[PET-CT documented remission of multicentric Castleman disease after treatment with rituximab: case report and review]. / PET-CT dokumentovaná remise multicentrické formy Castlemanovy choroby po lécbe rituximabem Popis prípadu a prehled literatury.

We describe a case of multicentric Castleman disease with generalized lymphadenopathy and splenomegaly, accompanied by typical B symptoms - loss of 15 kg, fever of non-infectious origin, night sweats, symptoms of anemia. Histological examination of the nodes with the highest accumulation of fluorodeoxyglucose, taken from mediastinum by thoracoscopy, revealed plasmocellular type of Castleman disease. Tests for HIV and human herpesvirus 8 (HHV-8) were negative. Three recurrences of herpes zoster indicating an alteration of immunity preceded the dia-gnosis of disease. Treatment was initiated with combination of thalidomide, dexamethasone, and cyclophosphamide. The response after 2 months therapy was not clear and patient doesn't tolerated the therapy well. Therefore, this treatment was terminated and R-CHOP (Mabthera - rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone) was selected as a second-line therapy. Lymphadenopathy and splenomegaly were reduced during the 2 cycles of treatment, however, serious infectious complications accompanied the therapy. Therefore, only use of Mabthera monotherapy 375 mg /m2 was administered in 28-day intervals. This treatment has shown efficacy and tolerability. PET-CT scan has demonstrated disappearance of lymphadenopathy and splenomegaly, in addition, normalized accumulation of fluorodeoxyglucose. Monotherapy with Mabthera has proved to be effective and well tolerated drug in this case. Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). In the case of ineffectiveness of one treatment option must be tested other alternative. In this case the therapy based on thalidomide wasn't successful, whereas the treatment with Mabthera has achieved disappearance of disease symptoms.

Significant current epidemiological trend: Haematological malignancies as subsequent primary tumours in cancer patients.

BACKGROUND: Numbers of patients who develop subsequent primary tumours have markedly increased recently. This study aimed to carry out a comprehensive analysis documenting the risk of incidence of subsequent haematological malignancies. METHODS: The Czech National Cancer Registry was the main data source, containing records of 126,822 haematological malignancies diagnosed in the period 1977-2016. Subsequent haematological malignancies were identified according to IACR rules. Joinpoint regression was employed to assess the time trends. The risk of development of subsequent haematological malignancy was evaluated by the standardised incidence ratio. The Kaplan-Meier curves were used to assess the differences in survival. RESULTS: Age-standardised incidence of subsequent haematological malignancies increased from 0.5 in 1977 to 9.1 in 2016. In 1992, there was a significant change in the trend: a sharp increase by 7.7 % annually was revealed thereafter. The risk of development of a haematological malignancy was approximately 1.5 times higher in persons with history of any cancer than in the general Czech population. Patients with haematological malignancies - mainly myelodysplastic syndromes, polycythaemia vera and non-Hodgkin lymphoma - were shown to be at the highest risk of developing a subsequent haematological malignancy. While the median survival following a first haematological malignancy was 2.3 years, it was only 1.1 years for subsequent haematological malignancies (p < 0.001). CONCLUSIONS: Our study identified the highest-risk diagnoses in terms of development of subsequent haematological malignancy. The results might be useful to set up correctly follow-up procedures from which cancer patients could benefit.

Cardiopulmonary exercise testing in the evaluation of functional capacity after treatment of lymphomas in adults.

The present study assessed several parameters of cardiopulmonary function in patients, after treatment for aggressive non-Hodgkin's lymphoma and Hodgkin's disease, to determine the influence of these parameters on patient's performance status. One hundred and six patients (66 male and 40 female) aged 40 +/- 15 years were examined 1-2 years (median 14 months) after anticancer treatment. The patients were examined by means of rest and dynamic stress echocardiography and cardiopulmonary exercise. The rest and post-exercise ejection fraction (EF), Doppler parameters of left ventricular diastolic function and peak oxygen consumption (pVO2) were used as parameters of cardiopulmonary performance. The cumulative dose (CD) of doxorubicin (DOX) given was 240 +/- 70 (240 mg/m2). Thirty-seven percent of patients received mediastinal irradiation in accordance with the used treatment protocol. Sixty-four patients (60%) experienced fatigue after the treatment. Three patients (3%) demonstrated an decreased EF <50%, 34 (32%) demonstrated impaired diastolic function, 14 (13%) demonstrated decreased pVO2<20 ml/kg/min and 15 (14%) demonstrated a value of pVO2 below the reference value, respectively. None of the patients exhibited clinical signs of heart failure. Apart from three patients with a rest EF<50%, all the other patients responded to stress echocardiography with an increment of EF > 5%. The parameter pVO2 significantly correlated with stress EF (0.58, P < 0.0002). A significant relationship was found with all parameters of diastolic function: to index E/A of diastolic filling (r = 0.67, P < 0.0001), isovolumic relaxation time (r = -0.56, P < 0.0009) and to deceleration time (r = -0.54, P < 0.009), respectively. A negative relationship was found with age (r = -0.74, P < 0.0001), CD of DOX (r = -0.53, P < 0.003) and radiotherapy-involving mediastinum (r = - 0.44, P < 0.04), respectively. Using multivariate analysis, a significant relationship was found between pVO2 and parameters of diastolic filling, age, female sex and CD of DOX, respectively (r = 0.58, P < 0.0001). Diastolic dysfunction was correlated with age, CD of DOX and radiotherapy-involving mediastinum, respectively (r = 0.51, P < 0.01). The results show that diastolic dysfunction was the most affected parameter of cardiopulmonary function in cancer survivors. This parameter negatively influenced cardiopulmonary performance and was significantly correlated with the cumulative dose of doxorubicin given and radiotherapy on mediastinum. Despite a high number of patients experiencing fatigue, the study demonstrates that only a relatively small number of patients show a depressed pVO2 on a cardiopulmonary stress test and other cardiac abnormalities. The results of the tests support the introduction of regular aerobic exercise for cancer survivors to increase their cardiopulmonary performance and well-being. Hypothetically, aerobic training may also positively influence diastolic function. However, this assumption warrants a prospective follow-up.

Prognostic relevance of DHAP dose-density in relapsed Hodgkin lymphoma: an analysis of the German Hodgkin-Study Group.

Only 50% of patients with relapsed Hodgkin lymphoma (HL) can be cured with intensive induction chemotherapy, followed by high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). Based on the results of the HDR2 trial two courses of DHAP and subsequent HDCT/ASCT are the current standard of care in relapsed HL. In order to assess the prognostic relevance of DHAP dose density, we performed a retrospective multivariate analysis of the HDR2 trial (N=266). In addition to four risk factors (early or multiple relapse, stage IV disease or anemia at relapse, and grade IV hematotoxicity during the first cycle of DHAP) a delayed start of the second cycle of DHAP>day 22 predicted a significantly poorer progression-free survival (PFS, p=0.0356) and overall survival (OS, p=0.0025). In conclusion, our analysis strongly suggests that dose density of DHAP has a relevant impact on the outcome of relapsed HL patients.

Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group.

PURPOSE: Eight cycles of BEACOPP(escalated) (escalated dose of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by radiotherapy (RT) to initial bulk or residual tumor mass is the German Hodgkin Study Group standard of care for advanced-stage Hodgkin's lymphoma (HL). However, treatment-related toxicity is a concern, and the role of RT in this setting is unclear. The HD12 study thus aimed to reduce toxicity while maintaining efficacy. PATIENTS AND METHODS: In this prospectively randomized multicenter trial, eight cycles of BEACOPP(escalated) was compared with four cycles of BEACOPP(escalated) followed by four cycles of the baseline dose of BEACOPP (BEACOPP(baseline); 4 + 4), and RT with no RT in the case of initial bulk or residual disease. The study was designed to exclude a difference in 5-year freedom from treatment failure (FFTF) rate of 6%. RESULTS: Between January 1999 and January 2003, 1,670 patients age 16 to 65 years were enrolled onto the HD12 study. At 5 years, FFTF was 86.4% in the BEACOPP(escalated) arm and 84.8% in the 4 + 4 arm (difference, -1.6%; 95% CI, -5.2% to 1.9%), and overall survival was 92% versus 90.3% (difference, -1.7%; 95% CI, -4.6% to 1.1%). Deaths related to acute toxicity of chemotherapy were observed in 2.9% of patients (BEACOPP(escalated), n = 19; 4 + 4, n = 27). FFTF was inferior without RT (90.4% v 87%; difference, -3.4%; 95% CI, -6.6% to -0.1%), particularly in patients who had residual disease after chemotherapy (difference, -5.8%; 95% CI, -10.7% to -1.0%), but not in patients with bulk in complete response after chemotherapy (difference, -1.1%; 95% CI, -6.2% to 4%). CONCLUSION: The reduction of BEACOPP to the 4 + 4 regimen did not substantially reduce severe toxicity but might decrease efficacy. Our results do not support the omission of consolidation RT for patients with residual disease. Alternative strategies for improving the risk-to-benefit ratio for patients with advanced HL are needed.

Dose intensity of chemotherapy in patients with relapsed Hodgkin's lymphoma.

PURPOSE: High-dose chemotherapy (HDCT) followed by autologous stem-cell transplantation (PBSCT) has become the standard treatment for patients with relapsed Hodgkin's lymphoma (HL). The intensity of treatment needed is unclear. This European intergroup study evaluated the impact of sequential high-dose chemotherapy (SHDCT) before myeloablative therapy. PATIENTS AND METHODS: Patients with histologically confirmed, relapsed HL were treated with two cycles of dexamethasone, cytarabine, and cisplatin, and those without disease progression were randomly assigned. In the standard arm (A), patients received myeloablative therapy with carmustine, BEAM (carmustine, etoposide, cytarabine, and melphalan) followed by PBSCT. Patients in the experimental arm (B) also received sequential cyclophosphamide, methotrexate, and etoposide in high-doses before BEAM. Freedom from treatment failure (FFTF) was the primary end point. Remission rates, overall survival (OS), and toxicity of treatment were secondary end points. RESULTS: From a total of 284 patients included, 241 responding patients were randomly assigned after two cycles of dexamethasone, cytarabine, and cisplatinum. Patients treated in arm B had longer treatment duration and experienced more toxicity and protocol violations (P < .05). Mortality was similar in both arms (20% and 18%). With a median observation time of 42 months, there was no significant difference in terms of FFTF (P = .56) and OS (P = .82) between arms. FFTF at 3 years was 62% (95% CI, 56% to 68%) and OS was 80% (95% CI, 75% to 85%). Patients with stage IV, early relapse, multiple relapse, anemia, or B symptoms had a higher risk of recurrence (P < .001). CONCLUSION: Compared with conventional high-dose chemotherapy, additional SHDCT is associated with more adverse effects and does not improve the prognosis of patients with relapsed HL.

Successful treatment of steroid-refractory hepatitic variant of liver graft-vs-host disease with pulse cyclophosphamide.

OBJECTIVE: Corticosteroid-resistant graft-vs-host disease (GVHD) is difficult to manage and is associated with high morbidity and mortality. No standard treatment exists. We have previously seen good results with pulse cyclophosphamide (Cy) in the treatment of liver GVHD in contrast to gastrointestinal GVHD, and here we report results of pulse Cy protocol in the treatment of steroid-refractory hepatitic variant of liver GVHD, with no association to the gut. MATERIALS AND METHODS: Cy was infused at a dose of 1,000 mg/m(2). Twenty-nine cyclophosphamide administrations were given to 21 patients. Median time of GVHD onset and Cy administration after transplantation, or donor lymphocyte infusion, were 58 and 69 days, respectively. RESULTS: Eleven patients (52%) achieved complete remission and 6 patients (29%) achieved partial remission. Four patients (19%) did not respond, however, their condition stabilized and, upon additional therapy, three achieved partial remission and one complete remission. Overall survival of all 21 patients is 86%, with median and maximal follow-up of 33 and 81 months, respectively. Toxicity was mild and easily manageable without influencing chimerism or disease status. CONCLUSIONS: Pulse Cy seems to be an effective treatment for steroid-refractory hepatitic variant of liver GVHD with a good toxicity profile, which may favor its use instead of drugs with more pronounced immunosuppressive effects.