Hodgkin's Disease Research Articles

Development of Bone Marrow Transplantation Strategies

The use of alternative stem cell sources, the growth of supportive healthcare facilities, and the expansion of indications for bone marrow transplantation (BMT) as well as partially matched donors from the same family are all continuing evolutionary trends as the use of BMT has been developed and expanded to include donors who are not related by blood but have Partial histocompatibility antigen compatibility. Although the outcomes of these transplants are not as good as those performed with first-degree siblings, patients with leukemia, aplastic anemia, and immunodeficiency disorders who cannot receive treatment otherwise they can receive it now. Patients suffering from diseases such as acute myeloid leukemia, acute lymphoblastic leukemia, and Hodgkin lymphoma also show success with autologous bone marrow transplants. Furthermore, bone marrow or blood stem cell support is used after intensive chemotherapy. Patients with stage II, III, and IV breast cancer can benefit from treatment with bone marrow cells found in peripheral blood. In this review, the most important developments in autologous and allogeneic bone marrow transplantation, the control of infectious diseases, and the use of gene therapy to alter genetic disorders that are transmitted from parents to their offspring through bone marrow or peripheral blood infusions are outlined.

The Impact of IgG Fc-Glycosylation on Disease Dynamics in Primary Sjögren's Disease- Insights from the Belgian Sjögren's Syndrome Transition Trial.

Glycans attached to the fragment crystallizable region (Fc) of IgG antibodies influence their pro- or anti-inflammatory effector function. We aimed to explore the interrelation between the Fc-glycosylation profile and disease transition, disease activity and outcome in patients with suspected and confirmed primary Sjögren's Disease (SjD). IgG Fc-sialylation and IgG Fc-galactosylation serum levels were determined in 300 patients from the Belgian Sjögren's Syndrome Transition Trial (BeSSTT). This cohort includes both suspected and confirmed SjD patients meeting the 2016 ACR/EULAR criteria. Salivary gland involvement was evaluated through ultrasonography (Hocevar score 0-48) and histopathology (focus score). The relative amount of sialylated and galactosylated IgG was determined by capillary electrophoresis after using the endoS endoglycosidase based assay. SjD patients exhibited significantly lower sialylation and galactosylation levels versus asymptomatic anti-SSA carriers and sicca patients. Lower sialylation and galactosylation levels were significantly associated with an increase in B-cell activation markers and distinct autoantibody profiles, particularly with multiple autoantibody reactivities. They were also linked to histopathological salivary gland alterations, higher Hocevar scores and importantly with risk factors for non Hodgkin lymphoma (NHL) development. In contrast, mono-anti-Ro60 positive and anti-SSA negative SjD patients had normal IgG Fc-glycosylation. This study points to a novel role of IgG Fc-glycosylation in SjD in predicting disease transition, monitoring disease activity, and risk stratification for NHL development.

Efficiency of PET-CT in Reducing the Usage of Radiotherapy in Childhood Hodgkin Lymphoma: A Single Center Experience

Efficiency of PET-CT in Reducing the Usage of Radiotherapy in Childhood Hodgkin Lymphoma: A Single Center Experience

Real-world treatment outcomes for Hodgkin lymphoma in South Africa: a prospective observational study

BackgroundProspective data from sub-Saharan Africa suggests that treatment outcomes for people living with HIV (PWH) with Hodgkin lymphoma (HL) are similar to those without HIV. However, real-world data from high-resource settings and retrospective studies from sub-Saharan Africa, suggest inferior outcomes. We set out to evaluate the real-world treatment outcomes for HL in South Africa to better understand the disparate outcomes.MethodsWe established a prospective, observational cohort of newly diagnosed, adult (≥ 18 years) HL cases recruited from Chris Hani Baragwanath Academic and Netcare Olivedale Hospitals in Johannesburg, South Africa between March 2021 and March 2023. Participants were followed for up to 18 months after enrollment with data censored on December 23rd, 2023. The primary endpoint was 1-year overall survival.ResultsWe enrolled 47 participants with HL including 31 PWH and 16 HIV-negative. Advanced stage disease and B symptoms were common at time of diagnosis irrespective of HIV status. Bone marrow biopsy, performed during the work-up and evaluation of cytopenias, provided the initial diagnosis of HL in 16/31 (52%) PWH. HIV status and bone marrow involvement were associated with early mortality (within 3 months of diagnosis) and a poorer 1-year overall survival from diagnosis (HIV: 55% vs. 88%; p = 0.03; bone marrow involvement: 50% vs. 80%; p = 0.02). Among evaluable participants, those that received at least 6 cycles of chemotherapy and underwent response assessment, there was no difference between those with and without HIV.ConclusionTraditional laboratory markers of poor prognosis including anemia, lymphopenia and hypoalbuminemia were more common among PWH and those with bone marrow involvement and suggest high risk disease. A better understanding of the drivers of these aggressive presentations is warranted to ensure more PWH are able to tolerate chemotherapy.

Visceral Leishmaniasis Following A+AVD Treatment in a Patient with Classical Hodgkin's Lymphoma: A Case Report and Review of the Literature.

We present the case of a 43-year-old Caucasian man who developed visceral leishmaniasis (VL) following treatment with a combination of brentuximab vedotin and doxorubicin, vinblastine, and dacarbazine (A+AVD) for advanced-stage classical Hodgkin's lymphoma (cHL). The patient initially showed a favorable response to the treatment, but shortly after completing six cycles, he experienced recurrent fever, splenomegaly, and severe anemia. Extensive infectious disease evaluations led to a diagnosis of VL, confirmed by PCR testing. The patient was treated with amphotericin B, resulting in full clinical recovery. In addition to presenting this rare case, we conducted a full review of the literature on VL in the context of hematological disorders, including non-Hodgkin's lymphoma, splenic marginal zone lymphoma, and other lymphoproliferative diseases. This review highlights the increasing prevalence of VL in immunocompromised individuals, particularly those undergoing treatments like chemotherapy or immunotherapy, and underscores the importance of considering VL in differential diagnoses when such patients present with persistent fever and splenomegaly.

Antibody–drug conjugates and immune checkpoint inhibitors in cancer treatment: a systematic review and meta-analysis

Although antibody–drug conjugate (ADC) or immune checkpoint inhibitors (ICIs) alone fosters hope for the treatment of cancer, the effect of single drug treatment is limited and the safety profile of ADC and ICI therapy remains unclear. This meta-analysis aimed to examine the efficacy and safety of the combination of ADC and ICI therapy. This study type is a systematic review and meta-analysis. Literature retrieval was carried out through PubMed, Embase, Cochrane from inception to Jun. 5, 2024. Then, after data extraction, overall response rate (ORR) and adverse effects (AEs) were used to study its efficiency and safety. Publication bias was also calculated through Funnel plot, Begg's Test and Egger's test. Heterogeneity was investigated through subgroup and sensitivity analysis. The research protocol was registered with the PROSPERO (CRD42023375601). A total of 12 eligible clinical studies with 584 patients were included. The pooled ORR was 58% (95%CI 46%, 70%). Subgroup analysis showed an ORR of 77% (95%CI 63%, 91%) in classical Hodgkin lymphoma (cHL) and an ORR of 73% (95%CI 56%, 90%) in non-Hodgkin lymphoma (NHL). The most common AEs was peripheral neuropathy (38.0%). Meanwhile, AEs on skin (13.1–20.0%) and digestive system (9.0–36.0%) was hard be overlooked. ADC + ICI therapy may be recommended in cancer treatment, especially in cHL and NHL. However, strategies to manage toxicities warranted further exploration.

Vinblastine-Induced Posterior Reversible Encephalopathy Syndrome in Pediatric Hodgkin Lymphoma

AbstractPosterior reversible encephalopathy syndrome (PRES) is a critical care scenario seen with several etiologies. We report a pediatric case of Hodgkin lymphoma presenting with paraneoplastic features of nephrotic syndrome (NS). Diagnosis was confirmed with positron emission tomography-computed tomography scan and immunohistochemistry of the tissue biopsy. Remission for NS was achieved within a week of starting chemotherapy (ABVD–adriamycin, bleomycin, vinblastine, and dacarbazine). After the second cycle, he developed headache, seizures, and hypertension, requiring intensive care management. Magnetic resonance imaging brain was suggestive of PRES. The condition was managed with antihypertensives, antiepileptics, and supportive care. Considering all the risk factors for PRES including the drug, vinblastine, further chemotherapy was administered with only ABD regimen. The child attained complete remission after six cycles of chemotherapy and did not have any further episodes of hypertension or seizures. This case highlights the rare complication of vinblastine in a complicated lymphoid malignancy.

Ubiquitin-Mediated Effects on Oncogenesis during EBV and KSHV Infection.

The Herpesviridae include the Epstein-Barr Virus (EBV) and the Kaposi Sarcoma-associated Herpesvirus (KSHV), both of which are oncogenic gamma-herpesviruses. These viruses manipulate host cellular mechanisms, including through ubiquitin-mediated pathways, to promote viral replication and oncogenesis. Ubiquitin, a regulatory protein which tags substrates for degradation or alters their function, is manipulated by both EBV and KSHV to facilitate viral persistence and cancer development. EBV infects approximately 90% of the global population and is implicated in malignancies including Burkitt lymphoma (BL), Hodgkin lymphoma (HL), post-transplant lymphoproliferative disorder (PTLD), and nasopharyngeal carcinoma. EBV latency proteins, notably LMP1 and EBNA3C, use ubiquitin-mediated mechanisms to inhibit apoptosis, promote cell proliferation, and interfere with DNA repair, contributing to tumorigenesis. EBV's lytic proteins, including BZLF1 and BPLF1, further disrupt cellular processes to favor oncogenesis. Similarly, KSHV, a causative agent of Kaposi's Sarcoma and lymphoproliferative disorders, has a latency-associated nuclear antigen (LANA) and other latency proteins that manipulate ubiquitin pathways to degrade tumor suppressors, stabilize oncogenic proteins, and evade immune responses. KSHV's lytic cycle proteins, such as RTA and Orf64, also use ubiquitin-mediated strategies to impair immune functions and promote oncogenesis. This review explores the ubiquitin-mediated interactions of EBV and KSHV proteins, elucidating their roles in viral oncogenesis. Understanding these mechanisms offers insights into the similarities between the viruses, as well as provoking thought about potential therapeutic targets for herpesvirus-associated cancers.

EXPRESSION OF VITAMIN D3 RECEPTOR IN TUMOR TISSUE AND RELATIONSHIP BETWEEN CLINICAL FEATURES, PROGNOSTIC INDICATORS AND EXPRESSION OF VITAMIN D3 RECEPTOR IN HODGKIN LYMPHOMA

<p><strong>Background and objectives:</strong> In our study, we aimed to investigate the expression of vitamin D receptor and the relationship between clinical features, prognostic indicators, and expression of vitamin D receptor in Hodgkin lymphoma. <strong>Materials and Methods:</strong> Pathology records and medical files of patients with Hodgkin lymphoma were evaluated. Forty-two tissue samples were analyzed retrospectively. Vitamin D receptor staining was performed with immunohistochemistry. The patients were divided into low, medium, and intense staining subgroups. The demographic data, clinical and biochemical values of patients were reviewed retrospectively, and the relationship between clinical features, prognostic indicators, and vitamin D receptor expressions were examined. <strong>Results:</strong> VDR staining was positive in Reed-Sternberg cells of all Hodgkin lymphoma patients. The cases were divided into three groups according to VDR staining intensity as low, medium and intense staining and compared with known clinical prognostic parameters. Only the presence of symptom B was statistically significantly different. Gender, bone marrow involvement, extralymphatic involvement, mediastinal mass, bulky mass, mean leukocyte count, and treatment response were associated with vitamin D receptor staining intensity, but they were statistically insignificant. <strong>Conclusion: </strong>Our study is the second study showing VDR in tumor Hodgkin lymphoma tumor tissues and is meant to be the first to evaluate its association with clinical and biochemical prognostic laboratory tests. Vitamin D receptor staining in all Hodgkin lymphoma patients led to the conclusion that VDR can be used in the histopathological differential diagnosis of HL. More studies are needed to assess and demonstrate the relationship between prognostic and diagnostic indicators and vitamin D receptor intensity of immunohistochemically detected VDR in tumor tissues of Hodgkin lymphoma. Also, further studies with serum vitamin D levels and other histologic subtypes can provide more reliable results.</p><p> </p><p><strong> Article visualizations:</strong></p><p><img src="/-counters-/soc/0715/a.php" alt="Hit counter" /></p>

Decreased PU.1 expression in mature B cells induces lymphomagenesis.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, accounting for 30% of non-Hodgkin lymphomas. Although comprehensive analysis of genetic abnormalities has led to the classification of lymphomas, the exact mechanism of lymphomagenesis remains elusive. The Ets family transcription factor, PU.1, encoded by Spi1, is essential for the development of myeloid and lymphoid cells. Our previous research illustrated the tumor suppressor function of PU.1 in classical Hodgkin lymphoma and myeloma cells. In the current study, we found that patients with DLBCL exhibited notably reduced PU.1 expression in their lymphoma cells, particularly in the non-germinal center B-cell-like (GCB) subtype. This observation suggests that downregulation of PU.1 may be implicated in DLBCL tumor growth. To further assess PU.1's role in mature B cells invivo, we generated conditional Spi1 knockout mice using Cγ1-Cre mice. Remarkably, 13 of the 23 knockout mice (56%) showed splenomegaly, lymphadenopathy, or masses, with some having histologically confirmed B-cell lymphomas. In contrast, no wild-type mice developed B-cell lymphoma. In addition, RNA-seq analysis of lymphoma cells from Cγ1-Cre Spi1F/F mice showed high frequency of each monoclonal CDR3 sequence, indicating that these lymphoma cells were monoclonal tumor cells. When these B lymphoma cells were transplanted into immunodeficient recipient mice, all mice died within 3 weeks. Lentiviral-transduced Spi1 rescued 60% of the recipient mice, suggesting that PU.1 has a tumor suppressor function invivo. Collectively, PU.1 is a tumor suppressor in mature B cells, and decreased PU.1 results in mature B-cell lymphoma development.

Fifteen-Year Experience of a Single Institution: Outcomes for Early-Stage Hodgkins Lymphoma Comparing Chemotherapy Alone Versus Combined Modality Therapy

Doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy is the current standard treatment for early-stage Hodgkins lymphoma (HL). The use of consolidative radiation therapy (RT) in addition to chemotherapy may lead to better survival rates but is controversial because of concerns about long-term toxicity. The aim of this study is to compare outcomes of patients receiving ABVD chemotherapy alone (CTX alone) versus ABVD with consolidative RT (CMT). A single-institution, retrospective review of patients with HL diagnosed from 2000 to 2014 was conducted. Patients were identified from the National Cancer Database. Inclusion criteria included patients aged ≥18 years, with stage I or II HL, who received ABVD with a complete response with/without CMT. Consolidative RT must have been started within 90 days of completing chemotherapy. Institutional review board approval was obtained. Follow-up details and treatment responses were collected from medical record reviews. Standard statistical analysis and Kaplan-Meier curves were used to estimate relapse-free survival (RFS). One hundred and 8 patients with early-stage HL were identified. The median age at diagnosis was 31 years (range, 19-72). Most patients were female (63%) and Caucasian (65%). stage II HL was present in 89%of patients, 89% had an Eastern Cooperative Oncology Group score of 0 or 1, 35% had B symptoms, and 9% had extranodal involvement. A total of 52.8% received CMT (n = 57) and 47.2% received CTX alone (n = 51). The CMT group had fewer cycles of chemotherapy compared to the CTX-alone group (mean cycles, 5.2 vs 5.7, P = 0.045). Twenty-four relapse events occurred in the CTX-alone group, while no relapse events occurred in the CMT group. RFS at 10 years was significantly improved in the CMT group (100%) compared to CTX alone (47.4%, P < .0001; HR = .03, P < .001). ABVD with consolidative RT was associated with improved RFS. Further studies of toxicity comparisons, advanced stages, and nonfavorable HL are warranted.

The Vitamin C Level in Cases with Hematological Malignancies

Background: Oxidative stress plays a significant role in the pathogenesis of hematological malignan-cies. Vitamin C, known for its antioxidant properties, has garnered attention in this context. There-fore, we investigated vitamin C levels in patients with hematological malignancies and evaluated the relationship between vitamin C levels and response to treatment. Materials and Methods: Our study examined 150 cases of hematological malignancies and 30 he-althy cases. The vitamin C levels of patients with hematological malignancies were compared with those of the healthy group. Results: Vitamin C levels in cases of acute myeloblastic leukemia (n=30) (p&amp;lt;0.001), acute lympho-blastic leukemia (n=30) (p&amp;lt;0.001), Hodgkin lymphoma (n=30) (p&amp;lt;0.001), diffuse large B-cell lympho-ma (n=30) (p&amp;lt;0.001), and multiple myeloma (n=30) (p&amp;lt;0.001) were significantly lower compared to healthy individuals. There was a significant relationship between vitamin C levels and the response to treatment in cases with acute myeloblastic leukemia, acute lymphoblastic leukemia, Hodgkin lymphoma, diffuse large B-cell lymphoma, and multiple myeloma (p=0.020, p=0.020, p=0.040, p&amp;lt;0.001, p&amp;lt;0.001, respectively). In Hodgkin and non-Hodgkin lymphoma cases, a negative correla-tion was found between vitamin C levels and LDH and beta-2 microglobulin levels (p=0.001; p=0.008; p=0.017; p=0.019, respectively). Conclusions: Our study underscores the lower levels of vitamin C in patients with hematological malignancies compared to healthy individuals. Furthermore, the findings suggest that vitamin C levels could serve as a potential biomarker for predicting the response to treatment in these cases.

A novel germline Pregnane X Receptor (PXR) variant predisposing to Hodgkin lymphoma in two siblings

Hodgkin's lymphoma (HL) is the most common cancer in adolescents and young adults. A family history of HL increases the risk of developing HL in other family members. Identification of genetic predisposition variants in HL is important for understanding disease aetiology, prognosis, and response to treatment. Aberrant activation of the NF-κB pathway is a hallmark feature of HL, contributing to the survival and proliferation of the malignant cells' characteristic of HL.The family with multiple consanguineous marriages with siblings of diagnosed HL was examined by whole-exome sequencing. We found a germline homozygous variation in the PXR ligand binding domain (NM_003889.3:c.811G>A, p.(Asp271Asn)), which was classified as pathogenic by prediction tools and segregated in HL cases. Increased PXR expression was found in homozygous variant carriers compared to heterozygous carriers by quantitative real time PCR (qRT-PCR) and immunofluorescence staining of patients' formalin-fixed paraffin-embedded tissues showed upregulation of PXR, particularly in Hodgkin Reed/Sternberg (HRS) cells.Patients with homozygous PXR variant showed significantly high expression compared to PXR wild-type HL, heterozygous and controls (p = 0.0001, p = 0.0004 and p = 0.0001, respectively). PXR homozygous HRS cells had significantly higher PXR expression compared to PXR wild-type HRS cells (p < 0.0001, 3.27-fold change). Albeit PXR's prominent expression in cytoplasm of HRS cells, homozygous PXR HRS cells showed increased PXR expression in nucleus (p < 0.001).PXR is a member of the nuclear receptor superfamily and previous studies have demonstrated a pleiotropic effect of PXR on malignant transformation. Expression analysis showed that cell proliferation, apoptosis and inflammation related genes were deregulated, in homozygous PXR HL cases. This study provided clinical evidence to previously reported Sxr−/− mice model that develop multifocal lymphomas, had an aberrantly increased NF-κB expression and consistent inflammation. Further functional studies are needed to elucidate the exact mechanisms of action of PXR in HL pathogenesis.

Meta-analysis: Risk of lymphoma in patients with inflammatory bowel disease in population-based cohort studies.

There are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma. The aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD. 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). 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. 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.

Effect of consolidation radiation therapy on treatment outcomes of early-stage favorable Hodgkin lymphoma

Background. Early (stage I–II) classical Hodgkin lymphoma is a highly treatable malignant neoplasm. For many years, the standard treatment of early Hodgkin lymphoma has been combination therapy: polychemotherapy with subsequent consolidating radiation therapy. Aim. To retrospectively evaluate the results of treatment of stage I–II classical Hodgkin lymphoma in a favorable prognosis group using monotherapy and combination therapy (chemotherapy followed by consolidating radiotherapy). Materials and methods. The study included 58 patients aged 19–81 years (median age 36 years) diagnosed with stage I–II classical Hodgkin lymphoma with favorable prognosis; 23 (39.7 %) patients were men, 35 (60.3 %) were women. Depending on the treatment received, the patients were divided into two groups: 40 (69 %) patients received ABVD polychemotherapy, and 18 (31 %) patients received polychemotherapy followed by consolidating radiation therapy to the initial lesion zones with standard fractionation regimen (total dose 30 Gy). The Kaplan–Mayer method was used to evaluate overall, progression-free, recurrence-free, and event-free survival. Odds ratios and their 95 % confidence intervals were also calculated. The statistical significance of differences in survival was assessed using the log-rank test. The level of statistical significance was 0.05. Statistical data processing was carried out using the IBM SPSS Statistics 27 software and Microsoft Excel. Results. According to the results of our study, while in the total patient group a clear numerical advantage in survival (overall, progression-free, relapse-free and event-free survival) was observed in the combination therapy group compared to chemotherapy group (5.5, 13.2, 9.2 and 23.9 %, respectively), no preferred tactics were identified in the total patient group. However, considering a subgroup of patients with mediastinum involved in the tumor process, a statistically significant advantage of combined treatment over single-mode chemotherapy was determined for 2-year event-free survival (92.9 ± 6.9 % vs. 62.5 ± 9.9 %, respectively, p = 0.046). The risk of an adverse event is reduced by &gt;80 % (odds ratio 0.197; 95 % confidence interval 0.036–0.977) when using consolidating radiation therapy after chemotherapy.

Interpreting the Function of the IL-23/IL-17 Axis through Bioinformatics.

Bioinformatic analysis is a valuable tool that allows us to collect, archive, analyze, and disseminate biological data for further interpretation. Analysis of the IL-23/IL-17A axis and its receptors will provide us with essential information about their functions, interactions, and relationships with various diseases. This review aims to identify the central genes co-expressed in the IL-23/IL-17A axis and their receptors and to understand their ontology and modifying factors. We used several databases, including COXPRESdb to obtain the co-expressed genes, ShinyGO and ToppGene platforms to explore gene functional enrichment, and the NetworkAnalyst 3.0 platform for gene expression profiling. We found that genes encoding IL-23/IL-17A axis proteins and their receptors mainly respond to microbial components, participate in the inflammatory response, and are primarily associated with inflammatory and autoimmune diseases. In addition, we observed an association of the IL-23/IL-17 axis with Behcet's disease, Graft-versus-host disease, and Hodgkin's disease, although there is no direct evidence of their interaction. The IL-23/IL-17A axis is associated with several inflammatory and autoimmune pathologies. Therefore, we suggest further research to confirm its role in these pathologies and, if possible, use it as a therapeutic target.

Abstract C072: Evaluating the use of vincristine as a substitute for vinblastine in Hodgkin lymphoma treatment

Abstract Introduction: Classical Hodgkin lymphoma (HL) is a type of cancer originating from B lymphocytes, characterized by a high annual incidence globally. While the ABVD regimen (Adriamycin, Bleomycin, Vinblastine, and Dacarbazine) is the standard treatment, this study explores substituting Vinblastine with Vincristine (ABOD regimen) to potentially enhance efficacy and treatment outcomes. Purpose: The primary aim was to evaluate the efficacy of the ABOD regimen compared to the ABVD regimen in treating classical Hodgkin lymphoma. The study also aimed to identify factors influencing treatment response, relapse risk, and the indication for alternative treatments such as escalation therapy, salvage therapy, immunotherapy, and transplantation. Method: This retrospective study reviewed 83 patients diagnosed with classical HL and treated at the Military Cancer Center in Jordan from January 1, 2017, to February 1, 2023. Data on demographics, disease characteristics, treatment regimens, and outcomes were collected and analyzed using logistic regression and Chi-square tests to evaluate associations between variables and treatment outcomes. Results: The study included 83 patients, with a mean age of 35.67 years, and a predominance of females (60.24%). The most common subtype was nodular sclerosis (84.34%), with stage 4 disease being the most prevalent (45.12%). Treatment response after the second cycle of ABOD was significantly better in older patients. There was no significant association between bulky disease and treatment response or relapse risk. Younger patients required dose escalation more frequently, suggesting the ABOD regimen might be more suitable for older patients. Gender, histological subtype, and disease stage were not significantly associated with treatment response or relapse risk. Conclusion: The ABOD regimen, using vincristine instead of vinblastine, presents a viable alternative to the ABVD regimen for classical Hodgkin lymphoma treatment, particularly benefiting older patients due to favorable response rates and manageable toxicity. The findings highlight the need for further research to optimize treatment strategies for different patient subgroups and confirm the benefits of the ABOD regimen. Citation Format: Zaid Sarhan, Mousa Atmeh, Mohammad Al-Saudi, Abed AlFattah AlNsour, Osama Alghafri, Dia’a AlDin Sarhan, Raneem Al-Dalaeen. Evaluating the use of vincristine as a substitute for vinblastine in Hodgkin lymphoma treatment [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C072.

Protocol-Stipulated Dose Modification to Manage Chemotherapy-Induced Peripheral Neuropathy in Children, Adolescents, and Young Adults With High-Risk Hodgkin Lymphoma.

Brentuximab vedotin (BV) incorporation into frontline chemotherapy regimens improved outcomes for classic Hodgkin lymphoma (cHL). The shared mechanism of action of BV and vinca alkaloids as microtubulin inhibitors increased the potential risk of chemotherapy-induced peripheral neuropathy (CIPN). Rates of CIPN and use of protocol-stipulated dose modifications of a microtubulin inhibitor were examined on the Children's Oncology Group AHOD1331 study, which compared BV, doxorubicin, vincristine (VCR), etoposide, prednisone, cyclophosphamide (BV-AVE-PC; BV arm) with bleomycin containing doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC; standard arm) in patients with high-risk cHL ages 2-21 years. AHOD1331 required clinician grading and reporting of ≥grade 2 CIPN. Protocol-stipulated dose modifications of VCR preceded modification of BV for ≥grade 2 CIPN in the BV arm, but only required modification of VCR for ≥grade 3 in the standard arm. Outcomes included CIPN rates, dose modification of microtubulin inhibitors by study arm, clinical factors associated with dose modifications, and event-free survival (EFS) by the presence of dose modification. Among the 582 patients who began protocol therapy, 112 developed ≥grade 2 CIPN. Cumulative incidence of CIPN did not differ by study arm (19.2 v 19.8%, P = .91). CIPN dose modifications occurred more frequently in the BV arm (9.5% v 2.8%, P = .001); however, most patients with CIPN on the BV arm received full-dose BV. EFS did not differ by the presence of dose modifications after accounting for study arm, age, sex, and stage, although older age was significantly associated with the risk of VCR dose modifications for CIPN. A staged dose modification plan for vinca alkaloids and BV as administered in AHOD1331 minimized the effect of incorporating a second microtubulin inhibitor on CIPN without compromising treatment efficacy in the BV arm.

The effect of plerixafor on autologous stem cell mobilization, cell viability, and apheresis challenges

Abstract Objective The aim of this study was to determine the efficacy of plerixafor for hematopoietic stem cell (HSC) mobilization prior to autologous stem cell transplantation (aSCT) for patients with multiple myeloma (MM) and various lymphomas, using an oncologist-guided HSC collection goal and markers of cell viability. Methods A retrospective chart review of all aSCT patients at Yale New Haven Hospital between 2017 and 2021 who met diagnostic criteria for MM, non-Hodgkin, or Hodgkin lymphoma (n = 382) was undertaken. Logistic regression evaluated plerixafor’s effect on meeting the individual’s HSC goal. The use of t-tests determined plerixafor’s relationship to HSC yield and analysis of variance testing assessed its effect on cell viability. Results Mobilization with granulocyte colony–stimulating factor (G-CSF) and plerixafor (odds ratio [OR] = 0.08; P &amp;lt; .05) relative to G-CSF alone was negatively associated with meeting the individual’s HSC goal. Diffuse large B-cell lymphoma in patients mobilized with plerixafor yielded fewer HSCs than those without plerixafor (t = –2.78; P = .03). Mobilization regimen (P = .13) had no association with HSC viability. Mobilization failure with plerixafor was rare but occurred in patients with multiple risk factors, including exposure to several rounds of HSC-affecting chemotherapy. Conclusion Plerixafor is effective across multiple diagnoses using an oncologist-driven HSC collection endpoint. Its association with mobilization failure is likely attributable to its use in patients predicted to be poor mobilizers.

The causal effect of telomere length on the risk of malignant lymphoma: A Mendelian randomization study.

Telomere length (TL) has been implicated in the risk assessment of numerous cancers in observational studies. Nevertheless, the relationship between TL and malignant lymphoma remains unclear, displaying inconsistent patterns across different studies. A summary dataset for genome-wide association study of TL and malignant lymphoma was acquired from the OpenGWAS website. An extensive 2-sample Mendelian randomization (MR) analysis was performed, encompassing various methodologies such as MR-Egger, weighted median, weighted mode, simple mode, and the primary method of inverse-variance weighting (IVW). Sensitivity evaluations were performed using the Cochran Q test, MR-Egger regression, and leave-one-out analysis. The main method IVW revealed that TL substantially increased the risk of Hodgkin lymphoma (HL; odds ratio [OR] = 2.135; 95% confidence interval [CI] = 1.181-3.859; P = .012). Both the IVW and weighted median methods indicated statistical associations between genetically predicted TL and other types of non-HL (OR = 1.671, 95% CI = 1.009-2.768, P = .045; OR = 2.310, 95% CI = 1.033-5.169, P = .042). However, there was no association between TL and diffuse large B-cell lymphoma, follicular lymphoma, or mature T/natural Killer-cell lymphoma, and sensitivity analysis revealed no heterogeneity or horizontal pleiotropy, indicating that the causal effect was robust. Our study shows that TL plays different roles in different types of lymphomas. A longer TL significantly increases the risk of HL and other types of non-HL.