Treatment Strategies For Hodgkin Lymphoma Research Articles

HL-091 Role of Interim PET-CT Scan on Long Term Follow Up of Patients With Hodgkin Lymphoma: A Single-Center Study in a Developing Country

The Hodgkin lymphoma (HL) showed a good prognosis in Erbil city. However, a number of deaths were reported. The monitoring and treatment strategies for HL had improved in the last decade. To evaluate the prognostic value of interim PET/CT scan in HL patients and predict the survival outcome in addition to its effect on progression-free survival of HL patients. A retrospective cross-sectional study was conducted in Nanakali hospital in Erbil city in the Kurdistan region of Iraq through reviewing data of patients with Hodgkin lymphoma from the 1st of January, 2014 to the 31st of December, 2019 on a sample of seventy-five Hodgkin lymphoma patients. The diagnosis of Hodgkin lymphoma by a physician was done in regard to lymph biopsy by World Health Organization criteria. The PET/CT scan was done after two treatment cycles. PET/CT of HL patients was done in a private center in Erbil city (Media Diagnostic Center). The mean overall survival duration of HL patients was 5.39 years with an overall survival rate of 92% and the mean progression-free survival duration of HL patients was 5.04 years with a progression-free survival rate of 76%. The mean overall survival of HL patients with positive interim PET/CT was (4 years and a rate of 75%) which was lower than the mean overall survival of HL patients with negative interim PET/CT (7.2 years and a rate of 95.2%), with a significant difference (p<0.001). The interim PET/CT scan is useful in the prognosis of patients with Hodgkin lymphoma and in predicting overall survival and mortality.

Immunodeficiency-associated Hodgkin lymphoma

Introduction Hodgkin lymphoma (HL) can occur in different host conditions, i.e. in the general population and immunocompromised individuals, either during HIV infection or solid organ/hematopoietic transplantation and immunosuppressive drug treatment. Areas covered Areas covered include multidimensional characteristics of tumor cells and cellular composition of tumor microenvironment of HL. Current conventional treatments and new treatment strategies for HL in immunosuppressed patients, especially in persons living with HIV (PLWH), are also discussed. PubMed and MEDLINE were used for database searches to identify articles published from 1989 to 2020. Only articles or abstracts in English were considered for this Review Expert opinion In 2012, the International Agency for Research on Cancer -IARC- has considered the epidemiological and biological scientific evidence sufficient to establish that HIV induced immune deficiency is a cause of HL. Moreover, the risk of HL is substantially increased in people with iatrogenically acquired immune depression following organ transplantation. For people with post-transplant HL or for those with HIV/AIDS-associated HL, standard treatments mirror those in the general population. In the last decade, the combination of cART with anti neoplastic treatments, alongside with current anti-rejection therapies, has increased long-term survival of people with HL and acquired immune deficiencies. High dose chemotherapy and autologous stem cell transplantation have been favourably proven as salvage therapy in PLWH with relapsed and refractory HL. Immune checkpoint inhibitors emerged as an area of clinical investigation for relapsed and refractory HL in the general population. Pembrolizumab, an anti-programmed cell death protein 1 (PD-1) drug, resulted safe in PLWH indicating that PD-1 ligand assessment should be advisable in HIV-associated HL. In post-transplant-associated HL management is challenging because it must balance disease eradication with graft rejection, increased immunosuppression and life-threatening infections.

Updates in Treatment Strategies for Hodgkin Lymphoma.

Several options are available for frontline treatment of advanced-stage Hodgkin lymphoma (HL) and treatment of relapsed HL, each with inherent advantages and disadvantages. Clinicians must balance risk with benefit for the individual patient. At the NCCN 2019 Annual Congress: Hematologic Malignancies, Dr. Ranjana H. Advani summarized the current frontline treatment options for advanced-stage HL and outlined novel and emerging agents that may be incorporated as therapy options for relapsed disease.

Humanized anti-CD123 antibody facilitates NK cell antibody-dependent cell-mediated cytotoxicity (ADCC) of Hodgkin lymphoma targets via ARF6/PLD-1

CD123 (IL-3Rα) is frequently expressed by malignant Hodgkin lymphoma (HL) cells. Naked monoclonal antibodies (mAb) against HL lack clinical benefit, partially due to absence of natural killer (NK) cells in the tumor microenvironment. Here we show that the combination of a fully humanized anti-CD123 mAb (CSL362) and high-affinity Fcγ-receptor NK-92 cells (haNK) effectively target and kill HL cells in vitro. First, we confirmed high expression of CD123 in 2 of the 3 HL cell lines (KM-H2 and L-428), and its absence in NK cells. Cytotoxicity of haNK cells against CD123-positive HL cells was significantly higher in the presence of CSL362. This was also shown with IL-15-activated primary NK cells, although haNK cells showed a 10.87-fold lower estimated half-maximal stimulatory effective concentration (EC50). CSL362 facilitated a significant increase in the expression of CD107a, intracellular IFN-γ and TNF-α and enhanced expression of c-JUN, PLD-1, and ARF6 by NK cells. Inhibition of the ARF6–PLD-1 axis (NAV2729), but not of the MAPK pathway (U0126), completely abrogated CSL362-facilitated antibody-dependent cell-mediated cytotoxicity (ADCC) in haNK and activated primary NK cells. Our results support CD123 as an immunotherapeutic target for HL and the combination of NK cells and CSL362 as a treatment strategy for HL.

Successful treatment of primary bone marrow Hodgkin lymphoma with brentuximab vedotin: a case report and review of the literature

BackgroundHodgkin lymphoma usually presents with sequential enlargement of peripheral lymph nodes, and bone marrow invasion rarely occurs (approximately 3–5%). However, several cases have been reported as “primary” bone marrow Hodgkin lymphoma, especially among patients with human immunodeficiency virus and the elderly. This type of Hodgkin lymphoma is characterized by no peripheral lymphadenopathies and has been reported to have poorer prognosis.Case presentationA 38-year-old Japanese man was admitted to our hospital because of fever of unknown origin and pancytopenia without lymphadenopathies. Bone marrow examination revealed Hodgkin cells mimicking abnormal cells. These were positive for CD30, EBER-1, CD15, PAX-5, and Bob-1 and negative for Oct-2, CD3, CD20, surface immunoglobulin, CD56. On the basis of systemic evaluation and bone marrow examination, he was diagnosed with primary bone marrow Hodgkin lymphoma. We initiated therapy with DeVIC (dexamethasone, etoposide, ifosfamide, and carboplatin) therapy, but remission was not achieved. Then, the patient was treated with brentuximab vedotin combined with systemic chemotherapy (Adriamycin, vinblastine and dacarbazine), which was effective.ConclusionsThere is no established treatment strategy for Hodgkin lymphoma, and therapeutic outcomes using ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine)-like or CHOP (cyclophosphamide, Adriamycin, vincristine, and prednisone)-like regimens are reportedly poor. Only a few patients have been reported to achieve long-term remission. Through this case report, we suggest an alternative therapeutic option for primary bone marrow Hodgkin lymphoma.

Treatment strategy for patients with Hodgkin lymphoma.

Although Hodgkin lymphoma is a disease with a low incidence rate, there is a significant social resources perspective associated with this disease to ensure that adolescents and young adults are adequately treated and receive social reintegration. Consequently, Hodgkin lymphoma is considered an important disease in the field of oncology. Combined modality therapy, which combines chemotherapy and radiotherapy, has resulted in cure rates of more than 80% in patients with early stages of this disease, although long-term sequelae remain a problem. Response-adapted therapy using FDG-PET is being studied as a treatment strategy in an attempt to attenuate treatment to reduce toxicity in interim-PET negative cases and to enhance therapeutic intensity for interim-PET positive cases. In addition, brentuximab vedotin, which targets CD30 and anti-PD-1 antibodies, which represent immune checkpoint inhibitors, is effective even when treatment resistance develops after autologous transplantation. Both high cure rates and toxicity control are essential targets for treatment modalities of Hodgkin lymphoma. Long-term follow-up of secondary malignancy and heart and lung failure should be incorporated into such treatment strategies. In this review, I explore comprehensive treatment strategies for Hodgkin lymphoma in the early stage with both favorable and unfavorable prognosis, in the advanced stage, and relapsed or refractory disease.

Aggressive Natural Killer Cell Leukemia Secondary to Hodgkin Lymphoma: a Case Report and Review of the Literature

A 32-year old Chinese woman presented with high fever (39C), lymphadenopathy, hepatosplenomegaly, shortness of breath and general fatigue after initial remission of Hodgkin lymphoma (HL). The immuno-phenotype of blast cells found in her peripheral blood and pleural fluid suggested abnormal Natural Killer (NK) cells (CD2+CD3- CD56+CD45RO+HLADR+CD94+ with high Ki67). Her serum EB virus DNA was over 1.0×107IU/mL. Combining her clinical symptom and laboratory data, the patient was diagnosed with Hodgkin Lymphoma, secondary NK cell leukemia and haemophagocytic lymphohistocytosis (HLH). To date, this is the first reported case that developed secondary ANKL after the treatment of Hodgkin Lymphoma. Secondary treatment-related cancers are a major problem in HL survivors. Thus, novel treatment strategies for HL should aim at a reduction of chemotherapy and radiation therapy in order to reduce the risk for development of therapy-related malignancies. In conclusion, improvements of combined therapy as well as close monitoring during clinical follow up could warrant the improved overall survival of HL and prevent fatal complications.

Guest editorial: Management of malignant lymphoma is continuously improving

This issue of IJH contains four ‘‘Progress in Hematology(PIH)’’ review articles describing the management ofmalignant lymphoma, with a focus on recent clinical trials.Malignant lymphoma, characterized by its marked hetero-geneity, is the most frequent hematologic malignancy inthe world. Among the various subtypes of malignantlymphoma, the following three are clinically important:Hodgkin lymphoma, follicular lymphoma (FL), and diffuselarge B cell lymphoma (DLBCL). The current and futuremanagement of these three major subtypes are discussed byinternationally distinguished lymphoma experts who havecontributed to the establishment of the current standardmanagement of each subtype. In addition, the current andfuture management of NK/T cell lymphoma is discussed byDr. Yamaguchi, based on clinical trials recently publishedby her group.Current issues to be addressed in the management ofmalignant lymphoma differ somewhat from disease todisease. In Hodgkin lymphoma, continuous efforts toestablish more effective chemotherapy with or withoutradiotherapy have yielded high cure rates in patients withlocalized and advanced diseases. Drs. Eichenauer andEngert of the German Hodgkin Study Group (GHSG)prepared a comprehensive review article regarding thecurrent standard management, based mainly on clinicaltrials conducted by GHSG. Treatment strategies forHodgkin lymphoma are scientifically discussed, andupdated information, including that on ongoing clinicaltrials, should help readers to better understand the mostsuccessful history of using non-surgical treatment modali-ties in clinical oncology.In FL, which remains incurable in most patients, theissues are somewhat different from those in Hodgkinlymphoma. Anti-CD20 monoclonal antibodies, such asrituximab, and radioimmunotherapy have markedly pro-longed survival. In the second PIH article, Drs. Salles andGhesquie`res of Groupe d’Etudes des Lymphomes del’Adulte (GELA), which has recently been renamed theLymphoma Study Association (LYSA), summarize recentadvances in the management of patients with FL, based onthe results of recent clinical trials including the PRIMAStudy, which revealed the efficacy of maintenance use ofrituximab [1]. Considering the marked heterogeneity of FL,the prolonged median survival time probably exceeding15 years under the current treatment modalities, and theemergence of several less toxic but highly effective agents,personalized approaches will be more important in thetreatment of FL in the future.Since the establishment of rituximab plus CHOP as astandard therapy for DLBCL [2], progress has been lessremarkable. In the third PIH article in this issue,Drs. Roschewski, Dunleavy, and Wilson of the NationalCancer Institute in the United States present an excellentreview of further progress in the treatment of DLBCL. Animproved understanding of the biology of DLBCL hasrevealed a number of oncogenic driver mutations and sig-naling pathways essential for growth of the lymphoma cell.As many of these signaling pathways can be targeted bysmall molecule inhibitors, treatment of DLBCL may be instore for a paradigm shift.Finally, Dr. Yamaguchi in Japan summarizes newlydevelopedtreatmentstrategiesforNK/Tcelllymphoma,basedon the results of multicenter clinical trials. NK/T cell lym-phoma is a distinct disease subtype with dismal prognosis

Treatment strategies for Hodgkin lymphoma recurring following autologous hematopoietic stem cell transplantation

Hodgkin lymphoma (HL) represents one of the great success stories in hematology going from a uniformly fatal disease, to one that is curable in the vast majority of cases. Despite this success, some patients experience relapse. To address this unmet need a variety of agents, classes of drugs, and strategies have demonstrated activity in HL recurring after autologous hematopoietic stem cell transplantation. These include chemotherapeutics (gemcitabine-based combinations, bendamustine), histone deacetylase (HDAC) inhibitors (panobinostat), immunomodulatory agents (lenalidomide), mTOR inhiobitors (everolimus), monoclonal antibodies (rituximab), and antibody-drug conjugates (brentuximab vedotin) as well the potential of long-term disease control via allogeneic transplantation. Such advances reflect our increased understanding of the biology of HL and hold promise for continued improved outcomes for those suffering with this condition.

BEACOPP chemotherapy is a highly effective regimen in children and adolescents with high-risk Hodgkin lymphoma: a report from the Children's Oncology Group

AbstractDose-intensified treatment strategies for Hodgkin lymphoma (HL) have demonstrated improvements in cure but may increase risk for acute and long-term toxicities, particularly in children. The Children's Oncology Group assessed the feasibility of a dose-intensive regimen, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) in children with high-risk HL (stage IIB or IIIB with bulk disease, stage IV). Rapidity of response was assessed after 4 cycles of BEACOPP. Rapid responders received consolidation therapy with guidelines to reduce the risk of sex-specific long-term toxicities of therapy. Females received 4 cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine) without involved field radiation therapy (IFRT). Males received 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) with IFRT. Slow responders received 4 cycles of BEACOPP and IFRT. Ninety-nine patients were enrolled. Myelosuppression was frequent. Rapid response was achieved by 74% of patients. Five-year event-free-survival is 94%, IFRT with median follow-up of 6.3 years. There were no disease progressions on study therapy. Secondary leukemias occurred in 2 patients. Overall survival is 97%. Early intensification followed by less intense response-based therapy for rapidly responding patients is an effective strategy for achieving high event-free survival in children with high-risk HL. This trial is registered at http://www.clinicaltrials.gov as #NCT00004010.

Gemcitabine and Other New Cytotoxic Drugs: Will Any Find Their Way Into Primary Therapy?

Primary treatment for classic Hodgkin lymphoma (HL) remains highly effective with chemotherapy alone or combined-modality therapy. The limitations of therapy have been related to toxicity and efficacy in subsets of patients. The introduction of a number of new and novel cytotoxic agents has provided opportunities for investigating their use in the treatment of HL. This article briefly reviews current primary treatment strategies for HL and examines the existing data for both new cytotoxic agents and other selected novel agents in the treatment of HL.

A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425

AbstractCurrent treatment strategies for Hodgkin lymphoma result in excellent survival but often confer significant long-term toxicity. We designed ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide) to (1) enhance treatment efficacy by dose-dense drug delivery and (2) reduce risk of long-term sequelae by response-based reduction of cumulative chemotherapy. Efficient induction of early response by dose-dense drug delivery supported an early-response–adapted therapeutic paradigm. The 216 eligible patients were younger than 22 years with intermediate- or high-risk Hodgkin lymphoma. ABVE-PC was administered every 21 days. Rapid early responders (RERs) to 3 ABVE-PC cycles received 21 Gy radiation to involved regions; RER was documented in 63% of patients. Slow early responders received 2 additional ABVE-PC cycles before 21 Gy radiation. Five-year event-free-survival was 84%: 86% for the RER and 83% for the slow early responders (P = .85). Only 1% of patients had progressive disease. Five-year overall survival was 95%. With this regimen, cumulative doses of alkylators, anthracyclines, and epipodophyllotoxins are below thresholds usually associated with significant long-term toxicity. ABVE-PC is a dose-dense regimen that provides outstanding event-free survival/overall survival with short duration, early-response–adapted therapy. This trial was registered at www.clinicaltrials.gov as #NCT00005578.