Ádám Jóna

Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma

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

Brentuximab vedotin for treating Hodgkin’s lymphoma: an analysis of pharmacology and clinical efficacy

Introduction: Hodgkin’s lymphoma (HL) is a highly curable lymphoma with a 70 – 90% long-term survival; however, patients with relapsed or refractory disease may need additonal therapies and have significantly worse prognosis. Brentuximab vedotin (BV) is an anti-CD-30 antibody-drug conjugate, which was approved for treating classical HL patients following autologous stem cell transplantation or failure of at least two prior multi-agent chemotherapies within a year. Areas covered: Current clinical trials are investigating the role of BV in frontline, salvage and adjuvant setting of treatment. Safety and efficacy results of completed trials are summarized in this review. Metabolic, pharmacokinetic issues of BV are also discussed. Expert opinion: BV is a targeted therapeutic option for treating HL, which is a significant improvement compared to conventional multiagent chemotherapy. It may represent a valid option for heavily pretreated patients. Currently running clinical trials are seeking a role for BV in the first-line setting, as well as treating autologous stem cell transplant candidate patients, relapsing after autologous stem cell transplant, bridging to allogenic stem cell transplant and treating elderly patients. Indication of drug may change, expand and an exact role may be established in the upcoming 5 years based on the results of currently running trials.

Immunologic pathomechanism of Hodgkin's lymphoma

Hodgkins lymphoma is a lymphoid malignancy of the immune system. The pathognomonic Hodgkin and Reed-Sternberg cells (HRS) are derived mainly from monoclonal, preapoptotic B cells, and they carry rearranged, somatically mutated immunoglobulin heavy chains. In an appropriate microenvironment, HRS cells escape from apoptosis by several mechanisms, including single mutations, aberrant signaling pathways. Eventually, weakened immune surveillance leads to uncontrolled, disproportional B cell proliferation. This review summarizes the latest findings on the pathogenesis of Hodgkin lymphoma, with a special emphasis on immunologic processes, and depicts current and future immunotherapeutic regimens, which improve treatment outcomes and reduce late toxicities.

Late pulmonary complications of treating Hodgkin lymphoma: bleomycin-induced toxicity.

Introduction: Survival of Hodgkin lymphoma (HL) patients has significantly improved in recent decades. The current first-line therapy is doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) ± irradiation and may cause pulmonary toxicity. Strategies to reduce late toxicity as well as increase survival rate are of interest. Patients and methods: Pulmonary function of previously treated HL patients was collected over a 12-month period using St. George Respiratory Questionnaire (SGRQ), chest X-ray, dynamic inhalation lung scintigraphy and spirometry. Results: A total of 137 patients’ data were reviewed. Median time elapsed since diagnosis was 11 years (range was 2 – 30 years). Chest irradiation did not significantly worsen pulmonary function. Number of ABVD cycles with consequential bleomycin dose showed significant correlation with SGRQ total score in patients receiving ABVD plus chest irradiation (p = 0.01). Scintigraphy results correlated with bleomycin dose in patients receiving ABVD without chest irradiation (right side: p = 0.099, left side: p = 0.051). Discussion: An additive negative effect of chest irradiation was not confirmed as reflected in the literature; however, increasing cumulative bleomycin dose worsened pulmonary function.

Effect of Bleomycin Hydrolase Gene Polymorphism on Late Pulmonary Complications of Treatment for Hodgkin Lymphoma

Background Bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, may be a potential candidate that could influence pulmonary function in ABVD (doxorubicin, bleomycin, vinblastin, dacarbasine)–treated Hodgkin lymphoma (HL) patients. Patients and Methods We hypothesized that the BLMH gene SNP A1450G (rs1050565) influences BLMH activity and late pulmonary toxicity. St. George Respiratory Questionnaire, lung scintigraphy and spirometry were used to determine lung function. TaqMan genotyping assay was used to determine genotype distribution of 131 previously treated HL patients. Results Significantly more favorable results were seen in the wild-type A/A genotype group than those in the group containing the mutated allele: A/G+G/G in retrospective pulmonary tests of ABVD treated patients. Conclusion Besides limitations of the current study, bleomycin pharmacokinetics should be further evaluated in patients with BLMH variations, hence identify those cases even in the frontline setting, where bleomycin should be omitted and replaced with targeted therapy.

Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

Absztrakt Bevezetes: A Hodgkin-lymphoma 80–90%-ban gyogyithato, azonban a betegek korulbelul 30%-a relabal, es csak ezeknek a betegeknek a feleben erhető el gyogyulas autolog őssejt-transzplantacio alkalmazasaval. Celkitűzes: 1980. januar 1. es 2014. december 31. kozott kezelt es gondozott Hodgkin-lymphomas betegek tulelesi adatainak, a relapsusok gyakorisaganak elemzese, az uj terapias lehetősegek bemutatasa. Modszer: A betegek adatainak retrospektiv elemzese. Eredmenyek: Osszesen 715 beteget kezeltek (382 ferfi es 333 nő, atlageletkoruk a betegseg diagnosztizalasakor 38 ev). A relabalo betegek aranya a legutolso időszakban 24,87%-rol 8,04%-ra csokkent. Az elvegzett autolog haemopoeticus transzplantaciok szama a relabalo/refrakter betegek kozott nőtt, 2000-től kezdve 75%-ot ert el. A teljes tuleles szignifikansan javult; az 5 eves teljes tuleles 1980–1989 kozott 64,4%, 1990–1999 kozott 82,4%, 2000–2009 kozott 88,4%, 2010–2014 kozott 87,1% volt. A relapsusmentes tuleles nem mutatott szignifikans valtozast...

Diagnostic difficulties caused by a pulmonary infiltrate

UNLABELLED Lung infiltration still causes differential diagnostic difficulties, which may delay the start of definitive treatment. CASE REPORT The examination of a 30-year-old man began due intermittent, remittent and permanent fever. Chest X-ray confirmed infiltration in the right upper lobe, which was accompanied by elevated CRP and physiological levels of procalcitonin. Most likely atypical pneumonia, tuberculosis, Wegeners granulomatosis or a malignant process was suspected. Throughout his examination infection could not be verified, repeated CT guided transthoracic needle biopsy suggested the possibility of a malignant process. Through surgical exploration the intraoperative histology was not informative; thus, the pneumonitis-remodelled right lung was removed due to the possibility of malignant transformation. Histological examination revealed lymphocyte rich classical Hodgkin lymphoma, which was found to be stage IV/B based on the 18FDG-PET/CT scan; therefore, eight cycles of ABVD (adriablastin, bleomycin, vinblastine, and dacarbazine) therapy was administered successfully. The patient is currently (for 30 months) in a complete metabolic remission. CONCLUSION Primary pulmonary Hodgkin lymphoma is a rare disease entity (in this case it might be the original process), in which the diagnosis is often difficult. 18FDG-PET/CT may be a useful early diagnostic tool investigating fever of unknown origin.

Primer központi idegrendszeri diffúz nagy B-sejtes lymphoma relapszus sikeres kezelése

Absztrakt: Bevezetes: A primer kozponti idegrendszeri diffuz nagy B-sejtes lymphoma ritka betegseg. Az első vonalbeli autolog transzplantacioval elert biztato eredmenyek ellenere a relabalo betegek...

Így kezeljük az autológ őssejt-transzplantáció után kiújult Hodgkin-lymphomát

Absztrakt: Az elsődleges kezeles utan a Hodgkin-lymphomas betegek 10–30%-a relabal vagy refrakter. Jelenleg elsőkent autolog haemopoeticus őssejt-transzplantacio javasolt ezekben az esetekben, bar ezt kovetően csak a betegek fele gyogyul meg, a median teljes tuleles is mindossze 2–2,5 ev. Szamos prognosztikai tenyező hatarozza meg az autolog haemopoeticus őssejt-transzplantacio sikeresseget, amelyek figyelembevetelevel, szukseg eseten konszolidacios kezeles alkalmazasaval az eredmenyek javithatok. Az autolog őssejt-transzplantacio utan relabalo betegeknek meg kedvezőtlenebb a tulelese, es ennek a betegcsoportnak a kezelese jelenti a legnagyobb kihivast a Hodgkin-lymphoma terapiaja soran. Szerencsere az utobbi evekben szamos uj kezelesi mod valt elerhetőve, igy a brentuximab vedotin es az immuncheckpoint-gatlok, amelyektől a tulelesi es gyogyulasi eredmenyek javulasat remeljuk. Az allogen transzplantacio eredmenyei is javulhatnak a haploidentikus transzplantacio alkalmazasaval. Osszefoglalonkban ezeket az ...

Rapidly Progressing Refractory Hodgkin Lymphoma: A Case Report and a Possible Explanation

Introduction. Hodgkin lymphoma is a highly curable lymphoid malignancy; however treatment of a significant number of patients remains challenging. Case Report. The authors present an unusually rapidly progressing case of refractory advanced stage classical nodular sclerosis subtype Hodgkin lymphoma with unfavorable prognosis. A 66-year-old male patient was refractory for first-line doxorubicin, bleomycin, vinblastin, dacarbazine (ABVD) treatment with persistent disease; therefore physicians changed treatment for dexamethasone, cytarabine, and cisplatin (DHAP) and later ifosfamide, gemcitabine, and vinorelbine (IGEV) regimen. Unfortunately the patient developed acute kidney and respiratory failure and died after 6 months of treatment. Current and retrospective histological examination of the patients lymph node biopsy, skin lesion, and autopsy revealed the same aberrantly expressing CD4 positive nodular sclerosis subtype Hodgkin lymphoma. Conclusion. Aberrant expression of T-cell antigens on the Hodgkin and Reed/Sternberg cells could be associated with inferior outcome. T-cell associated antigens should be investigated more often in patients not responding sufficiently to treatment and hence treatment should be intensified or targeted therapy (brentuximab vedotin) should be considered.