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Abstract Background The current situation in the treatment of chronic myeloid leukaemia (CML) presents a new challenge for attempts to measure the therapeutic results, as the CML patients can experience multiple leukaemia-free periods during the course of their treatment. Traditional measures of treatment efficacy such as leukaemia-free survival and cumulative incidence are unable to cope with multiple events in time, e.g. disease remissions or progressions, and as such are inappropriate for the efficacy assessment of the recent CML treatment. Methods Standard nonparametric statistical methods are used for estimating two principal characteristics of the current CML treatment: the probability of being alive and leukaemia-free in time after CML therapy initiation, denoted as the current cumulative incidence of leukaemia-free patients; and the probability that a patient is alive and in any leukaemia-free period in time after achieving the first leukaemia-free period on the CML treatment, denoted as the current leukaemia-free survival. The validity of the proposed methods is further documented in the data of the Czech CML patients consecutively recorded between July 2003 and July 2009 as well as in simulated data. Results The results have shown a difference between the estimates of the current cumulative incidence function and the common cumulative incidence of leukaemia-free patients, as well as between the estimates of the current leukaemia-free survival and the common leukaemia-free survival. Regarding the currently available follow-up period, both differences have reached the maximum (12.8% and 20.8%, respectively) at 3 years after the start of follow-up, i.e. after the CML therapy initiation in the former case and after the first achievement of the disease remission in the latter. Conclusions Two quantities for the evaluation of the efficacy of current CML therapy that may be estimated with standard nonparametric methods have been proposed in this paper. Both quantities reliably illustrate a patient's disease status in time because they account for the proportion of patients in the second and subsequent disease remissions. Moreover, the model is also applicable in the future, regardless of what the progress in the CML treatment will be and how many treatment options will be available, respectively.

Abstract Background MicroRNAs are important regulators of transcription in hematopoiesis. Their expression deregulations were described in association with pathogenesis of some hematological malignancies. This study provides integrated microRNA expression profiling at different phases of chronic myeloid leukemia (CML) with the aim to identify microRNAs associated with CML pathogenesis. The functions of in silico filtered targets are in this report annotated and discussed in relation to CML pathogenesis. Results Using microarrays we identified differential expression profiles of 49 miRNAs in CML patients at diagnosis, in hematological relapse, therapy failure, blast crisis and major molecular response. The expression deregulation of miR-150, miR-20a, miR-17, miR-19a, miR-103, miR-144, miR-155, miR-181a, miR-221 and miR-222 in CML was confirmed by real-time quantitative PCR. In silico analyses identified targeted genes of these miRNAs encoding proteins that are involved in cell cycle and growth regulation as well as several key signaling pathways such as of mitogen activated kinase-like protein (MAPK), epidermal growth factor receptor (EGFR, ERBB), transforming growth factor beta (TGFB1) and tumor protein p53 that are all related to CML. Decreased levels of miR-150 were detected in patients at diagnosis, in blast crisis and 67% of hematological relapses and showed significant negative correlation with miR-150 proved target MYB and with BCR-ABL transcript level. Conclusions This study uncovers microRNAs that are potentially involved in CML and the annotated functions of in silico filtered targets of selected miRNAs outline mechanisms whereby microRNAs may be involved in CML pathogenesis.

Diffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody--drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells. METHODS We conducted a double-blind, placebo-controlled, international phase 3 trial to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP, plus two cycles ofrituxinlab alone. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival and safety. RESULTS Overall, 879 patients underwent randomization: 440 were assigned to the pola-R-CHP group and 439 to the K-CHOP group. After a median follow-up of 28.2 months, the percentage of patients surviving without progression was significantly higher in the pola-R-CHP group than in the R-CHOP group (76.7% [95% confidence interval (CI), 72.7 to 80.8] vs. 70.290 [95% CI, 65.8 to 74.6] at 2 years; stratified hazard ratio for progression, relapse, or death, 0.73 by Cox regression; 95% CI, 0.57 to 0.95; P=0.02). Overall survival at 2 years did not differ significantly between the groups (88.7% [95% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6% [95% CI, 85.6 to 91.6] in the R-CHOP group; hazard ratio for death, 0.94,95% CI, 0.65 to 1.37; P=0.75). The safety profile was similar in the two groups. CONCLUSIONS Among patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP. (Funded by F. Hoffmann-La Roche/Genentech; POLARIX ClinicalTrials.gov number, NCT03274492.) [ABSTRACT FROM AUTHOR]

This study's focus is the association of end-of-therapy (EOT) PET results with progression-free (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma receiving first-line chemoimmunotherapy. We develop a Bayesian hierarchical model for predicting PFS and OS from EOT PET-complete response (PET-CR) using a literature-based meta-analysis of 20 treatment arms and a substudy of 4 treatment arms in 3 clinical trials for which we have patient-level data. The PET-CR rate in our substudy was 72%. The modeled estimates for hazard ratio (PET-CR/non-PET-CR) were 0.13 for PFS (95% CI 0.10, 0.16) and 0.10 for OS (CI 0.07, 0.12). Hazard ratios varied little by patient subtype and were confirmed by the overall meta-analysis. We link these findings to designing future clinical trials and show how our model can be used in adapting the sample size of a trial to accumulating results regarding treatment benefits on PET-CR and a survival endpoint.

Introduction: The prognostic value of B-cell lymphoma 2 (BCL2) expression in de novo diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy is of interest to define a target patient population for clinical development of BCL2 inhibitors. We aimed to develop a reproducible immunohistochemistry algorithm and assay to determine BCL2 protein expression and assess the prognostic value of BCL2 in newly diagnosed DLBCL cohorts., Patients and Methods: The prospectively defined algorithm incorporated BCL2 staining intensity and percentage of BCL2-positive cells. Functionally relevant cutoffs were based on the sensitivity of lymphoma cell lines to venetoclax. This assay was highly reproducible across laboratories. The prognostic impact of BCL2 expression was assessed in DLBCL patients from the phase 3 MAIN (n = 230) and GOYA (n = 366) trials, and a population-based registry (n = 310)., Results: Approximately 50% of tumors were BCL2 positive, with a higher frequency in high International Prognostic Index (IPI) and activated B-cell-like DLBCL subgroups. BCL2 expression was associated with poorer progression-free survival in the MAIN study (hazard ratio [HR], 1.66; 95% confidence interval [CI], 0.81-3.40; multivariate Cox regression adjusted for IPI and cell of origin). This trend was confirmed in the GOYA and registry cohorts in adjusted multivariate analyses (GOYA: HR, 1.72; 95% CI, 1.05-2.82; registry: HR, 1.89; 95% CI, 1.29-2.78). Patients with BCL2 immunohistochemistry-positive and IPI-high disease had the poorest prognosis: 3-year progression-free survival rates were 51% (GOYA) and 37% (registry)., Conclusion: Findings support use of our BCL2 immunohistochemistry scoring system and assay to select patients with BCL2-positive tumors for future studies., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

This phase II, single-arm, multicenter study examined the efficacy and safety of coltuximab ravtansine (an anti-CD19 antibody drug conjugate) in 61 patients with histologically documented ( de novo or transformed) relapsed or refractory diffuse large B-cell lymphoma who had previously received rituximab-containing immuno-chemotherapy. Patients had received a median of 2.0 (range 0-9) prior treatment regimens for diffuse large B-cell lymphoma and almost half (45.9%) had bulky disease (≥1 lesion >5 cm) at trial entry. Patients received coltuximab ravtansine (55 mg/m 2 ) in 4 weekly and 4 biweekly administrations until disease progression or unacceptable toxicity. Forty-one patients were eligible for inclusion in the per protocol population. Overall response rate (International Working Group criteria) in the per protocol population, the primary end point, was 18/41 [43.9%; 90% confidence interval (CI:) 30.6-57.9%]. Median duration of response, progression-free survival, and overall survival (all treated patients) were 4.7 (range 0.0-8.8) months, 4.4 (90%CI: 3.02-5.78) months, and 9.2 (90%CI: 6.57-12.09) months, respectively. Common non-hematologic adverse events included asthenia/fatigue (30%), nausea (23%), and diarrhea (20%). Grade 3-4 adverse events were reported in 23 patients (38%), the most frequent being hepatotoxicity (3%) and abdominal pain (3%). Eye disorders occurred in 15 patients (25%); all were grade 1-2 and none required a dose modification. Coltuximab ravtansine monotherapy was well tolerated and resulted in moderate clinical responses in pre-treated patients with relapsed/refractory diffuse large B-cell lymphoma. (Registered at: clinicaltrials.gov identifier: 01472887) ., (Copyright© 2018 Ferrata Storti Foundation.)

In the mantle cell lymphoma (MCL)-002 study, lenalidomide demonstrated significantly improved median progression-free survival (PFS) compared with investigator's choice (IC) in patients with relapsed/refractory MCL. Here we present the long-term follow-up data and results of preplanned subgroup exploratory analyses from MCL-002 to evaluate the potential impact of demographic factors, baseline clinical characteristics and prior therapies on PFS. In MCL-002, patients with relapsed/refractory MCL were randomized 2:1 to receive lenalidomide (25 mg/day orally on days 1-21; 28-day cycles) or single-agent IC therapy (rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine). The intent-to-treat population comprised 254 patients (lenalidomide, n = 170; IC, n = 84). Subgroup analyses of PFS favoured lenalidomide over IC across most characteristics, including risk factors, such as high MCL International Prognostic Index score, age ≥65 years, high lactate dehydrogenase (LDH), stage III/IV disease, high tumour burden, and refractoriness to last prior therapy. By multivariate Cox regression analysis, factors associated with significantly longer PFS (other than lenalidomide treatment) included normal LDH levels (P < 0·001), nonbulky disease (P = 0·045), <3 prior antilymphoma treatments (P = 0·005), and ≥6 months since last prior treatment (P = 0·032). Overall, lenalidomide improved PFS versus single-agent IC therapy in patients with relapsed/refractory MCL, irrespective of many demographic factors, disease characteristics and prior treatment history., (© 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.)

Vascular endothelial growth factor is involved in lymphoma growth, suggesting a potential role for anti-vascular endothelial growth factor therapies in hematologic malignancies. In this phase III study, patients with CD20-positive diffuse large B-cell lymphoma were randomized to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus either placebo (R-CHOP) or bevacizumab (RA-CHOP). Treatment was administered every 21 (8 cycles) or 14 days (6 cycles plus 2 rituximab cycles) as per institutional practice. An early analysis of risk/benefit by the Data and Safety Monitoring Board showed that RA-CHOP increased cardiotoxicity without prolonging progression-free survival compared with R-CHOP, and the trial was stopped early. The study protocol was amended to allow for 12 additional months of follow up to evaluate safety. With 787 patients enrolled, median follow up was 23.7 and 23.6 months for R-CHOP and RA-CHOP, respectively. Median progression-free survival for R-CHOP and RA CHOP was 42.9 and 40.2 months, respectively (hazard ratio=1.09; P=0.49). The proportion of deaths was identical for R-CHOP (83 of 387, 21%) and RA-CHOP (82 of 390, 21%). Relative to R-CHOP, RA-CHOP had a higher rate of left ventricular ejection fraction perturbation (18% vs. 8%; odds ratio=2.51; 95% confidence interval (CI): 1.60-3.93) and congestive heart failure (16% vs. 7%; odds ratio=2.79; 95%CI: 1.72-4.54). Bevacizumab added to R-CHOP increased cardiac events, without increasing efficacy, arguing against further evaluation of RA-CHOP in patients with diffuse large B-cell lymphoma. The MAIN study is registered at clinicaltrials.gov identifier:00486759., (Copyright© Ferrata Storti Foundation.)

Objective: The aim of the study is to show the possible variations of early symptoms of haematological malignity during pregnancy and to summarize data about treatment modalities and possible management of gravidity in case of the disease., Design: Case report., Setting: Department of Obstetrics and gynaecology, Charles University, 2nd Medical Faculty; 1st internal clinic - department of hematology, Charles University, 1st Medical Faculty, Prague., Methods: Pubmed database was searched between years 1989 and 2009. The data we used focused on non- Hodgkin's lymphomas diagnosed during pregnancy, especially on Burkitt lymphoma. The treatment modalities, neonate outcomes and prognosis of the mothers were emphasised., Conclusion: The diagnostics of haematological malignities in pregnancy is difficult. The most frequent symptoms are subfebris, fever of unknown etiology, lymphadenopathy, night sweats, infirmity and the weight lost. According to the literature the Burkitt lymphoma is potencialy currable disease during pregnancy. The close cooperation of the gynecologists and hematooncologists and the individualization of treatment based on the stage of pregnancy, localization of the tumorous mass and the agresivity of disease is needed.

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.

Transplantations of the autologous hematopoietic cell have been performed in the Czech Republic since 1993. Their total number has increased during the past ten years from 43 to more than three hundred procedures annually. Presented article describes, how the indications for autologous transplants have gradually changed according to the accumulating scientific evidence and it also gives examples of Czech researchers contributing to the advances in this field. Currently, autologous transplants belong to the standard treatment of a number of hemato-oncological diseases and further studies, both national and international, are being performed in Czech Republic. Their aim is to improve this role of the treatment modality in the global care for patients with these diagnoses.

Background: Retrospective study about results of treatment of patients (pts) with primary (AL) and secondary (AA) amyloidosis is given. 31 pts with systemic forms of amyloidosis have been treated and followed-up in our department since 1993., Methods and Results: 6 men and 11 women were in the AL group with the mean age of 59 years. Multiple myeloma was diagnosed in 9 pts, monoclonal gammapathy of undetermined significance (MGUS) was found in 8 pts. The kidneys were affected in all pts, heart in 59% of pts, liver, joints and skin in 26% of pts and polyneuropathy was detected only in 1 pt. Progression of renal insufficiency with decrease of glomerular filtration rate (GFR) was detected in the AL group at the end of follow-up period compared with the initial level (p < 0.05) despite the intensive treatment. The difference did not reach statistical significance in other investigated parameters. Median of survival was 13 months from the assessment of diagnosis. Partial remission of amyloidosis was achieved in 9 pts, stable disease was in 5 pts and in 3 pts the disease progressed. 4 men and 10 women were in the AA group with mean age of 58 years. Underlying disease was rheumatoid arthritis in 7 pts, ankylosing spondylitis in 2 pts, juvenile chronic arthritis in 1 pt, Crohn's disease in 2 pts, eosinophilic fasciitis in 1 pt and chronic abscesses in NK cell deficiency in 1 pt. The kidneys were affected in all pts, bowels and heart in 36% of pts. GFR (p < 0.05) and plasma creatinine (p < 0.01) significantly decreased at the end of follow-up period compared with initial levels. Median of survival was 30 months. Partial remission was achieved in 2 pts, stable disease was in 3 pts and progression was detected in 9 pts despite the use of various treatment regimens., Conclusions: Both forms of systemic amyloidosis represent severe disease with limited response to treatment. The use of new drugs is promising and could lead to better response to treatment.

Background: PCR techniques detecting interchromosomal translocation and clonal immunoglobulin gene rearrangement (IgH) as disease markers in non-Hodgkin's lymphomas (NHL) has been utilised past ten years. However, qualitative PCR detection of persisted minimal residual disease cannot provide clinically useful prognostic information and presently, quantitative approaches are required to predict patient outcome and assess response to the treatment. In some cases, "end-point" quantifying techniques, such as comparative PCR, are applicable and the relative estimation of differences in target quantity may serve in disease monitoring rather than absolute number of target copies., Methods and Results: Our method of comparative PCR employs co-amplification of sequences of interest (clonal CDR3, bcl2/Jh) and the segment of Hras 1 gene(ras) as an internal standard. Serial dilutions of stored diagnostic DNAs from blood and bone marrow are examined in the same PCR and, after gel densitometry, the amount of initial target is assessed by comparing exponential products of co-amplification. The comparative PCR assay was utilized in monitoring of NHL patients cured either with conventional therapy, or with high-dose regimens and transplantation with stem cells, or with chimaeric anti-CD20 monoclonal antibody (Rituximab). Results from 50 monitored intervals obtained during several months up to several years were supplemented with clinical statements retrospectively. Some of patients became PCR-negative, reappearance of PCR-positivity was observed as well. The decrease or increase of disease marker corresponded to clinical observations. Results obtained from bone marrow were in agreement with those obtained from blood., Conclusions: End-point quantifying PCR comparative assay may provide an information on the increased risk of relapse and impact of the therapy. The predictive value of these methods depends on the frequency of sample taking and on the sensitivity of the method, which should be monitored in negative cases.

Background: Positron emission tomography (PET) is a modern functional imaging method, recently introduced to clinical oncology. The aim of our study was the evaluation of prognostic value of PET performed in malignant lymphoma patients after two cycles of chemotherapy., Methods and Results: From 9/99 to 11/00 PET was performed in 37 patients with malignant lymphoma (9x m. Hodgkin, 21x HG + IG-NHL, 7x LG-NHL; 26x new diagnosis, 11x relaps of disease). Freedom from progression interval (FFP) and overall survival (OS) were evaluated. Attenuation corrected PET imaging was done by dedicated ECAT EXACT PET scanner from base of the skull to the upper thighs 1 hour after intravenous administration of 18-FDG (7.6 +/- 1.3 MBq/kg). Statistical analysis was done using Kaplan-Meier method. Significance of differences between groups was determined by log-rank test on the level of 5%. After the induction therapy, 30 patients were in complete remission, 3 patients in partial remission and in 4 cases progression of disease were observed. Progression of disease was seen in 4 patients. Median follow up of living patients was 7 months (1-13 months) from the end of therapy. Progression, resp. relapse of disease occurred in 13 patients during this period, two patients died. PET performed after the second course of therapy was positive in 18 patients and negative in 19 patients. Two progressions, resp. relapses of disease were documented in PET-negative group and 11 in PET-positive group. FFP was significantly different in PET positive and PET negative groups (p < 0.05). The negative and positive predictive values of PET for malignant lymphoma relapse or progression were estimated 89%, 63% respectively., Conclusion: Regardless the short follow-up period, our preliminary results reflect very good prognostic value of PET performed after the second course of chemotherapy in malignant lymphoma patients.

Cyclophosphamide (4 g/m2) and paclitaxel (Taxol) (175, 200 or 250 mg/m2) therapy with subsequent administration of G-CSF (10 micrograms/kg) has been used as intensification and as mobilization therapy for patients with breast cancer. This regimen was used in 19 patients, as part of adjuvant therapy in 14 and as part of therapy of metastatic disease in five. Median number of collected CD34+ cells was 17.5 x 10(6)/kg (2.9-48.1). All patients except one (94.7%) reached minimal required number of CD34+ cells (> or = 3 x 10(6)/kg). Median number of leukapheresis was two. The required number of cells (> or = 3 x 10(6)/kg) was collected in one leukapheresis in 17 out of 19 patients (89.5%) and more than five and 10 x 10(6)/kg CD34+ cells respectively were collected in 14 (73.7%) and 11 (57.9%) patients respectively. No factor significantly influencing the amount of collected cells (except the trend in favour of later year of therapy and large-volume leukapheresis) was identified. Leukopenia gr. 4 was observed in 88.9% of treated patients and febrile neutropenia developed in 46.2% patients. Although the antitumour activity of this chemotherapy was not possible to assess it seems that this intensification could be successfully used as a therapy and as very potent mobilization regimen.

Remarkable progress has been done during the last three decades in the therapy of hematological malignancies. It is now possible to cure significant number of patients by chemotherapy, radiotherapy, and stem cell transplantation. However, there is still a large group of patients and situations where our approaches are failing. It is evident that in some circumstance chemotherapy and radiotherapy get close to their limits. A short insight into the group of novel therapeutic methods is given in this review. Such promising methods of treatment include the new chemotherapeutic drugs, new molecules that specifically act on the level molecular mechanisms (STI 571, ATRA, arsenic trioxide, etc.), immunotherapy (monoclonal antibodies, vaccination strategy, exploration of dendritic cells etc.), gene therapy and innovations in stem cell transplantation (graft versus leukemia/lymphoma effect). The future treatment will include combination of standard or intensified chemo/radiotherapy and the new methods, which allow better control of the disease.

Positron emission tomography is a modern functional imaging method recently available also in the Czech Republic. The authors try to present indications of this method in the form of case-histories of patients with malignant lymphomas.

Background: A possible cause of relapses in patients with malignant lymphomas after autologous transplantation of haematopoietic cells is among others the absence of an immune reaction. The objective of the present study was to assess the effect of long-term interferon alpha administration after autologous transplantation in malignant lymphomas., Methods and Results: A total of 16 patients were followed up (9 men and 6 women, mean age 44 years) 14 with non-Hodgkin's lymphoma and two with Hodgkin's disease where after high-dose transplantation with autologous transplantation of haematopoietic cells immunotherapy was started by administration of IFN alpha 3 MU three time per week. The treatment was well tolerated, only in two patients (12.5%) the doses had to be reduced or temporarily discontinued. The results were compared with a control group (16 subjects, 12 men, 4 women, mean age 43 years and similar other characteristics as the followed up group) who were not given IFN alpha after transplantation. The controls were paired with regard to the condition after transplantation, grade of pretreatment, diagnosis and age. In the group treated with IFN alpha five relapses developed and two deaths occurred, in the control group four relapses and three deaths. The probability of survival without signs of progression (PFS) and total survival (OS) within 18 months is in the treated group 67.4% and 88.9%, in the control group 86.5% and 93.8%. The results are not statistically significant., Conclusions: The authors confirmed in their study the feasibility of long-term administration of IFN alpha after transplantation. On a preliminary basis it may be stated that the results did not differ in the treated and not treated patients, nevertheless the impact of this type of immunotherapy or its modification will have to be evaluated in a randomized study.

Background: Transplantations of haematopoietic progenitor cells from peripheral blood (PBPC) are able to ensure haematopoietic and immunological reconstitution as well as stable long term engraftment. Autologous PBPC are administered after previous myeloablative chemotherapy to patients with haematological and non-haematological malignancies. The objective of the submitted study was to follow-up the results of autologous separations of PBPC in patients with a good effect of mobilisation therapy. The authors evaluated in PBPC concentrates the content of cell parameters needed for transplantation. In the subsequent part of the trial they mention the times of engraftment after autologous transplantation., Methods and Results: The authors evaluated parameters of 26 separations of PBPC in 11 haematooncological patients with a good effect of mobilisation therapy and with concentration of CD 34+ cells higher than 20 x 10(3)/ml of peripheral blood. The separations of PBPC were implemented on the Cobe Spectra and Baxter CS 3000 Plus equipment under a standard regime with processing of 12 l blood, i.e. 2.7 total blood volumes of the patients. In the mentioned group of patients already from one separation an adequate amount of CD 34+ cells for their transplantation was obtained. Transplantation doses were prepared on average from two separations and amounted as regards MNC/kg, CD 34+ cells/kg and CFU-GM/kg to 4.3 x 10(8), 17.1 x 10(6) and 2.5 x 10(4). The assembled parameters correspond to, or in some parameters exceed, recommended amounts for their transplantation., Conclusions: In well mobilised patients under the regime of standard separations adequate amounts of progenitor cells for their autologous transplantation were obtained. Transplantation doses were prepared from two collections. Investigation of pre-separation concentration of CD 34+ cells in the peripheral blood is a reliable indicator for starting PBPC separation. Early post-transplantation results indicate the time of engraftment 10 days on average and minor need of substitution therapy with blood products.

Several cytokines stimulating hematopoiesis, mainly lineage restricted, are already widely used in supportive care to correct myelosuppression or anaemia (GM-CSF, G-CSF, EPO). The new growth factor are tested in preclinical or clinical studies to abrogate other anti-cancer therapy side-effects (thrombocytopenia, mucositis etc.). IL-3 has been shown to have only limited effect on neutrophils and platelets production respectively. IL-6 and IL-11 have been tested to improve thrombocytopenia and mucositis (IL-11). Thrombopoetin (TPO, c-mpl) is tested in clinical trials and shows very strong effect on platelet counts. Stem cell factor (SCF) has shown to improve progenitor cell mobilisation, particularly in combination with other cytokines. The new promising factor, FLT-3 ligand, combines effect on hematopoiesis with effect on dendritic cells generation. The new group of synthetic cytokines (daniplestim, myelopoetin, promegapoetin and progenipoetin) is now tested in preclinical and clinical studies. Mucositis could be influenced by new keratinocyte growth factor (KGF), which is now in phase I trials.

A 20 year-old black male presented with a generalized lymphadenopathy, skin papules with maximum involvement of the head and trunk region, and elevated temperature. Ultrasound, CT and bone scans revealed infiltration of the kidneys and bones. Surgical specimens of the cervical lymph nodes showed massive infiltration of sinuses by histiocytes with engulfed lymphocytes and granulocytes in their cytoplasm. A similar finding was found in the excised dermis and nasopharyngeal mucosa. Immunohistochemical investigations showed a strong positive reaction of sinusoidal macrophages with anti S100 protein, anti alpha-1 antitrypsin and alpha-1 antichymotrypsin antibodies, negative CD1a. The engulfed granulocytes were positive with lysozyme and MAC387 antibodies; lymphocytes reacted with antilymphocytic antibodies L26, HLADR, UCHL-1 and OPD4 only rarely, possibly due to alterations of their cell membranes in the cytoplasmic environment of histiocytes. Occasional plasma cells were also entrapped in the macrophages. The best results were obtained with CD3 antibody which showed focal predominance of phagocytosed T cells. These findings confirm a nonselective nature of the emperipolesis. In situ hybridization with probes EBER and BHLF against Epstein-Barr virus sequences was negative. The pacient was treated by multidrug chemotherapy with a moderate regression of the infiltrates. The symptoms of the disease persisted for 10 months from the treatment start but further course of the disease is uncertain. The patients is lost to follow up.

The cases of first-degree relatives from five families with hematological malignancies are described in this study. The occurrence of non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphoblastic leukemia (B-CLL) in the first family, NHL and chronic myeloid leukemia (CML) in the second one, two cases of Hodgkin's disease (HD) in the third and the fifth one's NHL and acute myelomonocytic leukemia (AMML) in the fourth one observed. Several factors which are considered to be involved in etiopathogenesis of hematological malignancies (virus infection, immune defects, HL-A antigens, cytogenic features) were discussed. Our study confirm other previous findings, that the familial susceptibility results from a combination of genetic and environmental influences.

The authors present an account of haematopoietic growth factors which include the stem cell factor (SCF), factors stimulating granulocytomacrophage colonies (GM-CSF), granulocyte (G-CSF), monocytomacrophage (M-CSF) factors, erythropoietin (EPO) and also interleukin (IL) 1 to 11. Their main action is described as well as the site of action in haematopoiesis. In many of them participation in the pathogenesis of some diseases, incl. malignant ones, is anticipated. The preparation of growth factors in a recombinant-form and knowledge of their effect made it possible to use them in clinical practice. The authors mention possible indications, although in many their administration still has the character of clinical studies.