frontline therapy has primarily impacted upfront therapy of advanced stage classic Hodgkin lymphoma (cHL), this review will outline current management of advanced stage cHL at first line and at progression and relapse, focusing on the biology, clinical features, and therapeutic approaches. Due to S1826, HD21, and ECHELON-1, the first-line treatment of advanced cHL has dramatically changed, with novel agents part of standard frontline therapy. BV-AVD, BrECADD, and Nivo-AVD are now standard first-line regimens for patients with stage III-IV cHL, with improved outcomes compared to historical data in cHL. The addition of BV and PD-1 inhibitors to relapsed/refractory (r/r) cHL chemotherapy regimens improved outcomes in this population. Now, there is a paradigm shift with PD-1 moving into frontline therapy, so new studies to evaluate the role of these novel agents in salvage will be required to determine the optimal salvage approach in r/r cHL. [ABSTRACT FROM AUTHOR]

Predictive prognostic scoring (PS) systems are not primarily applicable to elderly patients with classical Hodgkin lymphoma (cHL). The objective of this study was to develop a PS system for these patients. The derivation cohort (DC) was utilized for model development, consisting of 97 variables. The resulting algorithm was named as Hodgkin's Lymphoma Early Death in the Elderly within 12 months (HEDEL12). Internal and external validation cohorts (IVC and EVC) were employed for validation. A total of 286 patients were evaluated retrospectively. In DC 38 of 178 patients died within the first 12 months and overall survival (OS) at 12-month was 78.6%. Independent predictors of HEDEL12 were female sex, low albumin levels (<3.5 g/dL), and ECOG scores 2-4. According to HEDEL12 scores 0–1, OS at 12- months were 89.8% and 91.0% for IVC and EVC, respectively. The HEDEL12 scoring is useful in predicting the survival of advanced-stage cHL patients. KEY POINTS: Predictive prognostic scoring (PS) systems are not applicable to elderly patients with classical Hodgkin lymphoma Female sex, low albumin levels (<3.5 g/dL), and ECOG scores 2-4 are independent predictors of survival in older advanced stage cHL patients. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma variant of Richter syndrome (HL-type RS) is a very rare disease, in which chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) is transformed into novel Hodgkin lymphoma. The most important prognostic factor of HL-type RS is the clonal relationship between HL-type RS and the preexisting CLL/SLL. Detailed confirmation of clonally unrelated HL-type RS cases have not been reported. To the best of our knowledge, this is the first case of HL-type RS confirmed as clone independent by a detailed comparison of immunoglobulin gene rearrangement clones and gene mutations. A 76-year-old man, diagnosed with SLL 1 year before transformation was treated with Zanubrutinib 3 months before transformation. When diagnosed with HL-type RS, he presented with symptoms of hemophagocytic syndrome. Positive therapeutic effects were achieved using a modified rituximab-doxorubicin, bleomycin, vinblastine, dacarbazine regimen in combination with Zanubrutinib. We also discuss a thorough review of the relevant literature we performed to help us better understand this rare disease. [ABSTRACT FROM AUTHOR]

Membrane proteins, especially extracellular domains, are key therapeutic targets due to their role in cell communication and associations. Yet, their functions and interactions often remain unclear. This study presents a general method to discover interactions of membrane proteins with immune cells and subsequently to deorphanize their respective receptors. We developed a comprehensive recombinant protein library of extracellular domains of human transmembrane proteins and proteins found in the ER-Golgi-lysosomal systems. Using this library, we conducted a flow-cytometric screen that identified several cell surface binding events, including an interaction between carbonic anhydrase 9 (CAH9/CA9/CAIX) and CD14high cells. Further analysis revealed this interaction was indirect and mediated via platelets bound to the monocytes. CA9, best known for its diverse roles in cancer, is a promising therapeutic target. We utilized our library to develop an AlphaLISA high-throughput screening assay, identifying CLEC2 as one robust CA9 binding partner. A five-amino-acid sequence (EDLPT) in CA9, identical to a CLEC2 binding domain in Podoplanin (PDPN), was found to be essential for this interaction. Like PDPN, CA9-induced CLEC2 signaling is mediated via Syk. A Hodgkin's lymphoma cell line (HDLM-2) endogenously expressing CA9 can activate Syk-dependent CLEC2 signaling, providing enticing evidence for a novel function of CA9 in hematological cancers. In conclusion, we identified numerous interactions with monocytes and platelets and validated one, CA9, as an endogenous CLEC2 ligand. We provide a new list of other putative CA9 interaction partners and uncovered CA9-induced CLEC2 activation, providing new insights for CA9-based therapeutic strategies. [ABSTRACT FROM AUTHOR]

The article discusses the use of pembrolizumab as a salvage treatment for T‐cell/histiocyte‐rich large B‐cell lymphoma (TCRLBCL) and Epstein–Barr virus (EBV)‐positive large B‐cell lymphoma. The study evaluated the efficacy of pembrolizumab in seven patients with these lymphomas who had relapsed or were refractory to standard chemo‐immunotherapy. Results showed that 71% of patients achieved a complete remission with pembrolizumab, with limited treatment toxicities. The study suggests that checkpoint inhibitors like pembrolizumab may be a potential therapeutic alternative for patients who do not benefit from CAR T‐cell therapy. [Extracted from the article]

The article discusses Merkel cell carcinoma (MCC) in solid organ transplant recipients (SOTRs), highlighting the increased incidence of MCC in this population. The study provides a systematic synthesis of current literature on the clinical characteristics, treatments, and outcomes of MCC in SOTRs, with a focus on male patients of European ancestry. The research suggests that factors such as immunosuppressive medications and Merkel cell polyomavirus (MCPyV) status may contribute to the risk of SOTR-MCC. Treatment for SOTR-MCC aligns with that of the general population, with surgery being the most common approach, although PD-1/PD-L1 immune checkpoint inhibitors have shown promise in improving overall survival for metastatic MCC patients. [Extracted from the article]

The aim of the present study was to evaluate the occurrence of synchronous or metachronous hematologic and gynecologic malignancies. The medical database of the pathology department at a tertiary center was searched from 2016 to 2024 for cases involving both hematologic and gynecologic tumors. A literature search using Google Scholar and PubMed was also conducted between May and June 2024. Articles reporting surgical pathology data were included, while radiologic studies and those lacking pathology data were excluded. Cases involving one gynecologic cancer and one hematologic malignancy were analyzed. Three cases from our center and 25 cases from 15 English‐language articles were identified. The mean age of the cases at diagnosis was 61.4 ± 9.4 years. A total of 19 patients (68%) were diagnosed with synchronous cancers, while the rest had metachronous diagnoses. Endometrial cancer was seen in 20 cases (71.4%): 14 synchronous and five metachronous endometrioid adenocarcinomas, and one unspecified metachronous endometrial cancer. This was followed by five cases of ovarian cancer (17.9%): three synchronous serous ovarian carcinomas, one metachronous serous ovarian carcinoma, and one synchronous ovarian adenocarcinoma. Additionally, there were two cases of cervical cancer (7.1%): one synchronous adenosquamous carcinoma and one metachronous invasive squamous carcinoma, and one case of carcinosarcoma (3.6%). Involvement of more than one site is possible for hematolymphoid cancer, commonly affecting the pelvic or para‐aortic lymph nodes in 16 patients (57.1%), with other sites including the cervix (4 cases, 14.3%), ovary (4 cases, 14.3%), uterus (2 cases, 7.1%), iliac/inguinal lymph nodes (2 cases, 7.1%), fallopian tube (1 case, 3.6%), vagina (1 case, 3.6%), liver (1 case, 3.6%), abdomen (1 case, 3.6%), and appendix (1 case, 3.6%). Two cases were unspecified. Non‐Hodgkin lymphoma (NHL), primarily of B cell lineage, was the most common hematologic malignancy (25 cases, 89.3%, with 22 cases being B cell lineage). In contrast, Hodgkin lymphoma was observed in two cases (7.1%), and acute leukemia in one case (3.6%). Among 21 patients with available follow‐up data, eight died during the follow‐up period. The co‐occurrence of NHL, Hodgkin lymphoma, and acute leukemia with gynecologic cancers is rare. However, during surgery for gynecologic cancers, the potential of synchronous lymphoma should be considered, particularly in cases with unusual retroperitoneal lymphadenopathy. [ABSTRACT FROM AUTHOR]

Abstract\nKEY POINTSAdvances in treating classic Hodgkin lymphoma (cHL) have improved cure rates, with overall survival exceeding 80%, resulting in a growing population of survivors at risk of long-term complications, particularly cardiac and pulmonary toxicity. Bleomycin, a key component of combination chemotherapy, is associated with bleomycin-induced pulmonary toxicity (BPT). Using label-free quantification nano liquid chromatography-tandem mass spectrometry, protein expression in diagnostic lymphoma samples from patients with and without BPT was compared. Results showed differential protein expression and disrupted cellular pathways, suggesting biological differences in BPT risk. Immunohistochemical analysis revealed higher expression of JAK3, BID, and MMP9, and lower expression of CD20, TPD52, and PIK3R4 in patients with BPT. High BID and low CD20 expression were associated with inferior overall survival, while high BID and low JAK3 and CD20 expression were linked to poorer progression-free survival. These findings highlight altered protein profiles in pretreatment cHL biopsies associated with BPT development.Proteomics reveals distinct protein profiles in the diagnostic lymph node biopsies of cHL patients prone to bleomycin-induced pulmonary toxicity.Protein expression of CD20, TPD52, JAK3, BID, MMP9, and PIK3R4 correlates with development of bleomycin-induced pulmonary toxicity. [ABSTRACT FROM AUTHOR]

Background and Clinical Significance: Since their first introduction in the early 1950s, hip prostheses implants are becoming increasingly reliable; nevertheless, failures can still happen. The focus of this paper is to present a case study on a catastrophic fractured hip prosthesis liner that consequently led to revision surgery and the replacement of the destroyed implant. Case Presentation: The patient was diagnosed with Hodgkin's lymphoma and had Total Hip Arthroplasty on both legs, but only the right side needed revision due to a fracture in the liner. The patient's symptoms were a squeaking sound, functional impairment, and pain, and an X-ray showed the extent of the damage. We also present a short review on the mechanisms of liner fracture, focusing strictly on the mechanical aspects of failure. Conclusions: Hip prosthesis implants are not immune to failure. This case highlights the importance of an interdisciplinary approach and emphasizes the need for vigilant postoperative monitoring and the development of predictive tools. [ABSTRACT FROM AUTHOR]

The clinicopathologic spectrum of nodular lymphocyte-predominant Hodgkin lymphoma, now termed "nodular lymphocyte-predominant B-cell lymphoma" (NLPBCL), may include incipient, typical and transformed forms. On the basis of its clinicopathologic spectrum, NLPBCL is very similar to follicular lymphoma not associated with BCL2 translocation. In addition, NLPBCL, based on biopathologic features (gene profiling signature, and phenotypic and morphotypic characteristics), is a germinal center-derived B-cell neoplasm; therefore, it could be included in the follicular lymphoma group of non-Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

Epstein–Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), which are the only members of the gamma(γ) herpesviruses, are oncogenic viruses that significantly contribute to the development of various human cancers, such as Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, Kaposi's sarcoma, and primary effusion lymphoma. Oncogenesis triggered by γ-herpesviruses involves complex interactions between viral genetics, host cellular mechanisms, and immune evasion strategies. At the genetic level, crucial viral oncogenes participate in the disruption of cell signaling, leading to uncontrolled proliferation and inhibition of apoptosis. These viral proteins can modulate several cellular pathways, including the NF-κB and JAK/STAT pathways, which play essential roles in cell survival and inflammation. Epigenetic modifications further contribute to EBV- and KSHV-mediated cancerogenesis. Both EBV and KSHV manipulate host cell DNA methylation, histone modification, and chromatin remodeling, the interplay of which contribute to the elevation of oncogene expression and the silencing of the tumor suppressor genes. Immune factors also play a pivotal role in the development of cancer. The γ-herpesviruses have evolved intricate immune evasion strategies, including the manipulation of the major histocompatibility complex (MHC) and the release of cytokines, allowing infected cells to evade immune detection and destruction. In addition, a compromised immune system, such as in HIV/AIDS patients, significantly increases the risk of cancers associated with EBV and KSHV. This review aims to provide a comprehensive overview of the genetic, epigenetic, and immune mechanisms by which γ-herpesviruses drive cancerogenesis, highlighting key molecular pathways and potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Introduction: Ovarian tissue cryopreservation (OTC) is recommended by scientific societies for women undergoing highly gonadotoxic cancer treatments. Following transplantation, the restoration of ovarian function is typically characterised by the resumption of spontaneous menstruation. Yet, a few studies have looked at the longitudinal hormonal variations following transplantation. This study aims to investigate the fluctuation of gonadotropins and granulosa/theca cells secretions during the interval between ovarian transplantation and the recovery of menstrual function in two young women with no residual ovarian activity. Method: We selected two patients diagnosed with Hodgkin's lymphoma, initially referred for OTC at the ages of 19 and 15, respectively, and who had both undergone two consecutive stem cell transplants due to recurrent disease episodes. Both patients presented with premature ovarian failure and returned at ages 29 and 26, respectively, for ovarian cortex transplantation. Hormonal secretions and menstrual function were closely monitored both prior and in the months following the ovarian transplantation. Results: Menstruation resumed at 7 and 5 months post-transplantation, respectively. FSH and LH levels significantly decreased as early as 1 and 3 months before the first menstruation. As for ovarian hormonal secretion, AMH, measured with an ultra-sensitive assay ("pico AMH"), and Inhibin B were the first to increase, starting 1 month before the resumption of menstruation. Subsequently, AMH levels consistently remained very low throughout the follow-up, as did androgens, which showed a slight increase after the graft but remained at postmenopausal levels. Conclusion: Pico AMH, measured by an ultra-sensitive assay, Inhibin B and estradiol are the first ovarian hormones to be secreted following an ovarian graft, with levels rising 1 month prior the return of menstruation. However, the earliest hormonal indicators of graft success are the significant drops in FSH and LH levels, accompanied by a rise in estradiol levels, which occur 1–3 months before menstruation resumes. [ABSTRACT FROM AUTHOR]

We aimed to study the possible factors influencing visualisation of brown adipose tissue (BAT) on FDG PET/CT at diagnosis in children. A total of 92 children or adolescents were included (63 patients with Hodgkin lymphoma (HL) and 29 patients with sarcoma). We examined FDG PET/CT images obtained at diagnosis and searched for FDG uptake in BAT. We analysed the relationship between BAT activation and different possible influencing factors, such as age, sex, outside temperature or season, histological type of malignancy (HL or sarcoma), and volumetric and metabolic values of the tumour tissue. Mann-Whitney, Chi-2 and Fischer's exact tests, and logistic regression analysis were used. We found no significant difference in the BAT activation frequency between patients with HL and those with sarcoma (P = 0.12). BAT visualization on FDG PET/CT in the HL subgroup showed a trend towards lower TMTV (P = 0.06) and TLG (P = 0.09). The logistic regression analysis did not show a significant correlation between BAT visualisation on FDG PET/CT and TMTV values. In terms of age, we found a slightly significant correlation for the whole group (P = 0.06) and for the subgroup of HL patients (P = 0.04) in logistic regression. In terms of seasons, the majority (45%) of BAT positive cases were found in autumn. BAT visualisation may be associated with a low HL tumour mass. Multivariate analysis revealed a correlation between BAT activation and age in paediatric patients. BAT visualisation do not differ between boys and girls. [ABSTRACT FROM AUTHOR]

Simple Summary: This study looks at the risk of developing breast cancer in survivors of Hodgkin lymphoma (HL), especially those who received chest radiation as part of their treatment. HL survivors are at a higher risk of breast cancer, and this risk increases over time. The research shows that radiation therapy used to treat HL can cause long-term damage to breast tissue, leading to an increased chance of developing cancer later on. The study also found that early screening and continuous monitoring are important for detecting cancer early in these survivors. Overall, it highlights the need for special care and surveillance for people who survived Hodgkin lymphoma, especially if they had been subjected to chest radiation. Hodgkin lymphoma (HL) treatment has dramatically improved, with high survival rates in early stages. However, long-term survivors face an increased risk of secondary cancers, particularly breast cancer (BC), which emerge as a leading cause of mortality decades after therapy. Background/Objectives: This study explores the risk of BC and the toxic effects of radiation therapy (RT) in long-term HL survivors compared to age-matched high-risk women, including BRCA1 and BRCA2 mutation carriers. A prospective study was conducted on 62 women who had undergone chemotherapy and involved-field RT for HL, with MRI used to assess breast tissue changes. This study's primary endpoint was to analyze BC incidence in HL survivors, while secondary objectives focused on the analysis of background parenchymal enhancement (BPE) in irradiated areas. Results: The findings revealed a 5% incidence of BC in HL survivors, with 50% showing moderate or marked BPE, similar to that observed in high-risk BC controls. No significant differences in BPE distribution were found between the two groups. Conclusions: The study highlights the long-term risk of BC in HL survivors and suggests that advanced RT techniques and targeted therapies may help reduce the incidence of secondary tumors. Future research should focus on understanding the genetic and biological mechanisms behind treatment-induced cancers [ABSTRACT FROM AUTHOR]

Simple Summary: The tumor necrosis factor (TNF) family plays a crucial role in the pathogenesis of Hodgkin lymphoma. Hodgkin Reed–Sternberg cells, the diagnostic hallmark of the disease, exhibit overexpression of TNF receptor family members such as CD30 and CD40. These molecules have a critical roles in the survival and proliferation of Hodgkin Reed–Sternberg cells. Therefore, targeting these TNF receptors represents a promising therapeutic strategy. Therapies that target CD30 have already shown efficacy in clinical settings. Checkpoint inhibitors such as nivolumab and pembrolizumab have demonstrated high response rates in patients with classic Hodgkin lymphoma, particularly in those who have not responded to conventional therapies. By understanding how TNF signaling interacts with immune checkpoints, researchers can design more effective treatment regimens that simultaneously target multiple pathways. The tumor necrosis factor (TNF) family, which includes 19 ligands and 29 receptors, influences cellular proliferation, differentiation, and apoptosis. The TNF family plays a crucial role in the pathogenesis of Hodgkin lymphoma (HL), particularly through its influence on the tumor microenvironment (TME). Hodgkin Reed–Sternberg (HRS) cells, the hallmark of classic HL (cHL), exhibit overexpression of TNF receptor family members such as CD30 and CD40. Given the critical roles of CD30 and CD40 in the survival and proliferation of HRS cells within the TME, targeting these TNF receptors represents a promising therapeutic strategy; therapies that target CD30 have already shown efficacy in clinical settings. The programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis plays a crucial role in immune evasion by HRS cells, which express PD-L1 that interacts with PD-1 on T cells, leading to T cell exhaustion and a diminished immune response against the tumor. By blocking this interaction, checkpoint inhibitors such as nivolumab and pembrolizumab have demonstrated high response rates in patients with cHL, particularly in those who have not responded to conventional therapies. The integration of immune checkpoint inhibitors (ICIs) with standard chemotherapy regimens has improved outcomes for patients with advanced-stage cHL. By understanding how TNF signaling interacts with immune checkpoints, researchers can design more effective treatment regimens that simultaneously target multiple pathways. Combining TNF inhibitors with checkpoint blockade therapies may enhance the overall anti-tumor response by addressing both direct tumor signaling and the immune evasion mechanisms employed by tumor cells. [ABSTRACT FROM AUTHOR]

Objective: B-HOLISTIC was a real-world retrospective study of treatment patterns and clinical outcomes in Hodgkin lymphoma (HL) in regions outside Europe and North America. This subgroup analysis reports findings from Saudi Arabia, Türkiye, and South Africa. Materials and Methods: Patients aged ≥18 years and diagnosed with stage IIB-IV classical HL receiving frontline chemotherapy (frontline cHL) and/or with relapsed/refractory HL (RRHL) from January 2010 to December 2013 were assessed. The primary endpoint was progression-free survival (PFS) in patients with RRHL. Results: Overall, 694 patients (RRHL: n=178; frontline cHL: n=653) were enrolled. Among patients with RRHL, >80% received first salvage chemotherapy. The most common first salvage regimens were etoposide, methylprednisolone, cytarabine, and cisplatin in Saudi Arabia (78.3%) and dexamethasone, cytarabine, and cisplatin in Türkiye (36.1%) and South Africa (40%). Median PFS (95% confidence interval [CI]) in the RRHL group was 5.1 (3.0-15.9), 19.7 (7.5-not reached), and 5.2 (1.1-10.1) months in Saudi Arabia, Türkiye, and South Africa, respectively. The 5-year PFS and overall survival (95% CI) rates in patients with RRHL were 33.2% (21.6-45.2) and 78.2% (65.9-86.5) in Saudi Arabia, 42.5% (29.5-54.9) and 79.4% (67.2-87.5) in Türkiye, and 13.1% (4.2-27.0) and 53% (35.5-67.8) in South Africa, respectively. Conclusion: This study showed that the clinical outcomes in Türkiye and Saudi Arabia were generally comparable with those of Western countries during the study period, although Saudi Arabia had lower PFS rates. Conversely, the clinical outcomes in South Africa were suboptimal, emphasizing the need for novel therapies and improved progression to stem cell transplantation. These data may serve as a control group for future studies in these countries and inform clinical decision-making. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma (HL) is primarily a nodal disease. Cutaneous involvement of HL as a presenting feature is extremely rare. Skin involvement is usually seen as a metachronous involvement in the course of disease and is associated with poor prognosis. Primary skin and soft tissue involvement can be construed as nonhematological, inflammatory, or infective etiology. We report a 14-year-old girl with fever, weight loss, lymphadenopathy, and multiple papular lesions over the right chest wall as initial manifestation of HL, posing a diagnostic challenge. In view of stage IVBE, patient was managed with intensive chemotherapy regimen and is currently free of disease at 6 months of follow-up. [ABSTRACT FROM AUTHOR]

Purpose:In vitro maturation (IVM) of oocytes obtained from ovarian tissue during ovarian tissue cryopreservation (OTC) is a technique for fertility preservation in patients with cancer obviating the need to postpone chemotherapy initiation. Little is known about IVM outcomes in hematological malignancies, especially post-chemotherapy. The purpose of this study was to evaluate the effect of cytotoxic treatment on the potential to retrieve immature oocytes and mature them in vitro and examine the association between serum inflammatory markers and these results. Methods: In this retrospective study, we evaluated inflammation markers, including B symptoms and IVM outcomes of 78 chemotherapy-naive and exposed patients diagnosed with Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), or acute myeloid leukemia (AML). Results: The mean number of oocytes found was 7.2 ± 7.2. The average number of oocytes matured by IVM was 2.8 ± 3.5, and a mean IVM rate was 32.1 ± 27.7%. All patients in the ALL and AML groups had previous exposure to chemotherapy before OTC, compared with 50.0% (7/14) and 31.9% (15/47) in the NHL and HL groups, respectively. Among patients with lymphoma, chemotherapy exposure was associated with the reduced number of retrieved oocytes (9.8 ± 7.7 vs. 5.3 ± 5.7 oocytes, p = 0.049) in the HL group but not with the number of mature oocytes or IVM rate. B symptoms were not associated with IVM outcomes. Lymphocyte count (ß = 1.584; p = 0.038) and lactate dehydrogenase (ß = 0.009; p = 0.043) were the only significant parameters associated with the number of matured oocytes in a linear regression model. Conclusion: IVM is a promising assisted reproductive technology, which holds great potential for patients in need of urgent fertility preservation or those who cannot receive hormonal stimulation. Our results demonstrate the feasibility of the technique even in the presence of B symptoms and elevated inflammation markers and in patients with previous exposure to chemotherapy. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICI) are increasingly used in combination. To understand the effects of different ICI categories, we characterized changes in circulating autoantibodies in patients enrolled in the E4412 trial (NCT01896999) of brentuximab vedotin (BV) plus ipilimumab, BV plus nivolumab, or BV plus ipilimumab-nivolumab for Hodgkin Lymphoma. Cycle 2 Day 1 (C2D1) autoantibody levels were compared to pre-treatment baseline. Across 112 autoantibodies tested, we generally observed increases in ipilimumab-containing regimens, with decreases noted in the nivolumab arm. Among 15 autoantibodies with significant changes at C2D1, all nivolumab cases exhibited decreases, with more than 90% of ipilimumab-exposed cases showing increases. Autoantibody profiles also showed differences according to immune-related adverse event (irAE) type, with rash generally featuring increases and liver toxicity demonstrating decreases. We conclude that dynamic autoantibody profiles may differ according to ICI category and irAE type. These findings may have relevance to clinical monitoring and irAE treatment. [ABSTRACT FROM AUTHOR]

A 68-year-old woman presented with worsening dyspnea. She had presented to her local community hospital 10 days earlier with similar symptoms. She was diagnosed with a right-sided pleural effusion, which was attributed to pneumonia and treated with antibiotics. She underwent two thoracenteses within a week, with relief of dyspnea after each procedure. Two days after hospital discharge, she developed recurrence of dyspnea and presented to our hospital. She denied any cough, fever, chills, or night sweats. She denied leg swelling, orthopnea, or paroxysmal nocturnal dyspnea. She did not have any recent surgeries or trauma. She had a medical history notable for Hodgkin lymphoma treated with radiation 40 years ago, renal cancer treated with nephrectomy, COPD on chronic 2 L oxygen nasal cannula, and pulmonary embolism on chronic anticoagulation. She also had a chronic left-sided chest port, which had been placed for a long-standing history of difficult IV access. [ABSTRACT FROM AUTHOR]

Combined modality treatment with chemotherapy followed by consolidation radiation therapy (RT) provides excellent outcomes for patients with early-stage Hodgkin lymphoma. The international standard of care for consolidation RT, involved-site/involved-node radiation therapy (ISRT/INRT), has never been evaluated in a randomized phase 3 trial against the former standard involved-field radiation therapy (IFRT). In the multicenter phase 3 GHSG (German Hodgkin Study Group) HD17 trial, patients with early-stage unfavorable Hodgkin lymphoma were randomized between the standard Combined modality treatment group and a positron-emission tomography (PET)-guided group. In the standard group, patients received 2 cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) and 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy IFRT. In the experimental group, patients received no further therapy if postchemotherapy PET was negative and 30 Gy GHSG INRT, comparable to and therefore termed here ISRT, if PET was positive. Here, we analyze the interim PET-positive patients in a post hoc analysis, and therefore the randomized comparison of IFRT versus INRT/ISRT. A total of 1100 patients were randomized, of which 311 had a positive PET after chemotherapy. Kaplan-Meier estimates of 4-year progression-free survival were 96.8% (95% CI, 91.6%-98.8%) in the IFRT group and 95.4% (95% CI, 89.9%-97.9%; HR, 1.40; 95% CI, 0.44-4.42) in the ISRT group. The pattern of recurrence analyses indicated that none of the cases of disease progression or recurrence in the ISRT group would have been prevented by the use of IFRT. Acute grade 3/4 toxicities occurred in 8.5% of IFRT patients and 2.6% of ISRT patients (P =.03). For the first time, consolidation INRT/ISRT was randomly compared with IFRT in a phase 3 trial. Regarding progression-free survival, no advantage of IFRT could be demonstrated. In summary, our data confirm the status of INRT/ISRT as the current standard of care. [ABSTRACT FROM AUTHOR]

PURPOSE: Patients diagnosed with advanced-stage Hodgkin lymphoma (aHL) have historically been risk-stratified using the International Prognostic Score (IPS). This study investigated if a machine learning (ML) approach could outperform existing models when it comes to predicting overall survival (OS) and progression-free survival (PFS). PATIENTS AND METHODS: This study used patient data from the Danish National Lymphoma Register for model development (development cohort). The ML model was developed using stacking, which combines several predictive survival models (Cox proportional hazard, flexible parametric model, IPS, principal component, penalized regression) into a single model, and was compared with two versions of IPS (IPS-3 and IPS-7) and the newly developed aHL international prognostic index (A-HIPI). Internal model validation was performed using nested cross-validation, and external validation was performed using patient data from the Swedish Lymphoma Register and Cancer Registry of Norway (validation cohort). RESULTS: In total, 707 and 760 patients with aHL were included in the development and validation cohorts, respectively. Examining model performance for OS in the development cohort, the concordance index (C-index) for the ML model, IPS-7, IPS-3, and A-HIPI was found to be 0.789, 0.608, 0.650, and 0.768, respectively. The corresponding estimates in the validation cohort were 0.749, 0.700, 0.663, and 0.741. For PFS, the ML model achieved the highest C-index in both cohorts (0.665 in the development cohort and 0.691 in the validation cohort). The time-varying AUCs for both the ML model and the A-HIPI were consistently higher in both cohorts compared with the IPS models within the first 5 years after diagnosis. CONCLUSION: The new prognostic model for aHL on the basis of ML techniques demonstrated a substantial improvement compared with the IPS models, but yielded a limited improvement in predictive performance compared with the A-HIPI. Machine-Learning based advanced-stage Hodgkin lymphoma (aHL) prognosis surpasses International Prognostic Score, competes with aHL international prognostic index in overall survival and progression-free survival prediction. [ABSTRACT FROM AUTHOR]

Classical Hodgkin Lymphoma (CHL) is a rare malignant neoplasm of the lymphatic system. While CHL typically responds well to conventional treatments, some cases may experience relapse to other subtypes, with the development of secondary peripheral T-cell lymphoma (PTCL) being relatively uncommon. Herein, we report a rare case of nodal T follicular helper cell lymphomas,nos (nTFHL-NOS) secondary to CHL, accompanied by aberrant CD20 expression and clonal rearrangements of T-cell receptor (TCR) and immunoglobulin (IG). A 74-year-old male, was diagnosed with CHL, leaning toward the mixed cell type, 6 years ago. He received six cycles of the Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD) regimen, achieving complete clinical remission. The patient was admitted to our hospital due to the appearance of multiple skin nodules 66 months later. Histopathological analysis revealed nTFHL-NOS, with aberrant CD20 expression and clonal rearrangements of TCR and IG. The patient underwent two cycles of chemotherapy with brentuximab vedotin and the Gemcitabine-Oxaliplatin (G-mox) regimen, resulting in a reduction of the skin lesions to 2 cm × 1 cm. We discuss this rare case and review related literature. [ABSTRACT FROM AUTHOR]

Aim: The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). This systematic review and meta-analysis aimed to determine the ability of G-CSF+plerixafor to mobilize peripheral blood (PB) CD34+ cells and examine its safety profile. Methods: We performed a database search using the terms 'granulocyte colony stimulating factor', 'G-CSF', 'AMD3100', and 'plerixafor', published up to May 1, 2023. The methodology is described in further detail in the PROSPERO database (CRD42023425760). Results: Twenty-three studies were included in this systematic review and meta-analysis. G-CSF+plerixafor resulted in more patients achieving the predetermined apheresis yield of CD34+ cells than G-CSF alone (OR, 5.33; 95%, 4.34-6.55). It was further discovered that G-CSF+plerixafor could mobilize more CD34+ cells into PB, which was beneficial for the next transplantation in both randomized controlled (MD, 18.30; 95%, 8.74-27.85) and single-arm (MD, 20.67; 95%, 14.34-27.00) trials. Furthermore, G-CSF+plerixafor did not cause more treatment emergent adverse events than G-CSF alone (OR, 1.25; 95%, 0.87-1.80). Conclusions: This study suggests that the combination of G-CSF and plerixafor, resulted in more patients with MM, NHL, and HL, achieving the predetermined apheresis yield of CD34+ cells, which is related to the more effective mobilization of CD34+ cells into PB. [ABSTRACT FROM AUTHOR]

PURPOSE: Fertility preservation was designed to help young patients overcome complications of cancer treatments, but its effectiveness is unknown. We sought to investigate how often patients with cancer are offered fertility preservation and if patients offered fertility preservation are more likely to have offspring. METHODS: We searched Embase (through 2022) and PubMed (through 2022). Our broad computerized search strategy was built upon using the keywords "chemotherapy," "radiation," and "fertility." The search took place on December 1, 2022. We included randomized and observational studies and excluded reviews and case reports/series. RESULTS: Eighty-five articles that answered at least one of the research questions were included. Studies assessing fertoprotective therapies often rely on surrogate markers for fertility. Multiple factors affect these markers of fertility. The median premature ovarian failure rate among the intervention group was 18% (IQR, 12%-20%), and among the control group, it was 25% (IQR, 19%-33%). Five of 11 studies reported a significant benefit from fertoprotective therapy. Pregnancies occurred in a median of 21% (IQR, 6%-52%) of patients in the intervention group and 11% (IQR, 7-44) of patients in the control group, with three of seven studies reporting a higher percentage of pregnancies among the intervention group. CONCLUSION: We reviewed the literature on several questions surrounding fertility preservation and found that there is limited and low-quality research on these therapies in cancer. Hence, there is a strong need for studies, especially randomized studies, that follow patients with cancer who undergo fertility preservation and assess outcomes in which patients are most interested. [ABSTRACT FROM AUTHOR]

Introduction: Amdizalisib (HMPL-689) is an ATP-competitive PI3Kδ inhibitor currently under investigation for treating Hodgkin's lymphoma. This study aimed to evaluate the metabolism, excretion, pharmacokinetics, and safety profile of amdizalisib in healthy human subjects to support its clinical application. Methods: This Phase I clinical trial included six healthy Chinese male volunteers who received a single oral dose of 30 mg/100 µCi [14C]amdizalisib suspension. Blood, urine, and fecal samples were collected to analyze pharmacokinetics, metabolic pathways, and excretion patterns. Results: Amdizalisib was rapidly absorbed, with a median Tmax of 2.5 h. The Cmax of 244 ± 48.9 ng/mL, and AUC0-t was 1870 ± 474 h ng/mL after a single oral dose. The blood-to-plasma total radioactivity ratio ranged from 0.561 to 0.645, indicating no significant affinity of [14C]amdizalisib and its metabolites to blood cells and the radioactive material is mainly distributed in plasma. Excretion was primarily via feces and urine, with 62.08% ± 3.00% and 37.15% ± 2.84% of the dose recovered, respectively, and over 94% of the drug excreted within 96 h. The parent drug was the main radioactive component in plasma (51.45% of total radioactivity). Additionally, 11 metabolites were identified, and the metabolic pathways include oxidation on the benzene or pyrimidine rings and conjugation with cysteine or glucuronic acid. The major metabolites in plasma were the di-oxidized and hydrogenated product (M424) and the mono-oxidized product (M406-2), accounting for 16.67% and 20.91%, respectively. Both of them are also the major radioactive components in urine and feces, among of which M424 accounted for 21.01% and 14.26%, M406-2 accounted for 8.08% and 11.30%, of the administered dose in urine and feces, respectively. In addition, the di-oxidized and methylated product (M436) was one of the major metabolites in feces accounting for 17.7% of the administered dose. Few of the parent drug was found in urine and feces, suggesting primary metabolized in the liver. No serious adverse events or drug-related deaths occured, with diarrhea as the most common adverse event. Discussion: These findings demonstrate that amdizalisib is rapidly absorbed, extensively metabolized, and primarily excreted via feces and urine, supporting its continued development as a potential therapeutic for Hodgkin's lymphoma. Systematic Review Registration: https://www.chinadrugtrials.org.cn/, identifier CTR20212448. [ABSTRACT FROM AUTHOR]

Background: Bleomycin is an oncolytic and antibiotic agent used to treat various human cancers because of its antitumor activity. Unfortunately, up to 46% of the patients treated with bleomycin develop drug-induced interstitial lung disease (DIILD) and potentially life-threatening interstitial pulmonary fibrosis. Tools and biomarkers for predicting and detecting DIILD are limited. Therefore, we aimed to evaluate the feasibility of 18F-FDG PET/CT, PET radiomics, and machine learning in distinguishing DIILD in an explorative pilot study. Methods: Eighteen Hodgkin's lymphoma (HL) patients, of whom 10 developed DIILD after treatment with bleomycin, were retrospectively included. Five diffuse large B-cell lymphoma (DLBCL) patients were included as a control group since they were not treated with bleomycin. All patients underwent 18F-FDG PET/CT scans before (baseline) and during treatment (interim). Structural changes were assessed by changes in Hounsfield Units (HUs). The 18F-FDG PET scans were used to assess metabolic changes by examining the feasibility of 504 radiomics features, including the mean activity of the lungs (SUVmean). A Random Forest (RF) classifier evaluated the identification and prediction of DIILD based on PET radiomics features. Results: HL patients who developed DIILD showed a significant increase in standard SUV metrics (SUVmean; p = 0.012, median increase 37.4%), and in some regional PET radiomics features (texture strength; p = 0.009, median increase 101.6% and zone distance entropy; p = 0.019, median increase 18.5%), while this was not found in HL patients who did not develop DIILD and DLBCL patients. The RF classifier correctly identified DIILD in 72.2% of the patients and predicted the development of DIILD correctly in 50% of the patients. There were no significant differences in HUs over time within all three patient groups. Conclusions: Our explorative longitudinal pilot study suggests that certain regional 18F-FDG PET radiomics features can effectively identify DIILD in HL patients treated with bleomycin, as significant longitudinal increases were observed in SUVmean, texture strength, and zone distance entropy after the development of DIILD. The metabolic activity of these features did not significantly increase over time in DLBCL patients and HL patients who did not develop DIILD. This indicates that 18F-FDG PET radiomics, with and without machine learning, might serve as potential biomarkers for detecting DIILD. [ABSTRACT FROM AUTHOR]

The letter to the editor discusses the importance of evidence-based follow-up strategies for patients with lymphoma in complete remission. It highlights the lack of high-quality studies supporting routine imaging and emphasizes the need for prospective trials to determine the effectiveness of such practices. The letter suggests that routine imaging may offer minimal to no benefit while contributing to unnecessary costs, anxiety, and medicalization. It calls for a rational approach to follow-up care and stresses the importance of providing patients with reliable information for well-informed decisions. [Extracted from the article]

Summary: Background: There are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma. Aims: The aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD. Methods: We searched Embase, PubMed and Scopus from inception to 30 April 2024 to identify population‐based cohort studies that evaluated the risk of lymphoma in patients with IBD in comparison with those without IBD. We carried out random‐effects meta‐analyses and estimated pooled relative risks (RRs) with 95% confidence intervals (CIs). Results: We identified 23 eligible studies reporting 2078 lymphoma events in 656,731 patients with IBD. Patients with IBD had 30% higher odds of lymphoma (RR = 1.30 [95% CI: 1.21–1.40]). The risk of developing both Hodgkin's lymphoma (nine studies, RR = 1.29 [95% CI: 1.06–1.53]) and non‐Hodgkin's lymphoma (16 studies, RR = 1.31 [95% CI: 1.20–1.42]) was increased in patients with IBD (p for interaction = 0.881). The increased risk of lymphoma was observed in both Crohn's disease (17 studies, RR = 1.54 [95% CI: 1.27–1.80]) and ulcerative colitis (20 studies, RR = 1.22 [95% CI: 1.09–1.35]) (p for interaction = 0.026). Meta‐regression demonstrated that mean age of patients, study year, mean study follow‐up duration, and percentages of immunomodulators and biologics use did not influence study outcome. Conclusions: The risk of lymphoma is only modestly increased in patients with IBD, with Crohn's disease having a slightly higher risk than ulcerative colitis. In IBD, there appears to be no difference between the risks of Hodgkin's and non‐Hodgkin's lymphoma. [ABSTRACT FROM AUTHOR]

Background: Karyomegalic interstitial nephritis (KIN) is a rare renal diagnosis associated with both genetic and medication etiologies. The primary gene associated with KIN is the FAN1 gene which encodes a protein responsible for DNA interstrand repair. Common medication triggers of KIN are chemotherapeutic agents, especially those which disrupt DNA structure such as carboplatin. Despite overlap between these mechanisms, it has not clearly been established if medication usage requires an underlying genetic predisposition for triggering KIN or if medications alone are sufficient. This ambiguous pathogenesis can make it difficult to appropriately assess risk of KIN development when starting patients on one of the known KIN-inducing therapies. Additionally, brentuximab vedotin, an antibody–drug conjugate directed against CD30, has not been previously implicated in KIN development. Case presentation. We present a 49-year-old woman previously diagnosed with metastatic Hodgkin's lymphoma who was treated with doxorubicin, bleomycin, vinblastine, and dacarbazine, then 3 cycles of ifosfamide, carboplatin, etoposide, all of which were discontinued due to side effects. Following an episode of acute kidney injury, the serum creatinine was 1.09 mg/dL. She then received 2 doses of brentuximab, the serum creatinine rose, and the drug was discontinued. Kidney biopsy done 2 months after brentuximab and 5 months following ifosfamide therapies showed karyomegalic interstitial nephritis. Genetic evaluation showed no FAN1 gene mutations. The patient was started on pembrolizumab; no steroids were given due to concerns about interference with lymphoma immunotherapy. She remains with stable disease and stable chronic kidney disease. Conclusions: This case presents a patient who developed KIN with a progressively rising serum creatinine after ifosfamide, carboplatin and brentuximab treatment. Although ifosfamide and carboplatin have known associations with the development of KIN, this case raises the possibility that brentuximab, which has a different mechanism of action, also may be associated with KIN. Additionally, the genetic findings demonstrate that drug-induced KIN can develop in the absence of FAN1 mutations, a finding not previously reported. [ABSTRACT FROM AUTHOR]

The article in the Blood Cancer Journal presents a simplified, two-factor clinical prognostic scoring system for patients with newly diagnosed Hodgkin Lymphoma. The study analyzed patient data to create a prognostic model based on age and albumin levels, resulting in a Simplified Prognostic Score (SPS) that categorizes patients into low, intermediate, and high-risk groups. The SPS showed higher concordance index compared to established prognostic models and offers a simple and globally applicable tool for predicting outcomes in patients with Hodgkin Lymphoma. The study acknowledges limitations and the need for further validation in diverse populations before implementing treatment strategies based on the SPS. [Extracted from the article]

Summary The outcome of 221 patients with bulky (≥10 cm) classic Hodgkin lymphoma (cHL) treated with doxorubicin, bleomycin, vinblastine, dacarbazine and consolidative radiotherapy (RT) only in those with a positive end‐of‐treatment (EOT) positron emission tomography (PET) scan was evaluated. With a median follow‐up of 9.6 years, 5‐ and 10‐year progression‐free survival (PFS) in EOT PET‐negative cases were 94.0% and 90.4%, respectively, and in PET‐positive cases, 5/10‐year PFS was 64.6% (p < 0.001), with 15% overall receiving RT. Five‐year PFS for Deauville (D) score DX/D1–3 was 93.6%, compared with D4 66.7% (p < 0.001) and D5 33.3% (p < 0.001). Omission of RT in EOT PET‐negative cases is associated with excellent long‐term outcomes in bulky cHL. [ABSTRACT FROM AUTHOR]

Summary This good practice paper (GPP) is intended to support clinicians in assessing patient fitness for bleomycin and in management of bleomycin pulmonary toxicity (BPT) where it occurs. Bleomycin, originally developed as an antibiotic in the 1960s, has been a cornerstone of therapy for classical Hodgkin lymphoma (CHL) since results of its use in combination with doxorubicin, vincristine and dacarbazine (ABVD) were first published by Bonadonna et al in 1975 1. The same author recognised high rates of respiratory morbidity in these patients 2, and bleomycin‐;related pulmonary toxicity (BPT) is now a well‐;recognised and feared complication with its use. ABVD and BEACOPP/ BEACOPDac (bleomycin, cyclophosphamide, etoposide, doxorubicin, vincristine and prednisolone, with procarbazine or dacarbazine) are standard first‐;line treatments in CHL patients, but considerable variation remains in assessing patient fitness for bleomycin both clinically and with respiratory investigations. A recent survey of British haematologists regularly using bleomycin revealed that 87.5% have no local protocols for assessing patients in an evidence‐;based fashion, with wide variations in practice captured in the same survey (personal data). A working group was established and a literature review undertaken with the goal of presenting practical recommendations for clinicians regarding bleomycin use based on available evidence and expert opinion. [ABSTRACT FROM AUTHOR]

ABSTRACT Risk of cardiovascular disease (CVD) in patients with classical Hodgkin lymphoma (cHL) undergoing contemporary treatment is unclear. cHL patients ≥ 18 years at diagnosis treated with doxorubicin‐containing chemotherapy between 2000 and 2022 were matched 1:5 with comparators on birth year, sex, and Charlson Comorbidity Index at time of matching (score of 0 or ≥ 1). Cause‐specific cumulative incidence of a composite of CVDs with corresponding 95% confidence intervals (CIs) were computed with death and lymphoma relapse as competing events (i.e., by censoring individuals at such occurrences) using the Aalen‐Johansen estimator. A total of 1905 patients and 9525 comparators with a median follow‐up of 10 years (interquartile range, [IQR]: 5.9–17.4). Median age was 39 years (IQR: 27–56), median cumulative doxorubicin dose was 250 mg/m2 (IQR: 200–300). The CVD cumulative incidences were 4.7% (95% CI: 3.6–5.7) for patients versus 2.6% (95% CI: 2.3–2.9) for comparators at 5 years, 8.9% (95% CI: 7.2–10.5) versus 5.5% (95% CI: 4.9–6.0) at 10 years, and 17.0% (95% CI: 14.1–19.9) versus 8.2% (95% CI: 7.4–9.0) at 15 years. CVD remains a substantial effect after contemporary treatment for cHL, suggesting that awareness of symptoms and a low threshold for referral to diagnostic examination are still important measures during survivorship. [ABSTRACT FROM AUTHOR]

Background: In children, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Given the lack of data on the best chemotherapy regimen, there is a knowledge gap in best management. Methods: This retrospective study included all pediatric patients with NLPHL diagnosed and treated at the Children's Cancer Hospital, Egypt (2007–2018). We analyzed the clinical characteristics, and treatment outcome according to disease stage (early and advanced), treatment strategy (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD] or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] and explored the prognostic factors for progression-free survival. Results: The median age at diagnosis was 12 years; 40 (68%) patients had early-stage disease, and 19 (32%) had advanced-stage disease. The median follow-up was 70 months; the 5-year EFS and OS were 75% and 97%, respectively. The 5-year EFS was 78% for early-stage disease and 60% for advanced-stage disease; the 5-year OS was 100% for early-stage disease and 88% for advanced-stage disease. The patients who underwent R-CHOP had a better 3-year EFS (100%) compared with those who underwent ABVD (65%) regimen (P = 0.01). Seventeen (25%) patients relapsed: 9/40 (22%) had early-stage disease, and 8/19 (42%) had advanced-stage disease. Splenic involvement, mediastinal disease, extranodal disease, and slow early response were independent predictors of relapse risk. Conclusion: Pediatric patients with early-stage NLPHL have an excellent prognosis, with a 5-year OS of 100%. However, those with advanced stages had a high relapse rate. R-CHOP was associated with a better response and relapse-free rate than ABVD. [ABSTRACT FROM AUTHOR]

Since their initial approval as single agent therapy for multiply relapsed/refractory Hodgkin lymphoma (HL), the PD-1 inhibitors nivolumab and pembrolizumab have been incorporated into second-line salvage regimens, and they are being investigated in upfront therapy of newly diagnosed patients. As second-line therapy in combination with brentuximab vedotin or multi-agent chemotherapy, nivolumab and pembrolizumab provide high complete remission rates and durable progression-free survival after consolidative autologous stem cell transplant. Incorporation of these agents into frontline chemotherapy regimens is feasible, and early results from a Phase III trial of nivolumab-AVD compare favorably with the existing standard for advanced stage HL, brentuximab vedotin plus AVD. As nivolumab and pembrolizumab move into earlier lines of HL therapy, open research questions include the efficacy of checkpoint inhibitor regimens in patients who relapse after frontline exposure to nivolumab or pembrolizumab; the selection of patients with relapsed HL who can achieve durable remissions without autologous stem cell transplant; and the efficacy of the PD-1 inhibitors in the frontline therapy of patients with early stage Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

Vincristine, a vinca alkaloid, is used in chemotherapy protocols for cancers such as acute leukemia, Hodgkin's disease, neuroblastoma, cervical carcinoma, lymphomas, breast cancer, and melanoma. Among the common adverse effects of vincristine is peripheral neuropathy, with most patients receiving a cumulative dose over 4 mg/m2 who develop varying degrees of sensory neuropathy. The onset of vincristine-induced peripheral neuropathy can greatly affect patients' quality of life, often requiring dose adjustments or the discontinuation of treatment. Moreover, managing vincristine-induced peripheral neuropathy is challenging, with few effective therapeutic strategies available. In the past decade, preclinical studies have explored diverse substances aimed at preventing or alleviating VIPN. Our review consolidates these findings, focusing on the analgesic efficacy and potential mechanisms of various agents, including pharmaceutical drugs, natural compounds, and antioxidants, that show promise in reducing neuropathic pain and protecting neural integrity in preclinical models. Key novel therapeutic options, such as metabolic agents (liraglutide), enzyme inhibitors (ulinastatin), antipsychotics (aripiprazole), interleukin-1 receptor antagonists (anakinra), hormones (oxytocin), and antioxidants (thioctic acid), are highlighted for their neuroprotective, anti-inflammatory, and antioxidant effects. Through this synthesis, we aim to enhance the current understanding of VIPN management by identifying pharmacological strategies that target critical molecular pathways, laying the groundwork for future clinical studies. By clarifying these novel pharmacological approaches and elucidating their mechanisms of action, this review provides a foundation for developing more effective VIPN treatment strategies to ultimately improve patient outcomes. [ABSTRACT FROM AUTHOR]

The article discusses a case of a young girl with a rare immune disorder called autoimmune lymphoproliferative syndrome (ALPS) due to a biallelic FASL gene mutation. The girl developed Hodgkin lymphoma and underwent a successful hematopoietic stem cell transplant as part of her treatment. The case highlights the challenges and successful management of ALPS-FASL and associated malignancies. The study emphasizes the importance of genetic analysis, regular monitoring, and appropriate treatment in such cases. [Extracted from the article]