Fertility status of Hodgkin lymphoma patients treated with chemotherapy and adjuvant gonadotropin-releasing hormone analogues.

PURPOSE: Aim of this prospective observational study was to analyze fertility status of Hodgkin lymphoma (HL) patients treated with different types of chemotherapy while receiving GnRH analogues to preserve ovarian function. METHODS: Fertility status was assessed among 108 females in reproductive age treated by curative chemotherapy for freshly diagnosed HL between 2005 and 2010 in university-based tertiary fertility and oncology center. All patients received GnRH analogues during chemotherapy to preserve their ovarian function. Their reproductive functions were assessed by follicle-stimulating hormone (FSH) measurement and pregnancy achievement. Ovarian function was determined separately in three groups with increasing gonadotoxicity of chemotherapy. RESULTS: One year following the treatment, normal ovarian function was found in 89 (82.4%) of patients. Two years after chemotherapy, 98 (90.7%) of patients retained their ovarian function, and 23 (21.3%) achieved clinical pregnancy during the follow-up period. Average FSH after chemotherapy was 11.6 ± 17.9 IU/l 1 year after the treatment resp. 9.0 ± 13.8 at the 2 years interval. There were significantly more patients with chemotherapy induced diminished ovarian reserve (chDOR) among the group receiving escalated BEACOPP chemotherapy in comparison with the other types of treatment (58.1% vs. 87.9% resp. 95.5%). CONCLUSION: The rate of chDOR is significantly higher after EB poly-chemotherapy and there is no tendency for improvement in time. The 2 + 2 chemotherapy with GnRH-a required for more advanced HL retained ovarian function significantly better after 2 years. Another important advantage of GnRH-a co-treatment is the excellent control of patient's menstrual cycle.

[Castleman disease: retrospective single-center study of therapeutic results in 10 patients]. / Castlemanova choroba: retrospektivní studie lécebných výsledku u 10 pacientu z jednoho centra.

BACKGROUND: Castleman disease is a non-clonal lymphoproliferative disorder with 2 clinical (unicentric, multicentric) and 4 histomorphological (hyaline vascular, plasma cell, mixed, plasmablastic) forms which combine creating a pleomorphic picture of this rare entity. In our work, the largest documented cohort in the Czech Republic was analyzed focusing on diagnostics and particularly on therapy. PATIENTS AND METHODS: The retrospective study (1998-2013) included 10 patients, 6 males, 4 females. Patients with unicentric form (3) underwent surgical sanitation. Patients with multicentric form (7) were followed-up only (2) or extirpation of the largest mass was carried out (1) or a systemic therapy was administered (4) which comprised the following regimens: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), CTD/CAD/CVD (cyclophosphamide, thalidomide/adriamycin/bortezomib, dexamethasone), further including monotherapies with tocilizumab, thalidomide and lenalidomide and in one case (associated POEMS syndrome, i.e. polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) autologous stem cell transplantation after melphalan conditioning was performed. During treatment response monitoring, all patients underwent PET/CT examination (fluorodeoxyglucose positron emission tomography/computed tomography). RESULTS: The remission rate was 50% (3 unicentric forms with remission lasting 51, 8 and 9 months, resp.; 2 multicentric forms with remission lasting 3 months during thalidomide therapy and 12 months after lenalidomide therapy), stable disease was observed in 40% of cases (multicentric forms, 2 without any treatment followed-up for 171 and 24 months, resp.; 1 after systemic therapy followed-up for 23 months; 1 after two extirpations with stable lymphadenopathy for 15 years, where the first operation was 27 years ago). In one patient (10%), the associated POEMS syndrome progressed rapidly with fatal consequences (4 months follow-up). CONCLUSION: Unlike unicentric forms completely curable by excision, multicentric forms are often treatment-refractory. Concerning high cost-effectiveness, good tolerability and documented efficacy also in rituximab-resistant cases, we prefer immunomodulatory drugs (particularly thalidomide) for managing multicentric Castleman disease in our center.

[Our experience in treatment of multicentric plasma-cell Castleman disease associated with vasculitis manifestations - case report and literature review]. / Nase zkusenosti s lécbou multicentrické plazmocelulární Castlemanovy choroby s projevy vaskulitidy - popis prípadu a prehled literatury.

Castleman disease is a rare idiopathic non-neoplastic lymphoproliferative disorder with 2 clinical (unicentric and multicentric) and 3 histomorphological (hyaline-vascular, plasma-cell and mixed) forms identified. The case report given here describes the 3-year experience with therapy in a patient, male born 1961, diagnosed with multicentric plasma-cell Castleman disease (HIV and HHV-8 negative) with the finding of generalized lymphadenopathy and splenomegaly. During first line treatment (R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, 3 cycles in total, 12/2008-2/2009) the development of bilateral upper and lower limb edemas with clinical manifestation of vasculitis occurred and a restaging computed tomography (CT) examination revealed a stable finding of the lymphadenomegaly. Greater success was achieved with thalidomide regimen (CTD: cyclophosphamide, thalidomide, dexamethasone, 10 cycles, 3/2009-1/2010) leading to reduction in the size of the hypervascularized lymph nodes (almost by 50%) as well as their radiopharmaceutical (fluorodeoxyglucose) uptake as seen on a combined positron emission tomography and computed tomography (PET/CT) scan imaging. Thalidomide was given daily at doses between 100 and 200 mg. We returned to the CTD regimen again in April 2010 after a short period of monoclonal antibody tocilizumab treatment (400 mg intravenous in 2-week intervals with 50% dose reduction due to a limited supply of the drug, 5 doses in total) during which edemas reoccurred with a CT scan finding of stable lymphadenomegaly. However, the renewed regimen with thalidomide was stopped after 2.5 cycles due to adverse effects of thalidomide (neuropathy) and corticoids (Cushing syndrome). In September 2010, after enrollment in the Celgenes Compassionate Use Program we were able to start treating the patient with the derivative of thalidomide, lenalidomide, at a dosage of 25 mg on days 1-21 in a 28-day cycle, 15 cycles in total (10/2010-12/2011). The monotherapy with lenalidomide was very well tolerated by the patient without any effects of myelotoxicity, thromboembolism or relapses of edemas and vasculitis, additionally now with apparent improvement of fatic disorder and the patients motor abilities. Thus, lenalidomide represents an attractive alternative agent for patients with Castleman disease after rituximab and cytostatics failures. It has a favourable safety profile and could be therefore considered for administering in first line treatment.

[Ovarian tissue cryopreservation in cancer patients--six years of clinical experience]. / Kryokonzervace ovariální tkáne u onkologických pacientek--6 let klinických zkuseností.

OBJECTIVE: Presentation of clinical results and experience with this technique during past six years. DESIGN: Original paper. SETTINGS: Gynekologicko-porodnická klinika LF MU a FN Brno, Interní hemato-onkologická klinika LF MU a FN Brno, Department of Obstetrics and Gynecology. Hadassah University Hospital Ein-Karem, Jerusalem, Izrael. INTRODUCTION: Ovarian tissue cryopreservation (OTC) and its future auto-transplantation becomes an alternative for patients to prevent serious damage of ovarian function by oncology treatment. METHODS: Patient is indicated to OTC in case of high risk of ovarian failure due to planned chemotherapy and impossibility to use other oncofertility techniques. Ovarian tissue harvesting is done by laparoscopy in short-term general anesthesia. After tissue processing the samples are cryopreserved in programmable automatic freezer or by vitrification. The auto-transplantation of ovarian tissue is planned after the complete cure of patient's malignancy. Our workplace doesn't have own experience with tissue transplantation - until now cryopreserved tissue has not yet been utilized by the patients. Clinical experience with this technique gained by our team during academic stay in abroad Israeli clinic is presented. RESULTS: During the years of 2005-2011 the OTC was performed in 19 cancer patients before chemotherapy. In majority of cases, patients suffered from blood or lymph node systemic malignancy (84%). Average age of women was 26 years. The patient set consisted of mostly nulliparous women (88%). Patient's average body mass index was 23,9 kg/m2. The length of systemic chemotherapy averaged 7.1 months. Time from fertility preservation counseling to chemotherapy was not exceeding one week (7.2 days on average). Ovarian tissue harvesting was conducted by laparoscopic surgery in all cases. The length of surgery did not exceed 60 minutes and no surgical complications were observed. The case of ovarian tissue transplantation performed on abroad university settings is discussed. CONCLUSION: In the consensus of with international guidelines OTC is offered to patients with high risk of ovarian failure doe to cytotoxic oncology treatment. Research in the field of oncofertility is focused on the techniques of in-vitro folliculogenesis in retrieved ovarian tissue.

Combination of fertility preservation strategies in young women with recently diagnosed cancer.

BACKGROUND/AIMS: The study describes clinical management and outcomes of currently available fertility preservation techniques in a set of 154 young female cancer patients. METHODS: Patients in reproductive age with newly diagnosed cancer were offered embryo or oocyte cryopreservation, ovarian tissue cryopreservation and the administration of GnRH analogues during chemotherapy. Particular attention was given to the technical aspects and clinical application of these fertility preservation techniques. RESULTS: During the study period (2004-2009), 154 young female cancer patients were offered fertility preservation counseling. Patient's average age was 29.4 years and average parity was 0.7 children. Administration of GnRH analogues (n = 123, 79.9%) and ovarian tissue cryopreservation (n = 15, 9.7%) were the most commonly used fertility preservation strategies. In 20 cases (16.1%), the combination of several fertility preservation techniques was offered to individually selected patients. CONCLUSIONS: Combination of fertility preservation techniques gives young cancer patients the best chance for future fertility and should be concentrated in specialized centers.

[Impact of oncological treatment on human reproduction]. / Vliv onkologické lécby na lidskou reprodukci.

Infertility is one of the most common permanent implications of oncology treatment of patients in reproductive age. The aim of this paper is to summarize current knowledge about the impact of basic modalities of oncology treatment on human reproduction. The authors describe the influence of chemotherapy, radiotherapy and pelvic surgery on the reproductive functions of men and women. Both chemotherapy and radiotherapy diminish the ovarian reserve of follicles, which is the main determining factor of premature ovarian failure. Modern markers of ovarian reserves are introduced, which in common clinical practice can effectively help to evaluate the risk of irreversible damage to the gonadal cells done by oncological disease or its curative treatment. If there is a good chance to permanently cure malignant disease in an oncological patient of fertile age, it is advisable to consider new modern techniques of reproductive protection in cooperation with reproductive medicine specialists.

[Lymphoma-like course in aggressive adult multisystem Langerhans cell histiocytosis and the benefit of PET/CT imaging in evaluation of diffuse metabolic activity of lung parenchyma]. / Lymfomu podobný prubeh agresivní multisystémové histiocytózy z Langerhansoých bunek v dospelosti a prínos PET/CT vysetrení pri hodnocení difuzní metabolické aktivity v plicním parenchymu.

The case report given here describes an unusual case of a 35-year-old otherwise healthy male diagnosed with aggressive form of Langerhans cell histiocytosis initially taking course under the form of lymphoma with expressed B symptoms (night sweats, fever and weight loss) and generalized peripheral lymphadenopathy. Also present were productive cough and perianal itching. The diagnosis was determined from lymph node and perianal skin biopsies. Furthermore, by a typical finding on HRCT (high-resolution computed tomography), pulmonary involvement was confirmed the gradual development of which we succeeded to document through a series of several HRCT and PET/CT scans from its initial florid phase characterized by disseminated nodularities up to the terminal phase with the decline of activity and development of cystic formations. After the collection of peripheral blood stem cells, the planned patient's therapy started which in all consisted of three monotherapy cycles with cladribine followed by three cycles of combined chemotherapy (cladribine + cyclophosphamide + methylprednisolone) and complemented with curative radiotherapy of the perianal area. This treatment put the disease into complete remission. However, in two months the initial B-symptoms occurred again, along with the pulmonary symptomatology, perianal pruritus and newly also hip bone pains. The suspected LCH relapse was proved histologically by lymph node biopsy and confirmed at a restaging PET/CT examination which also showed disease dissemination into the hip bones. Consequently, an aggressive form of the disease with early relapse had been the case, which was indicated for administering 4 cycles of CHOEP (cyclophosphamide + doxorubicin + vincristine + etoposide + prednisone) as salvage regimen completed in March 2010 with autologous peripheral blood stem cell transplantation after high-dose BEAM (carmustine + etoposide + cytarabine + melphalan) chemotherapy. Thus, the generalized involvement of nodes doesn't always need to be malignant lymphoma or metastatic dissemination of a tumour but also LCH may be the case. The presence of B symptoms may very likely stand for an aggressive form of the disease course. Histological evaluation of the proliferative characteristic (given by Ki-67 immunohistochemical proliferative index marker and also morphologically by the number of mitosis) may draw attention to an aggressive form of this disease. However, therapy with cladribine (2-chlorodeoxyadenosine) which proves beneficial in classic forms of LCH, in cases of highly aggressive forms of LCH doesn't need to have the same effect as in LCH with low proliferative activity, which conforms to the present experience in the treatment of indolent and aggressive lymphomas. In our study, the hybrid PET/CT imaging proved high sensitivity in evaluating the activity of the disease, including its early relapse. We are presenting here a new method for description and evaluation of diffuse increased activity of pulmonary parenchyma by means of PET/CT examination and for using this method within the framework of monitoring the curative response.

[Interdigitating dendritic cell sarcoma of lower extremities resistant to high dose chemotherapy BEAM with peripheral blood stem cell transplantation]. / Sarkom z interdigitujících dendritických bunek dolní koncetiny rezistentní k vysokodávkované chemoterapii BEAM s autologní transplantací kmenových krvetvorných bunek--popis prípadu a prehled literatury.

Interdigitating dendritic cell sarcoma is a rare neoplasm forming part of the group of malignancies derived from histocytic cell line. This nosological unit can be detected only by special immunohistochemical exams. A young man aged 25 found a tumorous swelling in the proximal part of his left crus. The pathological process affected proximal tibial epiphysis and adjacent soft tissues. The first FDG-PET examination performed in the process of determining the clinical stage of the disease showed a high activity in the site of primary tumour (SUV 7.71) and in the site of regional inguinal node (SUV 4.25). Histological examination of a diagnostic excision specimen of the tumour in the tibia and the extirpated enlarged regional nodes in the left groin led to the diagnosis of interdigitating dendritic cell sarcoma. The diagnosis was confirmed pathologically by another two centres in the Czech Republic and, due to the unusual nature of the diagnosis, also in Regensburg, Germany. Treatment started with chemotherapy, applied to patients with aggressive lymphomas in the framework of clinical studies, i.e. a combination of MegaCHOP. After 4 cycles, however, there was no visible response on the site of primary tumour. MegaCHOP therapy was therefore discontinued after the 4 cycles. Subsequently, we referred the patient for a high-dose chemotherapy with autologous bone marrow transplantation, similarly to aggressive lymphomas. The collection of blood producing stem cells from peripheral blood was successfully performed after ESHAP chemotherapy. A verificatoin FDG-PET examination was performed before high-dose chemotherapy. Increased activity was detected only in left proximal crus, with an SUV of 4.6. One month after ESHAP chemotherapy, BEAM high-dose chemotherapy with autologous transplantation of blood forming tissue was performed. High-dose chemotherapy was followed up by radiotherapy targeted on the primary tumour in the crus (70 Gy). The third verification FDG-PET examination was performed 3 months after radiotherapy. The examination showed a continuing higher activity in the region of the primary tumour (SUV 2.69) and a new centre of activity was detected in the left inguinal nodes region (SUV4.09). The activity corresponded to the presence of viable tumour tissue in the primary nidus and new metastases in inguinal nodes, without proofs of further proliferation at the time. Nodes of the left groin were removed. Histological examination showed affection of the node by the same type of tumour, i.e. a continuing activity of the disease despite chemotherapy. Due to suspected continuation of viable tumour in the crus judging by the intensity of accumulation of FDG-PET and the proof of a new affection of regional nodes, surgical treatment was preferred after the failure of chemotherapy. After the removal of inguinal nodes, left knee joint exarticulation was performed. This was followed by regional inguinal node region radiotherapy (56 Gy). The last fourth PET-CT examination carried out 4 months after the radiation therapy of the inguinal region showed massive dissemination into the region ofileac and paraaortic nodes (lymphadenopathy up to 6 cm in diameter) with an activity of 5.9 to 6.73 SUV units. Currently, we test the sensitiveness of the disease to 2-chlordeoxyadenosin and look for additional therapeutic options. To our knowledge, the above description is the first documented case of interdigitating dendritic cell sarcoma located in the tibia and crus soft tissue. We have not found any description of high-dose therapy supported by autologous transplantation of blood-forming tissue for this type of tumour in relevant literature. In this case, we record chemoresistance to high-dose chemotherapy and certain radiosensitivty of the tumour at the same time.

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.

[Invasive aspergillosis in hematooncological patients: advantages and disadvantages of various diagnostic methods, treatment options and financial costs of therapy]. / Invazivní aspergilové infekce u hematoonkologických nemocných: význam jednotlivých diagnostických metod, lécebných postupu a nástin financní nárocnosti lécby.

BACKGROUND: Invasive aspergillosis (IA) is a leading invasive fungal infection in hematooncological patients. The aim of this study was to analyse the incidence, diagnostic procedures and treatment of IA in hematooncological department in large hospital in the Czech Republic. PATIENTS AND METHODS: A retrospective analysis of medical and laboratory records from patients hospitalised in our department with proven/probable IA between January 2000 and December 2006 was performed. RESULTS: 52 cases of IA in 51 patients were identified (17.3% proven IA/82.7% probable IA). Number of IA cases notably increased during study period (1 case of IA in 2000 vs 21 cases of IA in 2006) and majority of them was of nosocomial origin (61.5%). Pulmonary aspergillosis was diagnosed in 46 cases (88.5%). Patients treated for acute leukemia or undergoing allogeneic stem cell transplantation represent the group at the highest risk of IA (in total 52% of cases). Fever and signs of pulmonary involvement were the most common clinical signs of infection (presented in 92.3% and 69.2 cases respectively). Conventional diagnostic methods including autopsy were able to diagnose only 15 cases of IA (28.8%). In all other cases (71.2%) the diagnosis was done by detection of galactomannan (GM) in serum. Introduction of GM monitoring enabled erlier initiation of antifungal treatment by 4 days. Initial therapy of IA led to the treatment response (partial and complete) in 18 (34.6%) of infections--the highest percentage of response has been seen in voriconazole monotherapy group (42%) and when combination of voriconazole and caspofungin has been used (83%). Salvage therapy was initiated due to the failure of initial treatment in 21 (40.3%) of cases. Patients were treated mostly with combination ofvoriconazole and caspofungin and/or monotherapy with voriconazole has been used with treatment response 55% and 50% respectively. Introduction of new antifungal drugs together with increased number of patients with IA led to the marked increase of total costs spent on treatment of IA per year--from 11,5 thousands CZK in 2000 to 6,2 millions CZK in 2006. CONCLUSIONS: IA is the most frequent cause of infection-related mortality in patients with haematological malignancies. Routine use of non-culture base methods in diagnosis of IA together with treatment using new, effective antifungals can improve prognosis of patients with this life threatening infection.

Ovarian tissue cryopreservation--new opportunity to preserve fertility in female cancer patients.

INTRODUCTION: Malignant disease and the therapy are major factors that may result in complete loss of fertility. There are several strategies for fertility preservation in fertile women faced with cancer. A modern and potentially effective method of reproductive function protection is ovarian tissue cryopreservation. MATERIALS AND METHODS: This paper summarizes the medical and scientific knowledge in this interesting multidisciplinary medical field. Furthermore, the authors' own experience with this novel and interesting method of ovarian tissue protection is presented. Ovarian tissue was obtained during laparoscopic surgery in five nuliparous women (aged 19-33) with a diagnosis of lymphoma before chemotherapy from 2004 to 2006. After laboratory preparation, tissue was frozen by a slow cooling technique and stored in liquid nitrogen. RESULTS: In total 75 women with malignant lymphoma before chemotherapy were referred to our center for consultation--68 chose ovarian inactivation by GnRH analogues during chemotherapy, two IVF cycles with embryo or oocyte cryopreservation and five ovarian tissue cryopreservation. In these five women one to two slices of ovarian cortex from both ovaries were recovered. Totally 20 cryotubes with three pieces of tissue in each were cryopreserved. In no case was metastasis of cancer cells found by histological evaluation. CONCLUSIONS: Cryopreservation of ovarian tissue represents an effective alternative or addition to the cryopreservation of embryos or oocytes for women at risk of premature ovarian failure due to chemotherapy. Reproductive function protection requires close cooperation between oncology departments and assisted reproduction centers.

[Ovarian tissue cryopreservation--an opportunity to preserve fertility in women with cancer]. / Kryokonzervace ovariální tkáne--sance na záchranu fertility zen s nádorovým onemocnením.

Chemoterapy is one of the basic modalities of oncological therapy and usually leads to permanent consequences. Infertility is one of the most common consequences resulting from irreversible gonadal damage. The potentially effective method of reproductive function protection in women undergoing chemotherapy is ovarian tissue cryopreservation. This paper summarizes the medical and scientific knowledge in this interesting multidisciplinary medical field an also presents authors own experience with this novel and interesting method of ovarian tissue protection.

Evaluation of acute and early cardiotoxicity in survivors of Hodgkin's disease treated with ABVD or BEACOPP regimens.

The study was conducted to compare the presence of cardiotoxicity after the treatment of Hodgkin's disease with the standard ABVD or BEACOPP protocol. We examined 29 patients treated by means of the ABVD regimen and 34 treated with the BEACOPP regimen. Using rest echocardiography we assessed the left ventricular function before and after the therapy. One year after the completion of therapy, a control examination was performed with a battery of tests; the rest and dynamic stress echocardiography and cardiopulmonary tests were carried out to assess cardiopulmonary performance. A similar significant deterioration of ejection fraction and diastolic function was apparent after the treatment in both sub-groups with a further progression at the one-year control. Only one patient from the BEACOPP sub-group showed a pathological drop of EF <50%. The most affected parameters of left ventricular function (LV) were Doppler indices. We found a significant relationship of the parameters of LV function compared with age, the cumulative dose of doxorubicin and the cumulative dose of radiotherapy. Multivariate analysis demonstrated that diastolic dysfunction correlated with advanced age and the cumulative dose of doxorubicin, and decreased cardiopulmonary performance with advanced age, radiotherapy, and female gender. Both parameters were significantly influenced by the presence of hypertension. The used regimens demonstrated similar subclinical cardiotoxicity, thus the most aggressive regimen, BEACOPP, is not accompanied by a higher rate of cardiac impairment. The clinical value of such subclinical cardiotoxicity will be estimated in a further prospective follow-up.

Echocardiographic evaluation of early and chronic cardiotoxicity in adult patients treated for Hodgkin's disease with ABVD regimen.

The prospective study was conducted to determine whether standard regimen ABVD used in the treatment of Hodgkin's disease is accompanied by the presence of early and chronic myocardial impairment. The study comprised 52 patients (30 male and 22 female) aged 34+/-15 years (range 18-71; median 30) with Hodgkin's disease and the control group with 40 healthy volunteers (21 male and 19 female) aged 40+/-8 years (range 20-70; median 38). The maximal administered cumulative dose (CD) of doxorubicin was 297+/-50 mg/m2 (range 150-450; median 300). Radiotherapy of the mediastinum was delivered to 27 (52%) patients with a mean dose 41+/-4 Gy (range 30-46; median 42). Echocardiography was performed at baseline and before each course of chemotherapy. The control examination was done at one month after the treatment and after one year. The stress echocardiography was performed at one-year control. Significant change of ejection fraction (EF) during the treatment was observed only in 10 (18%) patients (7 male/3 female) aged 29+/-13 years (range 18-56; median 22). The mean toxic CD of doxorubicin was 170+/-33 mg/m2 (range 100-200; median 175) and the mean time of the onset EF decline was 13.3+/-3 weeks (range 8-16; median 14). These changes were asymptomatic, and all patients completed the treatment successfully. Four patients (8%) demonstrated significant asymptomatic decline of EF after the chemotherapy. When compared the value of EF after one-year examination, a stable significant decline of EF in the sub-group with early toxicity was found. Despite a difference in the rest EF, the exercise increment of EF did not reveal any significant difference among tested groups and the contractile reserve of the left ventricle in patients was not impaired. The present data shows that the treatment of Hodgkin's disease with the standard ABVD regimen is accompanied with mild early and chronic asymptomatic changes of the left ventricular function. These changes were not reversible during one-year 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 Hodgkin's 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.