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W Wilmanns

Publications and source records attributed to W Wilmanns.

At least 19 recordsLinked to original sources
PubMed2001

Local immunotherapy of glioma patients with a combination of 2 bispecific antibody fragments and resting autologous lymphocytes: evidence for in situ t-cell activation and therapeutic efficacy.

After adoptive transfer of pre-activated lymphocytes into the operation cavity of glioma patients, tumor regression and improved survival have been reported in some patients. Results were most impressive when bispecific antibodies with tumor x CD3 specificity were also applied. In this study, we attempted to avoid time-consuming pre-activation procedures for adoptively transferred cells by using a combination of bispecific antibodies directed to the EGF receptor (EGFR) on tumor cells and to CD3 and CD28 on T cells. Eleven patients with high-grade malignant glioma received 3 injections of 2 bispecific antibody fragments (EGFR x CD3 and EGFR x CD28) together with freshly isolated autologous lymphocytes via an Ommaya reservoir. Intracavitary fluid aspirated during immunotherapy was examined for markers of T-cell activation. Increased levels of soluble IL-2 receptor and TNF-alpha were detected in the intracavitary fluid of all patients tested. Two of the 11 treated patients experienced a beneficial response to therapy as defined by a transient contrast enhancement in subsequent MRI scans and prolonged survival. Side effects were transient and consisted of fever, nausea, headache and aggravation of pre-existing neurologic deficits. These adverse effects were most likely due to the antibody construct containing anti-CD3 specificity. Two patients developed cerebral edema and required steroid treatment.

Adult↗
PubMed2000

Modulation of CD95 in leukemia and lymphoma cells by retinoids.

Retinoids are highly active for the treatment of acute promyelocytic leukemia, but have effects on many different types of normal and transformed cells. CD95 is a member of the TNF-receptor superfamily and can mediate apoptosis. In this study, we screened a series of 7 myeloid and 12 lymphoid cell lines for the expression of CD95 and for the induction of CD95 by retinoids. A differential response was observed: in 3/7 myeloid cell lines a significant down-regulation of CD95 happened which correlated with the induction of differentiation. A significant induction of CD95 was observed in 4/ 12 lymphoid lines (2 HHV8+ cell lines, one Burkitt line and another lymphoma line). The modulation of CD95 was both time- and dose- dependent (maximum reached after 3-5 days of culture with 10-6 M retinoid). The 3 retinoid compounds studied (all-trans retinoic acid, 9-cis retinoic acid and 13-cis retinoic acid) had comparable activity. Taken together, we describe a new mode of induction of CD95 in lymphoma cells. More work is needed to define the functional consequences of these changes in CD95 surface expression.

Apoptosis↗
PubMed2000

Prognostic significance of increased IL-10 production in patients prior to allogeneic bone marrow transplantation.

IL-10 is a potent immunosuppressant which inhibits allo-antigen-specific T cell responses. In addition, IL-10 is a strong endogenous anti-inflammatory cytokine. To investigate the role of IL-10 in the induction of acute GVHD following allogeneic bone marrow transplantation (BMT) we performed a prospective study on spontaneous IL-10 production by peripheral blood mononuclear cells (PBMNC) in 84 patients admitted for allogeneic BMT. High spontaneous IL-10 production by PBMNC at the time of admission and prior to any preparative treatment correlated with a subsequent low incidence of GVHD and transplant-related mortality (8%), as compared to patients with low or intermediate IL-10 production (50%, P < 0. 01). Our data demonstrate the prognostic significance of increased IL-10 production in BMT patients and suggest a major role of IL-10 in maintaining immunobalance in the setting of allogeneic BMT. Bone Marrow Transplantation (2000) 25, 237-241.

Adolescent↗
PubMed1999

Tumor-growth inhibition with bispecific antibody fragments in a syngeneic mouse melanoma model: the role of targeted T-cell co-stimulation via CD28.

The ability of bispecific antibodies with anti-tumor x anti-CD3 specificity to mediate the killing of tumor cells by activated T cells has been demonstrated in many in vitro experiments. Moreover, long-term survival of lymphoma-bearing mice has been observed after treatment with such reagents. The therapeutic effect of bispecific antibodies in solid-tumor models has been less impressive, in particular if fragmented antibodies were used to avoid systemic T-cell activation by bispecific constructs binding to Fc-receptor-positive cells. Here we report that bispecific anti-tumor x anti-CD3-fragments markedly inhibit intraperitoneal as well as pulmonary tumor growth in mice inoculated with B16 melanoma cells, resulting in the long-term survival of animals. Therapeutic success critically depends on the number of recruitable effector cells at the site of tumor growth. A second bispecific construct triggering the co-stimulatory CD28-molecule on the T-cell surface increased tumor-cell killing in vitro and in vivo, despite rather low avidity of this reagent to mouse T cells. Finally, long-term-surviving animals showed improved survival after i.v. rechallenge with tumor cells, indicating that bispecific antibodies are capable of inducing long-lasting protective immunity.

Animals↗
PubMed1999

Second malignancies after Hodgkin's disease: the Munich experience.

The occurrence of second malignancies (SM) is an important late event following the treatment of Hodgkin's disease (HD). We sought to determine the incidence, the risk factors, and the prognosis of SM in our population of patients with HD. A total of 1120 patients diagnosed with HD were registered at six participating institutions in Munich (calendar period 1974-1994). The mean follow-up for the development of SM was 9.1 years. A cumulative treatment score was calculated for both radio- and chemotherapy. The relative and absolute risks of SM were established. All SM were investigated for response to treatment and outcome. We observed 85 SM [eight leukemias, 22 non-Hodgkin's lymphomas (NHL), two plasma cell neoplasias, and 53 solid tumors]. Five patients developed third malignancies. The relative risk of developing a second neoplasm was compared with that within the normal population and was 3.1-fold. The risk varied according to the category of SM. Higher relative risks (20.5 and 25.9-fold), but lower absolute risks were observed for leukemias and non-Hodgkin's lymphomas. Solid tumors had lower relative risks (1.8-fold). Splenectomy increased the risk of SM (relative risk 4.4-fold versus 2.7-fold). The risk of SM did not correlate with the initial treatment (radio- or chemotherapy) and did not decrease with prolonged follow-up. The cumulative intensity of radiotherapy, chemotherapy, or the two modalities combined correlated with the risk of SM. Since some cases occurred early after diagnosis, not all second neoplasms can be considered treatment-associated. After 15 years, an actuarial risk of 11.7% was calculated for all SM, of 1.0% for leukemias, of 3.0% for NHL, and of 7.7% for solid tumors. The prognosis of SM varied between good (thyroid cancer, melanoma: median survival 5+ years), average (breast cancer, NHL), and poor (acute myeloid leukemias, lung cancers: median survival 9 months). With the exception of NHL, second cancers often occurred in topographic relation to the field of previous radiotherapy. Taken together, in our patient population, we observed all three categories of SM (solid tumors, leukemias, NHL). The risk for second leukemias is lower than in previous studies, whereas the risk of second NHL is somewhat higher. We confirm that splenectomy is a possible risk factor for SM. Even after correction for the age-specific cancer incidence, treatment intensity is associated with the development of second malignant tumors. Continued follow-up is mandatory after treatment for HD. Since the prognosis of most SM is unfavorable, early recognition and prevention are of the utmost importance.

Adolescent↗
PubMed1999

GM-CSF stimulates proliferation of clonal leukemic bone marrow cells in acute myeloid leukemia (AML) in vitro.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate granulocytes, monocytes, and macrophages. We studied the effect of GM-CSF on (clonal) bone marrow (BM) cells obtained from AML patients after 7 days of culture in vitro: BM samples were obtained from 19 AML patients at diagnosis (DIA), from two patients with persisting disease (PERS), from eight patients in complete remission (CR), and from 12 healthy donors. Flow-cytometric comparison of differentiated, CD 15-positive cells or of CD34-positive blast cells before and after cultivation showed that the proportion of CD15-positive cells was increased in nine of 12 healthy BM samples, in 14 of 19 cases at DIA, in one of three cases during PERS, and in five of six cases in CR of AML. The proportion of CD34-positive cells was increased in one of 12 healthy BM samples, in seven of 19 cases at DIA, in one of two cases during PERS, and in three of seven cases in CR of AML. Southern blot analysis (SBA) performed in six cases during the course of AML, before and after cell culture, showed that clonal DNA increased after GM-CSF treatment in three of five cases studied at DIA, in six of nine cases studied in CR, in the one case studied at PERS, and in the one studied at relapse (REL). In one case of trisomy 8 at DIA a normal karyotype was demonstrated in CR. However, after 7 days of cultivation of the cells in GM-CSF the trisomy 8 was detected in two of 17 metaphases isolated from colony-cells from methylcellulose cultures. Our data show that a 7-day treatment of BM cells with GM-CSF induced a differentiation of healthy and leukemic BM cells in the great majority of cases. An enrichment of CD34-positive cells was not achieved in healthy BM samples. However, in 70% of the cases in CR and in 30% of the cases at DIA of AML, clonal CD34-positive cells were enriched. This means that GM-CSF stimulates ('primes') leukemic cell growth in vitro.

Antigens, CD34↗
PubMed1999

Bcl-2, bax and bcl-xL expression in human sensitive and resistant leukemia cell lines.

With the growing understanding of cytostatic drug-induced programmed cell death new drug-resistance mechanisms based on the altered ability of cells to die by apoptosis have been defined. At first, the sensitive and P-glycoprotein (P-gp)-related resistant cell lines were tested to induce apoptosis by a non-P-gp transported drug, such as cytosine arabinoside (ara-C). It was demonstrated that ara-C induces apoptosis in sensitive as well as in P-gp-related resistant cell lines, as expected. Furthermore, the role of bcl-2 and bcl-xL apoptosis inhibitors as well as bax expression (apoptosis inducer) in human sensitive leukemic cell lines (CCRF-CEM and HL-60) as compared to their resistant variants such as CCRF-CEM/ACT400, CCRF-CEM/VCR1000, HL-60/IDA40, HL-60/DNR250 was evaluated. In addition to the P-gp-related resistance, a possible multidrug resistance-associated protein (MRP) and the lung resistance protein (LRP)-related resistance were assessed by flow cytometry using the monoclonal antibodies 4E3.16, MRPr1 and LRP56. Furthermore, the function of P-gp was determined with the rhodamine-123 (R-123) accumulation test. Bcl-2 and bax were analyzed by both flow cytometry and ECL Western blot, bcl-xL by ECL-Western blot alone. Comparison of the two sensitive cell lines demonstrated different bcl-2, bax and bcl-xL patterns. The common characteristic was the increased expression of one of the apoptosis inhibitor proteins, such as bcl-2 or bcl-xL. The sensitive CCRF-CEM showed a high bax level, where a decrease of about 75% in resistant variants was measured. Compared to their sensitive counterpart HL-60, a low bax expression was analyzed, which increased in the resistant variant. The common characteristic of all resistant cell lines was the decreased expression of bax compared to bcl-2 or bcl-xL. In the P-gp-related resistant HL-60/DNR250 only an increase in bcl-xL was seen, whereas in the LRP-expressing as well as P-gp and MRP negative resistant HL-60/IDA40 both apoptotic inhibitor proteins bcl-2 and bcL-xL showed maximum increase, compared to the other resistant cell lines. The P-gp-related resistant cell lines CCRF-CEM/ACT400 and CCRF-CEM/VCR1000 also showed an increased expression of both bcl-2 and bcl-xL. Summarizing these results, it was shown that the examined sensitive human leukemic cell lines and their resistant variants demonstrated a different pattern of markers for preventing and promoting apoptosis. An association between P-gp and possible LRP-expressing leukemic cells as well as apoptosis-preventing markers (bcl-2, bcl-xL) seems to exist. The clinical relevance of the coexpression of various resistance mechanisms remains to be confirmed in large leukemia patient groups.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

Drug-induced apoptosis in chronic lymphocytic leukemia.

Glucocorticoids and fludarabine are able to induce typical features of apoptosis in CLL lymphocytes. Cysteinyl aspartate specific proteases (caspases) play a key biochemical role in the apoptotic pathway. Caspase activation following cytotoxic stimuli leads to highly specific proteolytic cleavage of functionally important cellular enzymes. One of them is poly ADP-ribose) polymerase (PARP). To some extent caspase activation seems to be under the control of the Bcl-2 family of interacting proteins. We determined the role of Bcl-2-family proteins Bcl-2 (anti-apoptotic) and Bax (pro-apoptotic), activation of caspase-3 (CPP32/Yama) and activation of PARP in CLL apoptosis. All 21 analyzed CLL samples expressed Bcl-2 and Bax. Four of 13 (31%) samples with a low Bcl-2/Bax ratio exhibited in vitro prednisolone resistance, whereas eight of nine (88%) samples with a high Bcl-2/Bax ratio were in vitro resistant (</=0.025). There was no significant correlation between clinical pre-treatment status and Bcl-2/Bax ratio. Caspase-3/CPP32 activity increase was registered after dexamethasone as well as after fludarabine treatment in CLL lymphocytes in vitro. Caspase inhibitor Z-VAD.fmk was only able to partially block dexamethasone-induced and spontaneous apoptosis but not fludarabine-induced apoptosis in CLL lymphocytes. PARP activity decreased after dexamethasone and fludarabine treatment. PARP inhibitor 3-aminobenzamide (3-AB) was able to partially inhibit dexamethasone-induced apoptosis but not fludarabine-induced and spontaneous apoptosis.

Aged↗
PubMed1998

Induction of leukotriene production by bleomycin and asparaginase in mast cells in vitro and in patients in vivo.

Bleomycin and asparaginase are widely used antineoplastic agents which may induce allergic or inflammatory side-effects. Mast cells are implicated as effector cells in allergic and inflammatory responses. The aim of this study was to establish whether bleomycin or asparaginase modulate leukotriene production in vitro and in vivo. Leukotriene C4 (LTC4) production by murine bone marrow-derived mast cells (BMMC) was determined by radioimmunoassay (RIA). Leukotriene production in patients was assessed by determining leukotriene E4 and N-acetyl-leukotriene E4 in urine by means of combined HPLC and RIA. Bleomycin induced an up to 2.1-fold increase in LTC4 production both in unstimulated and in calcium ionophore-stimulated mast cells. In 3 of 7 patients treated with bleomycin, a greater than 2-fold increase in endogenous leukotriene production was observed. This effect was associated with febrile responses and was most pronounced in a patient who developed an Adult Respiratory Distress Syndrome (ARDS). Asparaginase increased leukotriene production up to 10-fold in stimulated but not in unstimulated BMMC. In a patient who developed an anaphylactic reaction after treatment with asparaginase, a pronounced increase in urinary leukotriene concentration was observed. In contrast to bleomycin or asparaginase, a number of other cytostatic agents did not significantly change leukotriene production by BMMC. Our data indicate that some of the inflammatory and allergic side-effects of bleomycin and asparaginase could be mediated by leukotrienes, a possible source of which may be mast cells.

Adult↗
PubMed1998

Development of myeloma and secondary myelodysplastic syndrome from a common clone.

We report the case of a 49-year-old woman who presented with a monoclonally IgG kappa expressing myeloma since October 1989. Four years later, after 24 cycles of Melphalan-containing chemotherapy, bone marrow (BM) cells of the patient cytologically revealed myelodysplastic changes for the first time. Cytogenetic examination of the BM obtained in January 1994 showed two clonally aberrant main lines. Each of them represented one of the hematological neoplastic diseases. The quantitatively major clone (MDS-clone) showed a deletion of the long arm of chromosome 7, typical for secondary myeloid disorders. The other clone (myeloma (MM) clone) was characterized by a reciprocal translocation between the short arm of chromosome 8, band q24, a region known to contain the c-myc gene, and the long arm of chromosome 2, band p12, where the Ig kappa gene is located. An unusual finding, however, was that an abnormality of the long arm of chromosome 16 could be detected in both obviously unrelated clones. In the further course of the disease, the MDS and MM clones could be detected, both of them showing cytogenetically a clonal evolution characterized by additional clonal abnormalities. Our data stress the significance of cytogenetics in detecting typical clonal abnormalities in different malignant hematological disorders and in detecting "clonal evolution" as an indicator of the progress of the disease. Moreover, our data suggest that MM and MDS may arise from a common stem cell, which may be characterized by a clonal cytogenetic abnormality.

Chromosome Aberrations↗
PubMed1998

Non-invasive temperature mapping using MRI: comparison of two methods based on chemical shift and T1-relaxation.

PURPOSE: To implement and evaluate the accuracy of non-invasive temperature mapping using MRI methods based on the chemical shift (CS) and T1 relaxation in media of various heterogeneity during focal (laser) and external thermal energy deposition. MATERIALS AND METHODS: All measurements were performed on a 1.5 T superconducting clinical scanner using the temperature dependence of the water proton chemical shift and the T1 relaxation time. Homogeneous gel and heterogeneous muscle phantoms were heated focally with a fiberoptic laser probe and externally of varying degree ex vivo by water circulating in a temperature range of 20-50 degrees C. Magnetic resonance imaging data were compared to simultaneously recorded fiberoptic temperature readings. RESULTS: Both methods provided accurate results in homogeneous media (turkey) with better accuracy for the chemical shift method (CS:+/-1.5 degrees C, T1:+/-2.0 degrees C). In gel, the accuracy with the CS method was +/-0.6 degrees C. The accuracy decreased in heterogeneous media containing fat (T1:+/-3.5 degrees C, CS: +5 degrees C). In focal heating of turkey muscle, the accuracy was within 1.5 degrees C with the T1 method. CONCLUSION: Temperature monitoring with the chemical shift provides better results in homogeneous media containing no fat. In fat tissue, the temperature calculation proved to be difficult.

Animals↗
PubMed1998

Release of prostaglandin D2 by murine mast cells: importance of metabolite formation for antiproliferative activity.

Prostaglandin (PG) D2, PGJ2 and delta12-PGJ2 are antiproliferative eicosanoids. We investigated the production of PGD2 by murine bone marrow-derived mast cells (BMMC) taking into consideration metabolism of PGD2 to PGD2 and delta12-PGJ2. PG-metabolites were quantified by high performance liquid chromatography (HPLC) combined with radioimmunoassay (RIA). Stimulated with calcium ionophore A23187 BMMC released eight-fold more PGJ2 and delta12-PGJ2 than PGD2. Conversion of endogenously produced PGD2 to PGJ2 and delta12-PGJ2 proceeded rapidly in contrast to metabolism of exogenously added PGD2. The antiproliferative potency of these prostaglandins is demonstrated in vitro. We conclude that determination of PGD2 production by mast cells must take into consideration rapid conversion to active derivatives, which may play a significant role in growth regulation.

Animals↗
PubMed1998

In vitro efficacy of known P-glycoprotein modulators compared to droloxifene E and Z: studies on a human T-cell leukemia cell line and their resistant variants.

P-glycoprotein(P-gp)- related resistance is one of the major obstacles in treating leukemia patients. Therefore, it is of clinical interest to find new potential modulators and compare their P-gp-modulating efficacy. The present analysis investigated the influence of P-gp modulators, such as verapamil, tamoxifen, droloxifene E, droloxifene Z, SDZ PSC 833 (PSC 833) and dexniguldipine in a leukemic T-cell line (CCRF-CEM) and its P-gp-resistant counterparts (CCRF-CEM/ACT400 and CCRF-CEM/VCR1000). P-gp expression was assessed with an immunocytological technique using the monoclonal antibody 4E3.16. It was characterized as the percentage of P-gp positive cells and also expressed as a D value by using the Kolmogorov Smirnov statistic. The efficacy of P-gp modulators was determined with the rhodamine-123 accumulation test and the MTT test. An in vitro modulator concentration between 0.1 microM and 3 microM was determined, where no genuine antiproliferative effect was apparent. The modulators PSC 833 and dexniguldipine were the significant (p<C0.05) most potent chemosensitizers followed by verapamil, droloxifene Z, tamoxifen and droloxifene E in descending order. In addition to the modulators PSC 833 and dexniguldipine, droloxifene Z should especially be considered as a candidate for future ex vivo and in vivo studies. The main advantage of droloxifene Z could be the low rate of expected side effects. This fact permits the use of high Drol Z dosage in order to achieve a relevant modulating effect in vivo and to use this drug in combination with a further modulator so as to reach maximum efficacy with tolerable side effects.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Cloning and characterization of bone marrow cells from patients with acute lymphoid leukemia (ALL) in agar cultures.

UNLABELLED: Acute lymphoid leukemias (ALL) represent malignant clonal expansions of lymphoid hemopoietic cells arrested at different stages of B- or T-cell maturation. We studied surface marker profiles and cloning capability of bone marrow (BM) cells from 22 adult ALL-patients at diagnosis (n = 15) or relapse (n = 7) in agar cultures under different culture conditions in order to develop a screening system for the classification of ALL and the detection of residual leukemia. Immunophenotyping of those 22 BM-samples enabled a classification in B- or T-linear ALL. Colony growth of BM-cells could be obtained in four out of 20 cases of ALL at diagnosis and in one case at relapse. Different stimulating factors and their combinations (GM-CSF; IL-1; IL-2; IL-3; IL-4; IL-6; placenta conditioned media (PCM); Phytohemagglutinin (PHA, 40%) and lipopolisaccaride (LPS, 1.25%)--containing conditioned media ('B-ly'); IL-1+IL-3; IL-1+IL-4; IL-1+IL-6; IL-1+B-ly) did not show an overall significant difference in stimulating ALL-clones. Immunological phenotyping of ALL-clones in these 5 cases could prove the lymphoid leukemic character of the clones obtained. CONCLUSIONS: Our data show that colony growth of ALL-BM-cells is difficult. Nevertheless, in cases where colony growth could be obtained those clones showed the original surface marker profile of the leukemic cells proving the specificity of our colony assay.

Acute Disease↗
PubMed1997

Effects of progesterone and leukotriene receptor antagonists in experimental models of P-glycoprotein-related resistance.

P-glycoprotein (P-gp)-related resistance is one of the most intensively investigated mechanisms of multidrug resistance, but the search for better modulators and better modulator combinations has just begun. The present work was performed to determine whether leukotriene LTD4 /LTE4 receptor antagonists such as FPL-55712, Ly-163443, Ly-171883, MK-571 and the progesterone receptor antagonist RU-38486 are potential P-gp modulators in models of P-gp-related resistance. Additionally, the P-gp modulating potency of the combination of RU-38486 and verapamil was investigated. P-gp expression was determined with the monoclonal antibody 4E3.16, and functional activity was assessed by the Rhodamine123 (R123) accumulation assay. Efficacy of the modulators was determined with the MTT test and the R123 accumulation assay. The in vitro examinations were done in the P-gp-resistant human T-lymphoblastic cell lines CCRF-CEM/ ACT400 and CCRF-CEM/VCR1000. No P-gp-modulating effect was observed with Ly-163443, Ly-171883, FPL-55712 or MK-571. A significant (p<0.05) cytotoxicity of the examined modulators per se (without actinomycin D or vincristine) was demonstrated only for verapamil at a concentration of 10 microM. At a concentration of 10 microM a significant (p<0.05) P-gp modulating effect was observed with RU-38486, which was even more pronounced than the effect of verapamil as determined by the MTT test. Using the R123 accumulation assay it was shown that the combination of RU-38486 (6 microM and 10 microM) and verapamil additively increased (p<0.05) the percentage of accumulating cells. This additive effect was reflected by a significantly (p<0.05) enhanced efficacy of the combination of drugs with respect to inhibition of cell proliferation. The data presented advocate testing of new potential P-gp modulator combinations, such as RU-38486 and verapamil, with the aim of increasing efficacy and simultaneously reducing side effects.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Subclassification of diffuse large B-cell lymphomas according to the Kiel classification: distinction of centroblastic and immunoblastic lymphomas is a significant prognostic risk factor.

Among high-grade malignant non-Hodgkin's lymphomas the updated Kiel classification identifies three major B-cell entities: centroblastic (CB), B-immunoblastic (B-IB), and B-large cell anaplastic (Ki-1+) (now termed anaplastic large cell [CD30+], [B-ALC]). The clinical prognostic relevance of this distinction was evaluated in a randomized prospective treatment trial (COP-BLAM/IMVP-16 regimen randomly combined +/- radiotherapy in complete responders) conducted in adult (age 15 to 75) patients with Ann Arbor stage II-IV disease (n = 219) diagnosed by optimal histomorphology (Giemsa staining) and by immunohistochemistry. Overall survival was significantly better in CB lymphoma as compared to B-IB (P = .0002) or B-ALC (P = .046). Relapse-free survival was worse for B-IB (P = .0003) as compared to CB lymphomas. The prognostic differences between CB and B-IB were confirmed by multivariate analyses including the risk factors of the International Index. Overall survival was significantly determined by performance status (P = .0003), serum-LDH (P = .036), and B-IB histology subtype (P = .036). Relapse-free survival was influenced by age (P = .007) and histological subtype (P = .007). Thus, the diagnosis of the CB and B-IB lymphomas by the histological criteria of the Kiel classification was identified as an independent prognostic factor in diffuse large B-cell lymphomas.

Adolescent↗