[Salvage Treatment and the Role of Transplantation in Lymphomas]. / Záchranná lécba a role transplantací u lymfomu.

Despite achieving promising treatment results in patients with lymphoma, there is still a significant proportion of patients who relapse or have refractory disease. Salvage therapy followed by high dose treatment with autologous stem- cell transplantation is the standard of care in many of them. The role allogeneic stem- cell transplantation, especially after reduced intensity conditioning, is under extensive investigation. This review article presents current knowledge and recommendation in the salvage treatment of relapsed/ refractory lymphomas.

[Treatment of patients with relapsed/refractory Hodgkin lymphoma]. / Lécba pacientu s relabovaným/refraktérním Hodgkinovým lymfomem.

BACKGROUNDS: This retrospective study evaluated treatment outcomes in patients undergoing autologous stem cell transplantation (ASCT) for relapsed/refractory Hodgkin lymphoma (HL). PATIENTS AND METHODS: Overall, 194 HL patients treated with ASCT between 2000 and 2009 were analyzed. Survival was calculated using Kaplan-Meier method and differences in survival between subgroups with log-rank test. RESULTS: Best responses observed after ASCT: 124 complete and 35 partial remissions, 2 patients with stable disease and 33 relapses/progressions. During a median follow-up of 44 months, seventy patients after ASCT progressed/relapsed. Thirty-seven patients received salvage chemotherapy only with or without radiotherapy, 25 underwent allogeneic stem cell transplantation (SCT), 4 the second ASCT and 4 refused treatment. 5-year overall survival after ASCT was 71% and progression-free survival 54%. Median survival of the 70 patients relapsing after ASCT was 16.9 months. Median survival in patients after allogeneic SCT was 31.8 months and 12.4 months in patients treated with other modalities (p = 0.21). Overall mortality was 26.3% (51/194 patients): 13.4% progressions/relapses of HL and 12.9% non-relapse mortality. CONCLUSION: Efficacy of ASCT was confirmed in 54% progression-free survivors. Median survival after ASCT failure is relatively short. There is a slightly longer overall survival after allogeneic SCT, although not statistically significant when compared to other approaches.

Retrospective analysis of the results of high-dose chemotherapy with the support of autologous blood stem cells in patients with multiple myeloma. The experience of a single centre.

Despite new medical products introduced in multiple myeloma therapy, autologous stem cell transplant (ASCT) remains a standard procedure in younger patients with symptomatic disease. We analyzed a group of 190 patients who underwent ASCT at our clinic for multiple myeloma as primary therapy in years 1995-2008. The total number of transplants performed in this group was 291. 110 patients underwent one ASCT, 59 patients had double transplant, out of which 51 patients underwent tandem transplant, 21 patients underwent triple ASCT, out of which 15 patients were transplanted front-line throughout a clinical trial and 6 patients underwent follow-up transplants due to disease progression. The assessment of the best therapeutic effect of ASCT showed the total rates of patients with complete remission--22%, very good partial remission (VGPR)--8%, partial remission--63%, stabilized disease--6% and progression--1%. The transplant related mortality (TRM) was 4.1%. With the median follow-up of surviving patients 2.6 years, the median progression-free survival (PFS) and overall survival (OS) were 21 and 54 months, respectively; the likelihood of a 7-year overall survival was 28%. Comparing tandem versus single transplants, there was a significant increase in the median PFS (25.8 versus 20.8 months, respectively); however, there was no difference in overall survivals. The IVE mobilization regimen was found to be more efficacious for PBPC collection than high-dosed cyclophosphamide.

Positron emission tomography at the end of first-line therapy and during follow-up in patients with Hodgkin lymphoma: a retrospective study.

BACKGROUND: Routine positron emission tomography (PET) in follow-up of Hodgkin lymphoma (HL) after treatment is still controversial. The aim of this retrospective study was to analyze the clinical impact of routine PET examination during the follow-up for relapse detection in PET-negative HL patients at the end of therapy. PATIENTS AND METHODS: PET scans were carried out in 113 HL patients at the end of therapy and during the follow-up either in regular intervals or in a suspected relapse. Median follow-up of the group was 34 months. RESULTS: Overall 327 PET scans were evaluated in 113 patients (median three PET scans per patient). At the end of therapy, 94 (83.2%) patients were PET negative and 19 (16.8%) PET positive. Regular follow-up PET scans in 67 of 94 PET-negative patients correctly identified tumor in 6 of 155 PET scans (3.9%). In 27 of 94 patients with clinically suspected relapse, 5 of 27 PET scans (18.5%) confirmed tumor. CONCLUSIONS: Our analysis showed that there is no need for regular follow-up with PET scans in PET-negative patients at the end of therapy: the ratio of true-positive PET scans during the follow-up is low (3.9%). Positive PET at the end of therapy and during follow-up should be evaluated with caution.

[Cefepime as an empiric treatment of febrile neutropenia in patients after high dose therapy and autologous stem cell transplantation]. / Cefepim v empirické terapii febrilní neutropenie u pacientu lécených vysokodávkovanou chemoterapií s autologní transplantací krvetvorných bunek.

BACKGROUND: Febrile neutropenia is one of the most frequent complications in intensively treated hematooncological patients and almost inevitably occurs after high dose therapy and autologous stem cell transplantation. Empiric broad-spectrum antibiotic treatment is indicated in the initial management. Fourth-generation cephalosporins are the option. This retrospective study was initiated to assess efficacy and safety of cefepime as an empiric therapy of febrile neutropenia following high dose therapy and autologous stem cell transplantation. METHODS AND RESULTS: 319 high dose therapy procedures with autologous stem cell transplantation in 287 patients mostly with hematological malignancies were performed at our department between January 2002 and December 2005. We present analysis of 169 out of 229 febrile episodes in 163 patients (median age 53) being treated with cefepime in the initial empiric treatment of febrile neutropenia. 12 episodes (7.1 %) were clinically documented (pneumonia 9, sinusitis 2, acute cholecystitis 1), 60 (35.5 %) were confirmed microbiologically (presented as bacteremia) and 97 (57.4 %) were fever of unknown origin. 50 isolates (83.4 %) out of 60 microbiologically documented infections were G-positive bacteria, 8 isolates (13.3 %) were G-negative bacteria and 2 (3.3 %) were mixed G-positive and G-negative cultures. According to the MASCC score 14 episodes were assessed as high risk. Effect of cefepime as a single agent was observed in 85 episodes (50.3 %) and in 22 (13.0 %) episodes treated with combination therapy due to susceptibility of isolated pathogen in blood culture. Combination therapy of two antibiotics (cefepime + aminoglycoside or glycopeptide) given for persistent fever was effective in 13 patients (7.7 %). Treatment failure was observed in 48 (28.4 %) episodes, we registered 10 death. CONCLUSIONS: Therapy with cefepime represents an appropriate choice for empiric antibiotic treatment of febrile neutropenia in hematooncological patients. Cefepime demonstrates clinical safety and efficacy and can be used in monotherapy or in combination with other drugs (overall response 72.2 %, as a single agent 50.3 %).

[High dose therapy with autologous stem cell transplantation in patients with Hodgkin's lymphoma: long-term follow-up in patients treated in one center]. / Vysokodávkovaná terapie s autologní transplantací krvetvorných bunek u nemocných s Hodgkinovým lymfomem: dlouhodobé sledování nemocných lécených v jednom centru.

BACKGROUND: Majority of patients with Hodgkin's Lymphoma (HL) can be cured by first line therapy. The high dose therapy (HDT) with autologous stem cell transplantation (ASCT) is the option which can be used in the situation when the conventional therapy failed. METHODS AND RESULTS. Beginning 1994 till 2005 84 pts with HL who did not respond the conventional chemotherapy underwent 105 HDT procedures with ASCT. The median age at the time of HDT was 30.5 years. The reason for salvage therapy followed by HDT with ASCT was the failure to achieve 1st complete remission-- CR (n 16) or the subsequent relapse or progression (n 68). The disease status at the time of HDT after conventional salvage chemotherapy was assessed as chemosensitive in 65 pts (77.4%) and chemoresistant in 19 pts (22.6%). The most frequent HDT regimen used was BEAM (82 HDT), 22 pts entered into the tandem HDT program. Bone marrow only was used as the source of progenitor cells in 4 ASCT, peripheral blood progenitor cells (PBPC) only were used in 85 ASCT and the combination of both in 16 ASCT. The disease status after the HDT with ASCT was assessed (77 pts were qualifiable) as CR in 39 pts (50.6%), PR in 31 (40.3%) and as stable disease or progression in 7 pts (9.1%). Treatment related mortality in HDT with PBPC was 3.9%. The median follow up is 5.3 years. The five year probability of event free survival (EFS) is 43.1% and overall survival 53.2%. The EFS and OS probability respectively for the chemosensitive patients was 48.6% and 62.9% respectively. The status at HDT and the results after it have prognostic significance. There were observed 39 deaths and 26 of them were caused by disease progression. Secondary tumor was observed in 5 pts and in all of them it caused the death. CONCLUSIONS: The HDT with ASCT allows the long-term survival without disease progression in about a half of the patients with reasonable toxicity.

[Relapse in Hodgkin's disease. Incidence of relapse in a group of 374 patients from 1 June 1968 to 31 March 1995]. / Relaps Hodgkinovy choroby. Incidence relapsu v souboru 374 nemocných v období od 1. 6. 1968 do 31. 3. 1995.

From a group of 366 patients with complete data complete remission was achieved by 290. Fifty-five patients relapsed, 39 men and 16 women, mostly with an initial finding of advanced disease (KS III + IV 64%), with affection of the mediastinum (73%) aged under 40 years. 42% of the relapses were detected within one year after termination of primary treatment and 33% during the subsequent 2 years, the longest interval before a relapse being 20 years. During primary treatment in 63% of the patients chemotherapy was reduced to 75-25% of the total dose of cytostatics with protraction of the interval between cycles in 58% and radiotherapy in another 34% of the patients. 76% of the patients with a first relapse achieved a second complete remission and 29 of them survive without signs of the disease, 12 died from generalized lymphoma. Sixteen patients developed repeated relapses (nine two relapses, four three relapses, another two four relapses and one patient five relapses). After treatment of the relapse a total of 22 patients died, incl. 19 who died from Hodgkin's disease, two from secondary carcinoma and one from myocardial infarction. The longest survival period after treatment of a relapse was 26 years.

[The significance of mediastinal involvement and other risk factors for survival in patients with Hodgkin's disease]. / Význam postizení mediastina a dalsích rizikových faktoru pro prezití nemocných s Hodgkinovou chorobou.

The impact of prognostic factors for survival was analyzed in a group of 337 patients with Hodgkin's disease. The analysis of survival of patients comprised a total of 13 indicators: histological types LP, NS, MC, LD, clinical stages I, II, III, IV, E lesions, symptomatology A, B, size of the mediastinal tumour (index), age at onset of disease and sex. Cumulative survival of 5, 10, and 20 years in the whole group is 83%, 80% and 72% resp. A first complete remission was achieved by 284 patients, cumulative survival without the disease is 79% after 5 and 73% after 10 years since completion of primary treatment. A significantly adverse effect on the prognosis of survival is exerted by symptomatology B, a large mediastinal tumour, advanced age, clinical stage IV and III. Most important are the first two factors mentioned. An adverse prognostic factor for survival without disease is male sex. The therapeutic protocol was repeatedly modified in the course of 25 years with regard to prognostic patient groups.

[Pulmonary complications and their prevention in the treatment of Hodgkin's disease]. / Plicní komplikace lécby u Hodgkinovy choroby a jejich prevence.

Pulmonary ventilation was monitored in a group of 102 patients with Hodgkin's disease. In the initial finding a tendency of a restrictive disorder is apparent (43% of the patients) with the increasing size of the mediastinal tumour (79% mediastinal patients with a bulky finding in 40%), without statistical significance. After treatment a restrictive disorder was recorded in 35% of the patients with a normal initial finding and conversely normalization of results occurred in 12% patients with a pathological result of the spirometric examination. After a one-year interval the finding deteriorated in 12 % of the patients without post-treatment disorders of pulmonary ventilation and in 15% the assessed disorder receded. Statistical analysis did not reveal a significant relationship between the results of spirometry and bleomycin treatment. 77 patients were examined after an interval of 2, 3, 4 and more years following termination of primary treatment without a significant correlation of the development of the a restrictive disorder and bleomycin administration. Pulmonary ventilation after treatment was examined in a total of 228 patients with the finding of restrictive changes in 94 (41%). Pulmonary fibrosis was diagnosed in 21 patients (9%) with a rising incidence two years after terminated treatment.

[Children of parents treated for Hodgkin's disease using irradiation and chemotherapy]. / Deti rodicu lécených zárením a chemoterapií pro morbus Hodgkin.

The authors describe data on the course of pregnancy, delivery and subsequent development of 20 children born to parents treated for Hodgkin's disease. Thirteen women in the clinical stage II and III were delivered of 16 infants (10 daughters and 6 sons) and three men (II A and III A) had four daughters. The parents were in one case treated by irradiation only, twice by chemotherapy only and thirteen times by a combination of irradiation and chemotherapy (COPP/ABVD). The gestation period, parameters of the infants at delivery and the subsequent physical and mental development are normal. In one instance (a girl, now ten and a half years old) the child was born with malformations of the extremities; according to the geneticist this is not related to the previous treatment of the mother. The second child (a son) of this mother is normal. The authors are of the opinion and apply it in the therapeutic protocol in patients of fertile age and do not irradiate nodes in the pelvic region. In treated patients they allow pregnancy only after three or preferably five years following terminated treatment. Survival of patients in the whole group (269 subjects) regardless of age and clinical stage is 75%. The authors are processing a data base of Hodgkin patients since 1968.