Comparison of autologous hematopoietic cell transplantation performed in tandem and in disease relapse in multiple myeloma patients.

Multiple myeloma is a malignant hemato-oncological malignancy that affects up to 600 people in the Czech Republic every year. Treatment options are under constant improvement and the autologous hematopoietic cell transplantation (Tx) remains a part of treatment protocols. Despite modern drug administration, the autologous Tx keeps its irreplaceable position and when ensuring two autologous Tx, the studies confirm a survival time more than twice as long as in non-transplant patients. However, there are no standardized procedures specifying the period in between the transplantations in more detail. Within our group, we compared the total of 66 patients who were administered a double transplant. One group underwent both planned tandem autologous Tx within a median of six months and mostly achieved just partial remission (PR) and less after the first transplant and out of disease progression. The other group only underwent the second Tx within a median of up to 14 months during a progression period or disease relapse. Both groups were comparable as far as basic parameters are concerned (age, type of induction therapy and cytogenetic risk). A significantly better treatment free survival (TFX) and overall survival (OS) were observed in the group where tandem Tx was administered. TFS was 18 months and median OS was not reached for the group of patients who received tandem Tx, while TFS was 10 months (p=0.04) and median OS was 57 months (p=0.005) for those who received delayed second Tx. In the group of patients who received second Tx during relapse, we observed that TFS and OS were shorter in those with a higher paraprotein level, thus suggesting the potential role of paraprotein level as a prognostic marker. The TFS in the subgroup with a high initial level was 4 months vs. 11 months (p=0.0016) and OS 44 months vs. 65 months (p=0.03).

[Radiotherapy Indications in Patients with Hematological Malignancies During the Five Years Course of Modernized Center of Oncology and Radiotherapy Clinic in Pilsen]. / Indikace radioterapie u pacientu s hematologickými malignitami v prubehu peti let provozu modernizovaného centra Onkologické a radioterapeutické kliniky v Plzni.

Submitted: 27. 2. 2016.

[Spontaneous remission of acute myeloid leukemia - a single center case reports]. / Spontánní remise akutní myeloidní leukemie - klinické prípady jednoho centra.

BACKGROUND: Acute myeloid leukemia is a malignant disease characterized by clonal expansion of immature hematopoietic cells - myeloblasts - in the bone marrow. Intensive chemotherapy treatment in elderly patients (over 60) has disappointing results. In these patients, conservative treatment, including compensation of deficiency of red blood cells and platelets by transfusions and treatment of infectious complications is recommended. Also, relatively new treatment with hypometyl agents (azacytidine, decitabine) could be used. DESIGN: The idea of this article is to present a spontaneous remission phenomenon, which has not been published in Czech literature yet. In this article, we present 2 case studies of our patients who were diagnosed with acute myeloid leukemia, were not treated with chemotherapy and spontaneously reached remission of acute myeloid leukemia. CONCLUSION: The mechanisms of the spontaneous remission remain unclear, but we assume positive effect of a severe systemic infection or previous applications of blood transfusions. Antibodies in blood transfusions and a strong immune response to sepsis may have contributed to spontaneous remission.

[Angioimmunoblastic T-cell lymphoma as a very poor-prognosis malignancy--a single centre experience]. / Angioimunoblastický T-lymfom (AITL) jako velmi nepríznivá malignita - zkusenost centra.

BACKGROUND: Angioimmunoblastic T-lymphoma (AITL) is a poor prognosis malignancy. Because of relatively rare incidence and lack of publications in Czech, we decided to share our experience. PATIENTS AND METHODS: Retrospective analysis of newly diagnosed AITL patients treated at our institution between 1/2000-12/2010. RESULTS: Twelve patients with median age of 64 (43-82) years were analysed. Two patients over 80 years were treated with corticosteroids. Ten patients were treated with 6 cycles of CHOP-21 chemotherapy resulting in: 2/10 (20%) stable disease, 5/10 (50%) partial remission and 3/10 (30%) complete remission. The median EFS and OS of chemotherapy-treated patients were 8 and 10 months, resp. The EFS and OS were both significantly longer in patients who achieved complete remission within the first line of CHOP or autologous stem cells transplantation therapy: 43 vs 6 (p = 0.0052) and 46 vs 6 months (p = 0.0023), respectively. It was not possible to perform autologous transplantation in 4/7 (57%) patients in need for further reduction of the disease because of poor performance status or early progression of lymphoma and death during salvage chemotherapy. CONCLUSION: AITL is a poor prognosis malignancy with a very high risk of early relapse after CHOP induction chemotherapy. In fit patients, autologous transplantation should be performed immediately after induction chemotherapy; information about availability of stem cells donor, both in the family or any available register, should be found during the induction treatment.

[Patient with B-CLL with a history of unrelated hematopoietic cells donation--retrospective analysis of CLL development and implication for the recipient]. / Pacient s B-CLL s anamnézou darování krvetvorných bunek nepríbuznému pacientovi - retrospektivní sledování vývoje nemoci a dusledky pro príjemce.

BACKGROUND: Donor cell leukemia (DCL) is a relatively rare but well documented complication of hematopoietic stem cell transplantation. So far, publications described only DCL arising de novo in the recipient. OBSERVATION: In this study, we describe a case of chronic lymphocytic leukemia (B-CLL) developing in a volunteer unrelated donor from the Czech National Marrow Donors Registry (CNMDR) several years after donation. From archival DNA sample, we have retrospectively found that subclinical CLL clone was already present at the time of donation but early death of recipient prevented eventual development of DCL. This case documents well the long period between detection of B-CLL clone and full development of clinical-laboratory symptomatology. The medical and ethical questions posed by an isolated case of detection of hematological malignancy present either only in the donor or only in the recipient are discussed. CONCLUSION: The case demonstrates the increasing risk of development of various forms of DCL and thus highlights the need for long-term monitoring of stem cell donor, not only in terms of health of donor but also in terms of potential risks for the recipient.

[Diagnosis and treatment of BCR/ABL-negative myeloproliferative diseases--principles and rationale of CZEMP recommendations]. / Diagnostika a lécba BCR/ABL-negativních myeloproliferativních onemocnení--principy a výchdiska doporuceni CZEMP.

In 2009, the recommendations of the Czech Collaborative Group for Ph- Myeloproliferative Diseases (CZEMP) for diagnosis and treatment of BCR/ABL-negative myeloproliferative diseases (MPD), i.e., essential thrombocythemia (ET), polycythaemia vera (PV) and primary myelofibrosis (PMF) were updated and extended. The present article gives the rationale of the recommendations in full detail. The CZEMP diagnostic criteria for ET and PMF are based on histopathological (HP) findings, which must unconditionally be in line with the given clinical and laboratory characteristics of ET or of a certain stage of PMF, respectively. The platelet count is not decisive for diagnosis. In cases lacking an adequately taken and read HP finding, the Polycythemia Vera Study Group (PVSG) criteria are recommended. The diagnosis of typical PV is based on demonstration of the V617F mutation of the JAK2 gene along with a significant increase of red cell parameters. If these are close to borderline, the demonstration of increased total red cell mass (RCM) is required. In atypical cases lacking polyglobulia or elevated RCM, the HP picture of PV (in accordance with WHO description) plus JAK2 V617F mutation is satisfactory for diagnosis, or, in cases lacking JAK2 V617F mutation, the HP picture of PV along with polyglobulia (or increased RCM) is sufficient. The treatment principles of ET and other MPDs with thrombocythemia (MPD-T; i.e., the early stages of PMF and PV) are identical. The patients are stratified by their thrombotic risk (preceding thrombosis, another thrombophilic state, jAK2 mutation), presence of disease symptoms (mainly microcirculatory), platelet count and age. Only patients up to 65 years lacking the above mentioned risks with a platelet count < 1000 x 10(9)/l are considered as low-risk and do not demand cytoreducing therapy. The others are high-risk ones and have an indication for thromboreduction. In patients older than 65 years, the potentially leukemogenic drug hydroxyurea (HU) may be used. In the younger ones, the choice is between anagrelide (ANG) or interferon-alpha (IFN). In high-risk patients, the treatment goal is to maintain platelet counts below 400, and in low-risk ones, below 600 x 10(9)/l. In PV, polycythemia itself is another thrombotic risk factor. The condition is treated by bloodletting or erythrocytaphereses. If hematocrit levels < or =45 are not achieved, cytoreductive therapy using HU in patients over 65 years, or IFN in younger individuals is required. All patients with thrombocythemia in PV are high-risk and have an indication for cytoreduction. Acetylsalicylic acid is given to all patients with MPD-T with platelets < 1000 x 10(9)/l (at higher counts, hemorrhage is imminent), and to all individuals with PV, unless contraindication is present. In case of platelet count normalization, it may be withdrawn in cases of low-risk ET or PMF, not in JAK2+ PV. The treatment of advanced stages of PMF is symptomatic, with substitution of blood derivatives being the basis. The only curative treatment is allogeneic stem cell transplantation, which should not be indicated too early seeing to its risks, but also not too late--we must not allow transition into acute leukemia, which is heralded by blasts in the blood picture. The indication is the presence of any of the following criteria: values of hemoglobin < 10 g/dl, WBC < 4 x 10(9)/l and platelets < 100 x 10(9)/l, any percentage of blasts or > or = 10% immature granulocytes in the differential picture, >1 erythroblast per 100 cells--all at repeated examinations within at least a 2-month interval, and in addition, rapid progression of hepato-/splenomegaly, presence of general symptoms of the disease, portal hypertension and extensive swellings.

[The results of patients with essentials thrombocythemia and other myeloproliferation-related thrombocythemia--a report of patients treated with Thromboreductin]. / Výsledky lécby nemocných s esentiální trombocytemií a dalsími myeloproliferacemi provázenými trombocytemií--zpráva z registru pacientu lécených Thromboreductinem.

The registry of patients treated with Thromboreductin (anagrelide) in the Czech Republic contains data concerning patients that have been treated using this drug since 2004. As of June 2009, the total number of patients was 549. The current analysis focused mainly on evaluation of anagrelide dosage needed to achieve a complete response in high-risk patients: reduction in platelet count to below 400 x 10(9)/l, which was also considered as reaching the therapeutic goal. The outcomes of the registry confirm that although anagrelide (Thromboreductin) is a very effective platelet-reducing agent, the administration of which is related to a low incidence of adverse effects and complications, the therapeutic goal is not achieved in all cases and or despite a quick treatment response, the therapeutic goal is achieved more slowly.

[What is the current treatment of patients with essential thrombocytopenia and other myeloproliferations accompanied with thrombocythemia [corrected] and what can be the predictive sign of the risk of thrombosis in such patients--a report from the registry of patients treated by Thromboreductine]. / Jak lécíme nemocné s esenciální trombocytemií a dalsími myeloproliferacemi provázenými trombocytemií a co muze být prediktivní známkou rizika trombózy u techto nemocných--zpráva z registru pacientu lécených Thromboreductinem.

The registry of patients treated with Thromboreductine (anagrelid) in the contributing centres in the Czech Republic has been updated with data on the patients receiving this medication since 2004. The original purpose of the registry was to record responses to Thromboreductine therapy and adverse drug reactions in patients with essential thrombocytopenia. However, data on additional Ph negative myeloproliferations, as well as data on cytoreductive therapies other than exclusively that using Thromboreductine has also been recorded in the course of its compilation, including data on combined regimes. At present, the database contains data on 421 patients, and valid conclusions can be drawn if the level of data filling is enhanced. Evaluation has been currently focused on the analysis of the risk of development of clinical symptoms of thrombosis and on the standards of treatment from the viewpoint of the achieved treatment response. Analyses of data from the registry corroborate the special importance of the proof of JAK2 mutation, and of the test for factor V Leiden mutation, and of protein of S for the assessment of the risk of thromboembolic complications. The output of the analysis confirms that anagrelid is a very efficient thromboreductive agent the administration of which is associated with a low incidence of non-serious adverse effects (10.9%). However, in spite of a fast response to therapy, the therapeutic goal consisting in the reduction of the platelet count below 400 (or below 600) x 10(9)/l, i.e. the complete (or partial) treatment response, is relatively slow to achieve. This is likely to be due to lack of radical corrections in the dosage of the drug for different reasons.

[Essential thrombocytemia and other myeloproliferations with thrombocytemia in the data of the register of patients treated with Thromboreductin till the end of 2006]. / Esenciálni trombocytemie a dalsí myeloproliferace s trombocytemií v údajích registru pacientu lécených Thromboreductinem do konce roku 2006.

Since 2005, registers of patients treated with Thromboreductin (anagrelid) kept by some centres in the Czech Republic have been supplied with data concerning patients whose treatment with this preparation started in 2004. The purpose of the register is to record responses to therapy by Thromboreductin and adverse events in patients with essential thrombocytemia and other myeloproliferations, and to subsequently analyse the data. Another objective is to detect predisposition to clinical symptomatology and disease complications. Apart from thrombocyte count, additional risk factors are monitored. The database currently contains data for 336 patients. Initial analyses of data from the register point to the fact that anagrelid is a highly effective thromboreductive agent the administration of which is associated with relatively low incidence of adverse events (11.8 %) of mild and usually transitory nature. The therapeutic objective is attained at a relatively slow rate (according to overall stratification under 400 or under 600 x 10(9)/l thrombocytes), which is probably due to insufficient dose adjustment.

International Staging System required standardization of biochemical laboratory testing in multiple myeloma.

The standardization of biochemical measurement procedures in multiple myeloma is necessary for reliable prognostic stratification of patients in multicentric trials. The new prognostic index International Staging System for multiple myeloma uses only two laboratory markers, albumin and beta-2 microglobulin. Our study compared results of albumin, beta-2 microglobulin and monoclonal immunoglobulin measurements from six centers which provide treatment for multiple myeloma in the Czech Republic and attempted to standardize the analytic procedures. We have found that the measurement of albumin is well standardized and the results from all laboratories were comparable. The measurement of beta-2 microglobulin achieved comparability only after a partial unification of analytical methods. The determination of monoclonal immunoglobulin concentration provided comparable results for concentrations higher than 20 g/l with higher variability for lower values.

[Anagrelide in the treatment of essential thrombocythemia (ET) and other myeloproliferative disorders with thrombocythemia based on data from patient register in the CR]. / Anagrelid v lécbe esenciální trombocytemie a dalsích myeloproliferací s trombocytemií sledovaných v registru pacientu v CR.

Anagrelide hydrochloride is an effective drug used in patients with ET and other myeloproliferative disorders with thrombocythemia to selectively decrease the number of thrombocytes. Indications for use of anagrelide were described in detail in Czech medical literature. Since 2005 data concerning treatment with anagrelide in some medical clinics have been collected in patient register showing course of treatment from 2004, when the medicament obtained marketing authorization from State Institute for Drug Control to be used in the treatment of thrombocythemia in myeloproliferative disorders. Aim of patient register is to monitor medical effect of anagrelide therapy and incidence of adverse effects in patients with ET and other myeloproliferative disorders and subsequent analysis of collected data. At the moment patient register contains data from 154 patients.

[Recommendations for early identification of damage to the skeleton by malignant processes, and for early diagnosis of multiple myeloma]. / Doporucení pro casné rozpoznání postizení skeletu maligním procesem a pro casnou diagnostiku mnohocetného myelomu.

The number of newly diagnosed cases of multiple myeloma in the Czech Republic is about 3-4 per 100 000 persons per year. In the higher age groups, the incidence increases. Multiple myeloma is an illness that reacts well to treatment which can result in periods of remission lasting for years. Some of the patients are even able to return to work. A pre-requisite for successful treatment is early diagnosis and this is usually in the hands of first line physicians. This is the reason why the Czech Myeloma Group, in conjunction with neurologists, orthopedicians and radio diagnosticians has issued the following recommendations for first line physicians containing a more detailed description of the symptoms and the diagnostic pitfalls of the disease. This disease reminds a chameleon for the variety of its symptoms. For the sake of clarification, we shall divide multiple myeloma symptoms into five points, each of which is reason enough to warrant an examination to confirm or rule out a malignant cause of health problems (a negative result does not automatically mean exclusion). If any of the recommended examinations results positive, the diagnostic process must be continued, in which case a general practitioner refers the patient to a specialist health centre. Observing these recommendations should minimize the number of cases of late diagnosis. 1. Bone destruction symptoms. - Unexplained backache for more than one month in any part of spine even without nerve root irritability or without pain in other part of skeleton (ribs, hips, or long bones). - Pain at the beginning of myeloma disease is very similar to benigne common discopathy, however the intensity of backache is decreasing within one months in benigne disease. In the case of malignant process the intensity of bone pain is steadily increasing. - Immediate imaging and laboratory investigation are indicated by resting and night pain in spinal column or in any part of skeleton. - Backache with the sign of spinal cord or nerve compression should be sent for immediate X Ray, and focussed CT/MRI followed by acute surgery if needed. - Osteoporosis especially in men and premenopausal women. 2. Features of changed immunity or bone marrow function. Persistent and recurrent infection, typical is normochromic anaemia, with leucopenia and trombocytopenia. 3. Raised erythrocyte sedimentation rate even increase concentration of total plasma protein. 4. Impaired renal function. Increased level of creatinin or proteinuria, nephrotic syndrome with bilateral legs oedema. 5. Hypercalcemia with typical clinical symptoms (polyuria with dehydratation, constipation, nausea, low level conscience, coma). Every one from these points has to be reason for general medical doctor to start battery of tests: -X-ray of bones focused to painful area (mandatory before physiotherapy, local anaesthesia or other empiric therapy). If plain X-ray does not elucidate pain and symptoms are lasting more than one month, please consider all circumstances and results from laboratory investigation. This patient needs referral to the centre with MRI/CT facilities (CT or MRI is necessary investigation in case of nerve root or spine compression). -Investigation of erythrocyte sedimantion rate (high level of sedimentation of erythrocyte can indicate multiple myeloma). -Full blood count. -Basic biochemical investigation serum and urine: serum urea, creatinin, ionts including calcium, total protein, and albumin CRP (high concentration of total protein indicates myeloma, low level of albumin indicates general pathological process, similary increased concentration of fibrinogen, impaired renal function indicates myeloma kidney, however hypercalcemia is typical for highly aggressive myeloma). -Quantitative screening for IgG, IgM and IgA in serum (isolated raised level one of immunoglobulin with decreased level of the others indicates myeloma). -Common electrophoresis of serum is able to detect monoclonal immunoglobulin level at few gramm concentration. If all the laboratory investigation are in normal level the possibility that the current problems are multiple myeloma origine is smaller, but it does not exclude one of rare variant--non secretory myeloma (undifferentiated plasmocyt lost characteristic feature to produce monoclonal immunoglobulin). If any of tests indicate the possibility of myeloma, patient require urgent specialist referral to department with possibility to make diagnosis of malignant myeloma.

[Bortezomib (Velcade) in relapsed/refractory multiple myeloma--the first experience in the Czech Republic]. / Inhibitor proteazomu--bortezomib (Velcade)--v lécbe refrakterního mnohocetného myelomu První zkusenosti v Ceské republice.

BACKGROUND: Multiple myeloma is the second most prevalent and mostly fatal hematologic cancer. Further advances have been made in understanding the mechanisms involved in the myeloma pathogenesis and elucidation of critical signalling pathways as therapeutical targets. Proteasome inhibitors are the example of this new approach and bortezomib is the first agent in this class to enter clinical trials. METHODS AND RESULTS: In 6 hematological centers in Czech Republic 29 patients with refractory/relapsed myeloma had been treated with bortezomib (Velcade, Millennium Pharmaceuticals) in 2004. The initial dose 1.3 mg/m2 of Velcade was given, in 1 case the dose was adjusted due to pre-existing renal failure to 1 mg/m2. The response was achieved in 17 patients (59%). Four patients had complete, 11 partial and two minor responses. In 5 cases stabilization of disease was observed and 6 patients progressed during the therapy. CONCLUSIONS: Unfortunately, one patient died immediately after the start of therapy due to sepsis. The most common adverse events were thrombocytopenia, anaemia, neuropathy, gastrointestinal complication, renal failure and fatigue. Grade 4 adverse events occurred in 37.9% of patients (4x thrombocytopenia, 2x gastrointestinal, 2x renal failure, 1x sepsis, leucopenia, hepatopathy and anaemia, respectively). Peripheral neuropathic pain of grade 3 was reported in 4 cases, in one patient therapy had to be interrupted due to this complication. We confirmed promising results of phase II trials.

Mobilization of peripheral blood stem cells in CLL patients after front-line fludarabine treatment.

Autologous peripheral blood stem cell transplantation is performed in an increasing number of chronic lymphocytic leukaemia (CLL) patients who are in the first remission following fludarabine treatment. There are contradictory data about the adverse impact of fludarabine on stem cell harvest. We analysed retrospectively mobilization results in 56 poor-risk CLL patients (median age: 56 years) who underwent first-line treatment with fludarabine and cyclophosphamide. The mobilization, consisting of cyclophosphamide 3 g/m(2) and granulocyte colony-stimulating factor (G-CSF) 10 microg/kg per day, was performed with a median of 77 days following the last fludarabine course. The target yield was >or=2.0x10(6) CD34+ cells/kg. The procedure was successful in 23 (41%) patients. A median of 3.3x10(6) CD34+ cells/kg was collected per patient. The successful mobilization was associated with a longer interval from the last chemotherapy (>2 months). The mobilization result was not influenced by the number of fludarabine cycles. No correlation was found in other parameters such as disease stage at diagnosis, disease status at stimulation or age. The poorly mobilized patients had significantly lower prestimulation blood counts (platelets, WBC and haemoglobin). Our data show that fludarabine does not generally prevent the stem cell mobilization; nevertheless, mechanisms related to the impact of fludarabine on stem cell harvest must be further investigated.

[Quality of life and tolerance of maintenance therapy in patients with multiple myeloma]. / Kvalita zivota a tolerance udrzovací lécby u pacientu s mnohocetným myelomem. Ceska myelomova skupina.

Questionnaires on the quality of life and tolerance of different parts of maintenance treatment were sent to a total of 83 patients with multiple myeloma. All patients were for more than one year on maintenance treatment which involved either interferon alpha monotherapy (I), 3 million u. three times per week till signs of relapse developed or sequence administration of interferon alpha and dexamethazone 40 mg on day 1 to 4, 10 to 13 and 20 to 23 and then after a four-week interval again interferon alpha, again till progression of the disease occurred. The patients evaluated the presence or absence of different undesirable effects of treatment during the first two weeks of treatment and throughout the year and listed their intensity into four categories defined in the questionnaire. The quality of life was evaluated by means of a basic module of the questionnaire of the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30). The results of the questionnaire are to a certain extent surprising as from the patients' answers ensues that this maintenance treatment is associated with more numerous undesirable effects than the physicians realized when in contact with the patient. In this summary we can list only the most frequent effects (deterioration of eyesight, impaired sleep, depressions, irritability and unrest, chill, pain in muscles and joints, general weakness and dyspnoea). From the questionnaires on the quality of life ensues a markedly poorer quality of life of these patients as compared with the healthy population. There are however no basic differences between individual groups. The questionnaires were handed only to patients who had maintenance treatment for more than one year and thus patients were eliminated where maintenance treatment was discontinued because of undesirable effects. To give a general idea of the tolerance of the above maintenance treatment the authors mention that to the date of Aug. 31, 2001 113 patients were randomized into one of the branches of maintenance treatment. Maintenance treatment had to be discontinued in 6% patients (in two instances on account of severe hypothyroidism, in one case on account of hallucinations, in three instances on account of severe mental depression caused by this treatment). Reduction of interferon doses in 20% patients usually because of cytopenia but also on account of psychic problem. To the question what length of prolongation of life compensates the undesirable effects of maintenance treatment the following replies were obtained from patients receiving ID, possibly I: 3 months--47.6 and 38.3%, 6 months--4.3 and 10.6%, 9 months--0 and 4.3%, 12 months--47.6 and 46.8% of the addressed patients. In reply to the question whether the patients would prefer, assuming equal effectiveness, a maintenance monotherapy with interferon alpha or dexamethazone more patients preferred interferon to dexamethasone. For practice ensues from this article informing on undesirable effects of maintenance treatment and the effect of maintenance treatment on the quality of life: 1. the necessity of thorough knowledge of physicians of all possible undesirable effects as only a doctor knowing possible undesirable effects of treatment can recognize them, 2. regular monitoring not only of the activity of the basic disease, but also undesirable effects of maintenance treatment and the influence of treatment on the patients' quality of life, 3. the necessity to assess the quality of life in clinical trials as an important parameter for deciding on the way of treatment.

[Allogenic transplantation of bone marrow in patients with chronic myeloid leukemia 1991-1995 and 1996-1998. Experience at the Hematology-Oncology Clinic of the University Hospital in Plzen]. / Alogenní transplantace kostní drene u pacientu s chronickou myeloidní leukémií v období 1991-1995 a 1996-1998. Zkusenosti Hematologicko-onkologického oddelení FN Plzen.

The authors compare the results of allogenic bone marrow transplantations of relatives in patients with chronic myeloid leukaemia during the initial years of the transplantation programme 1991-1995 (group 1, 15 patients) with results achieved in 1996-1998 (group 2, 30 patients) and evaluate the effect of changes concerning supportive treatment and new diagnostic methods. The age median of group 1 was 35 years, the median age of group 2 46 years. In other parameters the groups were comparable. In 1991-1995 a high transplantation mortality by the 100th day was recorded (40% as compared with 17%) and a higher incidence of stage III and IV of the acute reaction of the graft against the host (GVHD) in group 1 (20% vs. 6%). In group 2 there was a higher transplantation mortality after day 100 associated with a more frequent chronic GVHD (0% vs. 16.5%). The total survival is insignificantly better in group 2 (60% in group 1 survive with a median of 58 months follow up and 67% of group 2 with a median follow up of 33 months). Group 2 comprises however older patients. In the improved early transplantation mortality participated new methods, a change of the posttransplantation immunosuppression, experience with care of transplanted patients and better collaboration with other medical disciplines. The authors did not observe a substantial effect of changes in the basic supportive treatment on results of transplantation. Late transplantation mortality associated in particular with a higher incidence of chronic GVHD could be in the authors' opinion reduced by longer administration of immunosuppression after transplantation, in particular in older patients.

[Autologous transplantation of peripheral hematopoietic cells and subsequent maintenance therapy with interferon alpha or interferon alpha and dexamethasone in patients with multiple myeloma--results from the 4W randomized clinical trial of the Czech Myeloma Group]. / Autologní transplantace periferních hemopoetických bunek a následná udrzovací terapie interferonem alfa nebo interferonem alfa a dexamethasonem u nemocných s mnohocetným myelomem--prubezné výsledky randomizované klinické studie 4W Ceské myelomové skupiny.

In the clinical 4W study patients with newly diagnosed multiple myeloma are included where the state of the disease calls for treatment, while high dose chemotherapy is not contraindicated. Treatment according to protocol 4W comprises induction chemotherapy VAD, mobilization of haematopoietic cells (cyclophosphamide 5 g/m2). This is followed by autologous transplantation (as a conditioning regime melfalan 200 mg/m2 is administered). The patients are randomized into two groups, the first one is given interferon alpha as maintenance treatment, in the second group alternates cyclically interferon alpha and dexamethasone treatment. So far between 1996 and Aug. 31 2000 in the 4W clinical study 167 patients were included. 113 patients after transplantation were evaluated incl. 13 (12%) who achieved complete remission of the disease (absence of paraprotein, negative immunofixation), 63 patients (56%) with remission of the disease (decline of paraprotein, by more than 75%). Another 24 patients (21%) achieved partial remission (decline of paraprotein by more than 50% but less than 75%). The peritransplantation mortality is 2.67%. So far there is no significant difference between the two groups on maintenance treatment as regards the mean period before a relapse of the disease (p = 0.567). The median of the mean survival was not reached so far. The authors describe the results of the internal analysis of data incl. statistical processing.

Allogeneic BMT in patients above 45 years of age: a single center experience.

Increasing age has been reported to be associated with worse outcome and higher occurrence of complication after allogeneic bone marrow transplantation. We analysed a cohort of 39 patients between the ages of 45 and 57 (median 49 years) with different hematologic malignancies who had undergone BMT in our institution over the preceding 4 years. Pretransplant conditioning consisted of Bu/CY2, GVHD prophylaxis of a combination of cyclosporine and "short" methotrexate. At present 54% of patients remain alive (with a median follow-up 44 months), the probability of survival at 5 years is 53% (5-year DFS 78%). The 5-year survival probability in the control group of younger patients is 53% (P = 0.8003). Main causes of death were GVHD (4 patients, 10%), relapse (5 patients, 13%) and infection (6 patients, 15%). The incidence of acute GVHD grade II-IV was 51% (grade III-IV 0% patients), the incidence of chronic GVHD 49% (limited 18% and extensive 31% patients). Our results suggest that allogeneic BMT can be performed in patients above the age of 45 years with acceptable morbidity and mortality, especially if a family HLA matched donor is available.