Megakaryocyte colony-forming unit growth is enhanced by alemtuzumab: in vitro experiments and a case report of acquired amegakaryocytic thrombocytopenic purpura.
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Antineoplastic Agents↗
Biomedical subjects
Z Korístek
Publications and source records attributed to Z Korístek.
[Incidence of selected antiphospholipid antibodies in a group of patients with systemic lupus erythematosus].
Antiphospholipid antibodies (APLA) present very heterogeneous groups of antibodies which can significantly and in various ways influence processes on different levels of coagulation cascade. Their presence can be accompanied with repetitive venous and arterial thromboses, recurrent loses of foetus, and thrombocytopenia. Incidence of these thrombotic disorders was monitored in a group of 46 patients with systemic lupus erythematodes (SLE). Positive lupus anticoagulant (LA), antiphospholipid antibodies complex, and thrombocyte counts were assessed. Thrombotic disorders were assessed in a retrospective analysis. In the LA+ group 62% of patients had history of venous thromboses, 31% had history of arterial thromboses, and 18% had history of spontaneous abortions. In a group without positive LA 18% of venous thromboses (p = 0.0006) and 6% of arterial thromboses (p = 0.03) were indicated. In the assessment of spontaneous abortions no statistically significant difference was found. An average value of thrombocytes in LA+ group was 152 +/- 66 x 10(5)/l, in LA- group 223 +/- 86 x 10(5)/l, which is statistically significant difference (p < 0.05). In the assessment of thrombotic disorders in a group with combination LA+ and APA+ statistical significance was indicated only in venous thromboses (p = 0.004). We can state from the results that in thrombotic disorders which can be seen in the framework of systemic tissue disorders positive LA and APA and a range of other factors such as activity of a basic disease, associated diseases, and treatment which can aggravate thrombotic disorders of individual patients can participate.
Abortion, Spontaneous↗
[Evaluation of the clinical effectivity and toxicity of the FDN regimen (fludarabin, mitoxantron, dexamethason) in patients with follicular lymphoma].
BACKGROUND: One of the perspective therapeutic possibilities in follicular lymphomas (FL) is the fludarabine-based regimen FND (fludarabine, mitoxantron, dexamethason). However serious signs of myelotoxicity and significant immunosuppression with appearance of the opportunistic infections were described after the fludarabine treatment. METHODS AND RESULTS: Follicular lymphoma patients with advanced disease grade I-II were treated with FND (6-8 cycles). The immunotoxicity was evaluated by measuring of immunoglobuline levels (IgA, IgG, IgM) and that of lymphocytes subpopulations (CD3+, CD4+, CD8+, CD20+, CD56+) in peripheral blood. The myelotoxicity was evaluated by cultures of progenitor cells (CFC and LTC-IC). Totally 34 patients (median age 55.5 years) were evaluated, the overall response was 72% (CR 61%, PR 11%, progression 28%). 73% patients of 11 after 6-8 FND show persisting CR (27% relapsed) with median follow-up about 15 months. The dominating toxicity was myelotoxicity. The leucopenia grade III-IV occurred in about 30% cycles. Because of toxicity it was necessary to reduce doses of FND in 10% cycles and this treatment had to be finished ahead of schedule in 29% patients. The significant immunotoxicity was found only in the decrease of whole lymphocyte population (p < 0.05) and of IgG level (p < 0.05). The decrease of lymphocyte subpopulations did not reach any statistical significance. The long-term myelotoxicity caused the decrease of LTC-IC that had a clinical correlation with the very difficult mobilization of PBSC. CONCLUSIONS: FND is efficient in treatment of follicular lymphoma. However myelotoxicity seems to be limiting. Myelotoxicity doesn't allow administering scheduled dose of FND in substantial amount of patients, long-term myelotoxicity complicates PBSC-mobilization. Lymphotoxicity is apparent, but seems not to be clinically important.
Adult↗
Mathematical model of peripheral blood stem cell harvest kinetics.
A mathematical model of peripheral blood stem cell harvests was developed, taking two new parameters R (number of recruited cells/minute) and E(f) (efficiency of collection) into consideration in addition to concentrations and collected amounts of cells. This model was tested on 241 harvest procedures in cancer patients (chemotherapy+G-CSF stimulation), donors of allogeneic PBSC, and platelet donors, using different collection procedures, with a Cobe Spectra Cell separator. The relationships between preapheresis concentrations, R, E(f) and harvested amounts of cells were complex, and different for different harvest procedures and populations of donors. However, invariably, recruitment played an important role and contributed significantly to the final harvest in all types of cells studied. For example, for the patient group, mean recruitment was 1.3 x 10(6) CD34+ cells/min and the amount of recruited cells corresponded to 65% of all collected cells. Recruitment was significantly influenced by pretreatment with chemo-therapy and/or radiotherapy. The mean recruitment values for the subgroups with limited, moderate, and extensive pretreatment were 1.65 x 10(6), 0.87 x 10(6), and 0.32 x 10(6) CD34+ cells released per minute, respectively. The finding of a quick and massive recruitment phenomenon may stimulate further research into hematopoiesis in order to maximize harvested cells.
Blood Component Removal↗
[Analysis of phenotypes and kinetics of CD34+ cells and lymphocytes in donors of hematopoietic stem cells for allogenic transplantation].
BACKGROUND: Amount of CD34+ cells is a critical parameter for quality assessment and successful engraftment of peripheral blood hematopoietic stem cells (PBSC) during the transplantation of haemopoisis. CD34+ cells are routinely analysed by immunophenotyping in PBSC and in peripheral blood during mobilization. Other leukocyte subpopulations are not usually assessed. METHODS AND RESULTS: The authors present results of immunophenotyping of subpopulations of CD34+ cells and leucocytes in samples from donors of PBSC for allogeneic transplantations, who were stimulated with the growth factor G-CSF at dose 16 micrograms/kg/day. The amount of CD34+ cells was not significantly different between days 4 and 5; however, there was a significant drop at day 6. CD34+90+ and CD34+61+ subpopulations reached their maximum at the day 4; partially differentiated CD34+ cells with co-expression of CD33, CD19, and CD7 reached maximum at the day 6. CD4+ Th-lymphocytes were concentrated in the grafts during leukapheresis, CD4/CD8 ratio in the grafts was increased to average 3.06. CONCLUSIONS: The knowledge of kinetics of CD34+ subpopulations, together with stem cell selection and ex vivo manipulation, may have an impact on the speed of engraftment or GvHD prevention in transplanted patients.
Antigens, CD34↗
[Treatment of acute lymphoblastic leukemia in adults with seven-drug induction therapy and intensive consolidation with or without autologous stem cell transplantation followed by maintenance therapy. Experience of a single center].
BACKGROUND: During the last few years, improvement in prognosis of the adult acute lymphoblastic leukaemia (ALL) has been modest. The probability of leukemia-free survival is 20-40%. Philadelphia-chromosome positive (BCR-ABL positive) ALL has the worse prognosis. A single centre experience with treatment of ALL in adults is reported. METHODS AND RESULTS: Between April 1997 and July 2000, 15 consecutive patients with de novo adult ALL (7 T-lineage ALL, 7 B-lineage ALL, 1 null ALL) begin their treatment with the seven-drug induction regimen (in phase I, daunorubicin, vincristine, L-asparaginase, i.v., and prednisone, p.o.; in phase II, 6-mercaptopurine, p.o., cytosine arabinoside and cyclophosphamide, i.v.) and central nervous system (CNS) prophylaxis (methotrexate and CNS irradiation in patients without total body irradiation in conditioning regimen), with intensive consolidation (three times high-dose methotrexate and high-dose-cytarabine, i.v.), and with/out autologous peripheral blood stem cell transplantation (PBSCT) followed by maintenance chemotherapy (6-mercaptopurine and methotrexate, p.o.). Seven patients received autologous PBSCT. Median patient age was 30 years. Three patients were BCR-ABL positive at diagnosis. With median follow-up 14 month (range 0.1-46 month), seven (4 T-lineage ALL, 2 B-lineage ALL, 1 null ALL) out of 15 patients are alive in remission (four of them receiving autologous PBSCT). Causes of death were relapse (n = 3), chemotherapy related toxicity (n = 2), infection (n = 1), and acute myeloid leukaemia developed 10 months after autologous PBSCT (n = 1). All BCR-ABL positive patients died. CONCLUSIONS: Chemotherapy alone and autologous PBSCT with maintenance therapy may be curative for adult patients with ALL. We can recommend these treatment options for patients without risk factors in particular.
Adolescent↗
Technique for PBSC harvesting in children of weight under 10 kg.
Peripheral blood stem cell (PBSC) harvesting in the smallest children (weight <10 kg) using separators is complicated by specific problems. The volume of the separation set exceeds 25% of the total blood volume and the vascular access is generally not sufficient. Therefore, a simple manual technique for PBSC harvesting was developed. Three children (6-9 kg), with newly diagnosed tumours were scheduled to be treated with three to six sequential courses of high-dose chemotherapy, each followed by PBSC support. PBSC harvests were started after mobilization using cyclophosphamide and G-CSF when the peripheral blood CD34+ cell count exceeded 50/microl. About 50 ml of blood was drawn from a venous catheter, injected into a transfer bag containing ACD-A, and centrifuged. The buffy coat obtained was pooled in a collection bag, remaining plasma and erythrocytes were immediately reinfused and a subsequent cycle started. From three to 13 cycles were performed in 1-3 days and 18.0-32.2 x 10(6) CD34+cells/kg were collected. We did not detect any bacterial contamination or any notable complications. Fifteen PBSC reinfusions have been performed to date, each with rapid engraftment taking between 7 and 13 days. Patients are in very good PR (18 months from diagnosis) or in CR (6 and 8 months). We can conclude that this procedure is feasible and safe.
Antigens, CD34↗
Interleukin-2 activation of haematopoietic stem cells.
BACKGROUND: Recent findings concerning the role of immunity in the eradication of residual malignant disease after autologous haematopoietic stem cell transplantation have led to extensive studies of T-cell and natural killer (NK) mediated anti-tumour effects. Interleukin 2 (IL-2) activation of autologous bone marrow (BM) or peripheral blood stem cells (PBSC) before transplantation is one of the methods of adoptive cell therapy. METHODS: Autologous BM of patients with chronic myelogenous leukaemia (n = 11) and PBSC of patients with multiple myeloma (n = 14) were activated by IL-2 in laboratory conditions with the aim of evaluating the feasibility of this method, the activation of T and NK cells, recovery of active progenitor cells, microbial contamination, and reduction of malignant cell content. RESULTS: Samples of BM (mean 2.6 x 10(6) cells) and PBSC (mean 10.3 x 10(6) cells) were cultured in complete culture medium with IL-2 (6000 Ul/ml) for 24 h. The recovery of CD34+ cells and CFU-GM was 82.5% and 51.5%, respectively, for BM, and 85% and 86%, respectively, for PBSC (mean values). No purging effect was detected by flow cytometry and a small decline in malignant cell contamination was observed by quantitative PCR in BM samples. No microbial contamination occurred during the sample processing. CONCLUSIONS: The described in vitro activation of BM and peripheral blood stem cells using IL-2 was evaluated as a safe and reliable method suitable for clinical application.
Bone Marrow↗
[Activation of autologous hematopoietic stem cell transplants with interleukin-2].
BACKGROUND: Recent findings of the role of the immunity in eradication of residual tumour tissue after autologous transplantation rejection leading to extensive studies on T-cell mediated specific antitumor effects or nonspecific NL-cell mediated anticancer effects. We have evaluated on the methods of adoptive cell therapy--IL-2 activation of autologous graft in the preclinical conditions. In laboratory conditions we have manipulated with autologous grafts form patients suffering with chronic myelocytic leukemia and patients suffering with multiple myeloma. METHODS AND RESULTS: Autologous graft was activated with IL-2 during 24-hours cultivation period in X-Vivo 10 medium with heparine, glutamine and Dnase. Quality of grafts after cultivation, contamination and activation of T and NK cell were evaluated. No significant differences between IL-2 activated graft and control were found. Results of autologous graft quality (CD34+, CFU-GM) were comparable with already published results. Quality of final product allowed starting of clinical experimental trials. CONCLUSIONS: We have proved the possibility to use IL-2 activated autologous graft in the clinical conditions. Based on our preclinical results experimental clinical trials have been initiated in patients suffering from chronic myelocytic leukemia and multiple myeloma.
Cells, Cultured↗
Ifosfamide- and etoposide-based chemotherapy as salvage and mobilizing regimens for poor prognosis lymphoma.
Treatment of early relapsing or resistant non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) remains problematic. High-dose chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation improves the prognosis for patients in response following standard dose regimens. We adopted the strategy of using salvage chemotherapy to debulk disease and simultaneously mobilize stem cells. We used regimens based on ifosfamide and etoposide because these drugs are not usually used as the front-line treatment. Twenty-seven patients with NHL received MINE chemotherapy (mesna and ifosfamide 1330 mg/m2 and etoposide 65 mg/m2 i.v. days 1-3, and mitoxantrone 8 mg/m2 i.v. day 1). The same schedule, but higher doses were used for PBSC stimulation (mesna, ifosfamide 1700 mg/m2, etoposide 175 mg/m2, mitoxantrone 10 mg/m2). Forty-six patients with HD received VIM chemotherapy (mesna, ifosfamide 1200 mg/m2 i.v. days 1-5, etoposide 90 mg/m2 i.v. days 1, 3, and 5, methotrexate 30 mg/m2 i.v. days 1 and 5). After both VIM and high dose MINE, chemotherapy for mobilization was followed by G-CSF administered at a dose 5-16 micrograms/kg/day depending on the clinicians judgement of the patient's pretreatment. Complete response after VIM and MINE were 39% and 38%, respectively; partial response (PR) rates were 17% and 29%, and stable disease (SD) 25% and 4%, respectively. In both groups, patients with relapsing disease had better responses than did those with primary progressive disease. Both regimens exhibited excellent mobilizing capacity. We performed 213 aphereses with a median 3 per patient starting on either day 13 as a median for VIM, or on day 12 as a median for MINE. In the majority of patients, the collection started in the time interval median +/- 1 day (n = 62, 85%). The median yields were 10.6 x 10(6) CD34+ cells/kg and 53.1 x 10(4) CFU-GM/kg for VIM, and 13.3 x 10(6) CD34+ cells/kg and 54.5 x 10(4) CFU-GM/kg for MINE. We collected at least 2.5 x 10(6) CD34+ cells/kg in all but six patients (8%), and the harvested amount of CD34+ cells was less than 1.0 x 10(6)/kg in only two patients (3%). The toxicity of VIM and MINE was minimal and chemotherapy-induced trombocytopenia did not occur with PBSC collection.
Adolescent↗
[Collection of peripheral hematopoietic stem cells for transplantation from volunteer donors--siblings of the patients].
Peripheral stem cells obtained by stimulation of haematopoiesis by administration of so-called growth factors are used for allogenic transplantations of haematopoietic cells only since the mid-nineties of the 20th century. So far however not all potential undesirable effects of growth factor administration to healthy subjects are known. The authors present the results of a programme of allogene transplantation of peripheral blood stem cells from related donors which was started in their department in 1996. From 11/1996 till 8/2000 the authors started 55 mobilizations of peripheral stem cells in donors before transplantation. The mobilization growth factor G-CSF was used for in a total dose of 16 micrograms/kg/day s.c. administered in two daily doses. During administration of G-CSF 19 donors had no complaints, 34 donors (64%) had pain in their bones, subfebrile temperatures and/or symptoms of flu. G-CSF produced dramatic changes in the haemogram--massive leucocytosis with dominant neutrophilia, after collection of the transplant thrombocytopenia developed. The changes of some biochemical parameters were also marked. A peripheral venous approach for collection of the transplant was applied in 23 instances (43%), in the remainder cannulation of a central vein was used. A total of 121 leukaophereses was performed in 53 donors (separator COBE Spectra) which were started on the 4th day of G-CSF administration. An automatic operation of PBSC collection was used in 28 leukaphereses, an operation of mononuclear collection in 93 leukaphereses. In leukaphereses only mild symptoms of hypocalcaemia were observed in 26 donors (48%). The mean total yield of leukaphereses was 9.39 x 10(6) CD34+ cells/kg of the recipient (3.48-23.13) and 76.54 x 10(4) CFU-GM/kg of the recipient (10.02-238.78), no mobilization failed. Of 36 donors 25 (69%) came for a check-up one year after collection of the transplant. No changes in the haemogram nor in biochemical parameters were recorded. In donors with hepatopathies pathological findings persisted in biochemical examinations without a deteriorating trend. Administration of G-CSF to healthy subjects is a new technology associated with certain advantages as well as some questions. Safety of donors holds the first place, detailed information is essential as well as examination and follow up not only on a short-term but also on a long-term basis.
Adult↗
[Haematopoietic stem cell mobilization in patients with multiple myeloma--comparison of 3 variations of the stimulating regime].
In the literature various regimes are described for successful collection of haematopoietic stem cells in patients with multiple myeloma. Most frequently cyclophosphamide is used, 5 g/m2 combined with different doses of haematopoietic growth factors. In our group the yields and tolerance of three stimulating regimes are compared: 1. cyclophosphamide 5 g/m2 and filgrastim (G-CSF) 5 micrograms/kg 2. cyclophosphamide 5 mg/m2 and filgrastim 10 micrograms/kg 3. cyclophosphamide 5 g/m2 and figrastim 5 micrograms/kg along with erythropoitin 50 IU/kg. Cyclophsphamide is administered always on the first day and the haematopoietic growth factors then from the third day till the end of collection of haematopoitic cells. In patients with multiple myeloma where only four cycles of VAD chemotherapy preceded and where radiotherapy of the axial skeleton was not used, optimal collection of haematopoietic stem cells was achieved after administration of cyclohosphamide 5 g/m2 with subsequent administration of 5 micrograms/kg G-CSF. By increasing the dose of G-CSF to 10 micrograms/kg or adding 50 IU/kg erthropoietin did not lead to a significant improvement of the tolerance and yield of this procedure.
Cyclophosphamide↗
[Effect of high-dose chemotherapy in patients with relapsing or resistant Hodgkin's disease].
The authors evaluated a group of 48 patients with relapsing or resistant Hodgkin's disease. The patients were treated by life-saving chemotherapy followed by large doses of chemotherapy and autologous transplantation of haematopoietic cells. For life-saving chemotherapy they used most frequently a combination of VIM in 40 patients and combinations of DHAP, MINE, MiniDexaBEAM. In 11 patients they changed the regime of life-saving chemotherapy because of a poor response. After completed life-saving chemotherapy 18 (37.5%) patients were in CR, 27 (56.2%) in PR and in 3 (6.3%) the disease progressed. For large dose chemotherapy the authors used BEAM in 32 patients, CBV in 2, Busulfan with Cyclophosphamide in 13 patients and Busulfan with Melfalan in one patient. After completion of large dose chemotherapy and subsequent autologous transplantation of bone marrow 31 (64.6%) patients were in CR, 8 (16.7%) in PR and the disease progressed in 9 (18.7%). In August 1999 a total of 44.9% patients in CR survive, the median period of follow up after autologous transplantation was 23 months. Life-saving chemotherapy with subsequent large dose chemotherapy led in the investigated group to induction of CR in 64.6% patients which is the basic prerequisite of long-term survival.
Adult↗
[Kinetics of hematopoiesis after high-dose chemotherapy and autologous peripheral stem cell transplantation].
BACKGROUND: Autologous peripheral blood stem cell transplantation (APBSCT) is gradually replacing autologous bone marrow transplantation in many clinical settings. The key question is how to evaluate the quality of grafts. We analyzed the relationship between hematopoietic reconstitution and characteristics of patients and grafts. METHODS AND RESULTS: Data from 95 APBSCTs were analyzed. Peripheral stem cells were obtained after mobilization using anti-neoplastic chemotherapy followed by Neupogen (G-CSF). After high dose chemotherapy and APBSCT, patients received Leucomax (GM-CSF). Patients were reinfused with a median of 6.1 x 10(6) (range 0.83-29.3) CD34+ cells/kg, and 25.1 x 10(4) (range 1.0-167.0) CFU-GM/kg of body weight. The median time to engraftment was 12 days (both for granulocytes 1 x 10(9)/l and platelets 50 x 10(9)/l). We found a significant correlation between the number of CD34+ cells and CFU-GM reinfused and also between their respective graft sizes and time to leukocytes, platelets, and granulocytes recovery. We did not find a significant correlation between the number of mononuclear cells reinfused and any analyzed parameter (time to engraftment, age, diagnosis, number of previous chemotherapies, type of mobilization or high-dose regimen). However, administration of preparative high-dose chemotherapy consisted of busulphan and cyclophosphamide was associated with the risk of a transient secondary graft failure. CONCLUSIONS: We conclude that the content of progenitors in PBSC grafts and time to booth leukocyte and platelet recovery are best estimated by the number of CD34+ cells (not less than 1 x 10(6)/kg) and CFU-GM (not less than 1 x 10(4)/kg). The number of mononuclear cells in an autologous PBSC graft is not suitable and useful for prediction of engraftment rate. There is probably no additional benefit of reinfusion of more than 8-10 x 10(6) CD34+ cells/kg and/or 50 x 10(4) CFU-GM/kg, because hematopoietic recovery is not more rapid.
Adolescent↗
Ifosfamide and etoposide-based chemotherapy as salvage and mobilizing regimens for poor prognosis lymphoma.
We treated 40 patients with poor prognosis lymphomas. Patients with non-Hodgkin's lymphoma (NHL, n = 14) received MINE chemotherapy (mesna, ifosfamide 1330 mg/m2 and etoposide 65 mg/m2 by i.v. infusions on days 1-3, mitoxantrone 8 mg/m2 i.v. on day 1), and those with Hodgkin's disease (HD, n = 26) received VIM chemotherapy (mesna, ifosfamide 1200 mg/m2 by i.v. infusion on days 1-5, etoposide 90 mg/m2 by i.v. infusion on days 1, 3 and 5, and methotrexate 30 mg/m2 i.v. on days 1 and 5). Chemotherapy was followed by G-CSF (10 or 16 microg/kg in two divided doses daily) to mobilize PBSC. We performed 134 aphereses (median three leukaphereses per patient) starting on either day 13 (median; VIM) or day 12 (median; MINE). The median yield was 9.9x10(6) CD34+ cells/kg and 53.2x10(4) CFU-GM/kg for VIM, and 13.5x10(6) CD34+ cells/kg and 53.4x10(4) CFU-GM/kg for MINE. Except for predictable myelosuppression, no serious toxicity was seen. Response rate using MINE was 63% (18% CR, 45% PR) and using VIM 50% (17% CR, 33% PR). We conclude that VIM and MINE are effective and well-tolerated salvage regimens in patients with lymphomas and, followed by G-CSF, they also exhibit good capacity to mobilize stem cells in a predictable time interval.
Adolescent↗
Bone marrow processing for transplantation using the COBE spectra cell separator.
BM processing, volume reduction, and granulocyte and erythrocyte depletion are important considerations for minimizing the side effects of graft administration and bypassing ABO incompatibility in allogeneic BMT. We used the COBE Spectra cell separator for BM processing in 33 patients suffering from hematologic malignancy and solid tumor (median age 39 years). We processed 42 BM harvests with the aim of maximizing recovery of mononuclear cells (MNC). BM was collected from the posterior iliac crest under general anesthesia. The mean volume of collected BM before filtration was 1,303 ml, and the mean number of collected total nucleated cells (TNC) was 2.61 x 10(8)/kg. The BM processing resulted in a mean recovery of 35.8% (10.1%-78.3%) TNC, 22.3% (1.1%-75.7%) of granulocytes, 78.8% (34.3%-135.2%) of MNC, 77.2% (8.3%-260.0%) of CD34+ cells, and 153.3% (32.9%-464.0%) of colony-forming units (CFU-GM) in the final product. A mean of 98.2% (94.5%-99.5%) of RBC was removed, with a mean of 13.3 ml (5.1-26.2 ml) of RBC in the final product. BM processing using the COBE Spectra cell separator proved to be fast, safe, and effective. However, the reasons for the very wide range of recovery of harvested CD34+ cells and CFU-GM need to be further investigated.
Adult↗
[Chemotherapy of resistant and recurrent lymphoma based on a combination of ifosfamide and etoposide. Antitumor effects, toxicity and stimulation of peripheral stem cells].
BACKGROUND: Treatment of Hodgkin's disease (HD) and non-Hodgkin lymphomas (NHL) is still unsatisfactory in patients resistant to primary therapy or those with early relapses. The objective of the trial was to test whether salvage regimens based on a combination of iphosphamide and etopozide have a sufficient anti-lymphoma effect, while the toxicity is still acceptable, and in conjunction with growth factors as satisfactory mobilizing potential for the collection of peripheral stem cells (PBSC). METHODS AND RESULTS: A group of 40 patients with relapsing and/or primary therapy resisting lymphomas (14 NHL, 26 HD) were treated by life saving or stimulating chemotherapy VIM (etopozide, iphosphamide, methotrexate) and MINE (iphosphamide mitoxanthrone, etopozide; mostly NHL). If the response to these regimes was inadequate, to some patients in addition mini (dexa) regimes were administered, BEAM and DHAP resp., with the objective to achieve maximum reduction of the tumourous mass before high-dosage treatment with the support of autologous PBSC. The authors administered 119 cycles of salvage chemotherapy (51 VIM, 46 MINE, 22 mini-dexa-BEAM and DHAP). The toxicity of chemotherapy and the therapeutic response were evaluated according to WHO criteria. The toxicity of VIM and MINE, with the exception for mobilization of desirable transient leukopenia, was not serious. During stimulation of PBSC on average three leukophereses were made and on average 9.9. 10(6) CD34+ cells/kg body weight of the patient were obtained and 53.2. 10(4) CFU-GM/kg (VIM), and 13.5. 10(6) CD34+ cells/kg 53.4. 10(4) CFU-GM/kg (MINE) resp. A total of 64% (MINE) and 61% (VIM) therapeutic responses were obtained, 14% (MINE) and 26% (VIM) complete remissions and 50% (MINE) and 35% (VIM) partial remissions. CONCLUSIONS: Life saving regimes, VIM and MINE, have a good antilymphoma activity, low toxicity and in combination with growth factors (filgrastim) they ensure a good collection of PBSC. As compared with other regimens, in particular for stimulation, VIM and MINE appear to be better.
Adolescent↗
Current role of immunotherapy in multiple myeloma.
Myeloablative chemotherapy improved the results of multiple myeloma treatment but the disease remains incurable. Residual disease eradication is one of the main clues for further improvement of the prognosis of myeloma patients. Interferon alpha maintenance therapy has controversial results. New methods, such as consolidation therapy, antibodies, gene therapy, interleukins, immunotoxins, dendritic cells, vaccines and induction of graft-versus-tumor effect, are tested in the phase I/II clinical trials. This article briefly reviews the new treatment modalities of immunotherapy. Progress in adoptive cellular immunotherapy and progress in induction of graft versus myeloma effect are very promising. We are still not able to transfer very good preclinical results of immunotherapy into clinical results in vivo measured by event free and long-term survivals. Combination of myeloablative therapy followed a new type of immunotherapy focusing on residual disease eradication evaluated in the setting of sensitive disease may be optimal. Such approach could improve the current controversial status of immunotherapy in MM.
Clinical Trials as Topic↗