Lenka Šmardová

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 Hodgkins 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.

Prevention of ovarian function damage by a GnRH analogue during chemotherapy in Hodgkin lymphoma patients

BACKGROUND Frequent negative consequence of chemotherapy (CHT) is ovarian damage and premature ovarian failure (POF). Aim of this prospective case-control study is evaluation of GnRH analogue (GnRH-a) administration to patients with Hodgkin lymphoma (HL) during CHT and prevention of ovarian damage depending upon CHT regimen. METHODS Study group consists of 72 patients in fertile age (18-35 years) with HL diagnosis treated in 2004-2005 by curative CHT together with GnRH analogue (Triptorelin) administration according to a standardized protocol. Patients were divided into three groups according to the stage of disease and treated by three types of CHT regimens (A,B,C) with increased cytotoxicity. Ovarian function of all patients was assessed by gonadotrophin levels (FSH, LH) analysis from peripheral blood before treatment and also 6 and 12 month after it. The number of women with POF after CHT in study group was compared with control group (n = 45, age 18-35 years) of patients treated in 2002-2003 according to the same protocol but without protective GnRH analogue application. RESULTS In study group with GnRH analogue administration during CHT, there was significantly (P < 0.001) fewer cases with POF 6 and 12 month after the end of CHT (37.5% and 20.8%, respectively) than in control group (73.3% and 71.1%, respectively). Comparative analysis depending on cytotoxicity of CHT regimen used showed significant differences in percentage of patient with acquired POF between study and control group only in less aggressive CHT protocols. CONCLUSIONS Study showed a significant reduction of ovarian failure risk in women with HL treated with less aggressive CHT regimens plus a GnRH analogue.

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-Hodgkins lymphoma and Hodgkins disease, to determine the influence of these parameters on patients 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.

Successful mobilization of peripheral blood stem cells with the DHAP regimen (dexamethasone, cytarabine, cisplatinum) plus granulocyte colony-stimulating factor in patients with relapsed Hodgkin's disease

High-dose chemotherapy followed by autologous stem cell transplantation can improve the outcome of relapsed and refractory Hodgkins disease (HD) patients. The objective of the trial was to determine the mobilizing potential of the DHAP salvage regimen (dexamethasone, cytarabine, cisplatin) for the collection of peripheral blood stem cells (PBSC) in patients with relapsed HD. The target yield of harvesting CD34 + cells was > or =2 x 10(6)/kg in order to support the subsequent myeloablative chemotherapy. Most of the 105 patients included were intensively pre-treated with different combination chemotherapy regimens prior to mobilization. The use of DHAP followed by granulocyte colony-stimulating factor (G-CSF; 10 microg/kg) resulted in the successful collection of adequate numbers of PBSC in 97.1% of patients (102 of 105) with a median harvest of CD34+ cells of 13 x 10(6)/kg (range 2.6 - 85.1). More than 2.0 x 10(6) CD34+ cells/kg were achieved in 65 of 103 (63%) patients after 1 apheresis, the maximum number of aphereses for all patients was 3. It was found that the optimal time of PBSC harvest was at days 13 - 16 after initiating the mobilization regimen. These results demonstrate that the salvage chemotherapy regimen, such as DHAP combined with G-CSF, can be successfully used to mobilize PBSC in HD patients.

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.

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

Abstract 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.