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Biomedical subjects

W Knauf

Publications and source records attributed to W Knauf.

At least 19 recordsLinked to original sources
PubMed2004

Modern diagnostics in chronic myeloproliferative diseases (CMPDs).

According to the new WHO classification a group of chronic myeloproliferative diseases (CMPDs) were defined: chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia and hypereosinophilic syndrome (CEL/HES), polycythemia vera (PV), chronic idiopathic myelofibrosis (with extramedullary hematopoiesis, CIMF), essential thrombocythemia (ET), and so called CMPD/unclassifiable. As clinical features and laboratory findings differ widely between these diseases several diagnostic approaches are mandatory at diagnosis for classification and are needed also for follow up studies, especially for the measurement of minimal residual disease (MRD). We here outline the laboratory set up at diagnosis and during follow up in CMPDs with specific focus on the respective therapeutical consequences. Only by using a comprehensive diagnostic panel including cytomorphology, cytogenetics, and molecular genetic methods establishing the correct diagnosis, optimizing treatment as well as evaluating treatment response is possible in CMPDs today.

Blood Cell Count↗
PubMed2004

Efficacy and tolerability of alemtuzumab (CAMPATH-1H) in the salvage treatment of B-cell chronic lymphocytic leukemia--change of regimen needed?

We report on the response rate and tolerability of Alemtuzumab (Campath-1H) in a series of heavily pretreated patients with B-CLL with a special focus on treatment-related problems. All patients tested positive for CD52 on B-lymphocytes before entering the trial. Thirteen patients with B-chronic lymphocytic leukemia (B-CLL), 1 prolymphocytic leukemia (PLL), 1 mantle cell lymphoma (MCL) and 1 leukemic immunocytoma (IC) transformed into a high-grade NHL were included. Median age was 62 years (range 40-73), and pretreatment consisted of median 3 prior regimens (range 1-11). All patients received 3, 10 and 30 mg of Campath-1H on sequential days, and then were subsequently scheduled for 30 mg 3 times weekly. Nine out of 16 patients responded. One patient attained complete remission (CR), 8 patients achieved partial remission (PR), while 4 patients had stable disease (SD). Three patients had progressive disease (PD). Beginning with initiation of treatment recurrent profound leukopenia became evident in 13 out of 16 patients leading to treatment discontinuation. Severe nonhematological toxicity (WHO grade IV bronchospasm) occurred in the first patient of this series, who initially had no concomitant steroids. Therefore, we developed a steroid co-medication regimen for the first 4 Campath-1H applications with quick tapering thereafter. Following this regimen, no infusion associated side effects WHO grade > II were observed. Infectious complications leading to treatment discontinuation consisted of pulmonary aspergillosis in one and bacterial pneumonia in another case. One patient with refractory B-CLL and Pneumocystis carinii pneumonia plus CMV reactivation died. In summary, Campath-1H appears to be effective against leukemic low-grade B-NHL, also in advanced stage. In our series, application 3 times weekly was not possible due to hematotoxicity. We recommend, therefore, flexible time intervals depending on the leukocyte counts. Whether a cumulative dosage according to 3 x 30 mg Campath-1H for 12 weeks is needed still remains to be clarified.

Adult↗
PubMed2004

Endurance exercise and the production of growth hormone and haematopoietic factors in patients with anaemia.

BACKGROUND: Physical activity has been shown to stimulate haematopoiesis in patients with anaemia due to chronic renal failure or haematological malignancies. OBJECTIVE: To evaluate the effect of moderate exercise on the production of haematopoietically active factors. METHODS: Ten patients (four men and six women, mean (SD) age 51 (10) years) with a haemoglobin concentration under 130 g/l (men) or 120 g/l (women) carried out five three minute exercise bouts at an intensity of 80% of the maximal heart rate, corresponding to a lactate concentration of 3 (0.5) mmol/l. Patients rested for three minutes between bouts. The concentrations of interleukin 6, stem cell factor, granulocyte-monocyte colony stimulating factor, granulocyte colony stimulating factor, erythropoietin, and growth hormone (GH) were evaluated before and in the eight hours after exercise. RESULTS: GH had risen significantly 15 minutes after exercise (1.1 (1.3) v 2.7 (2.8) ng/ml; p<0.05). No change in the concentration of the other cytokines and growth factors was observed in the eight hours after exercise. CONCLUSIONS: In patients with anaemia, submaximal exercise does not affect the concentration of haematopoietically active cytokines. However, it leads to an increased concentration of GH. This may be responsible for the improved haematopoiesis observed after an exercise programme in patients with chronic diseases.

Adolescent↗
PubMed2002

Filgrastim mobilization and collection of allogeneic blood progenitor cells from adult family donors: first interim report of a prospective German multicenter study.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilized peripheral blood progenitor cells (PBPCs) from healthy individuals are a rapidly emerging alternative source to bone marrow for allogeneic transplantation. Although widely applied in the meantime, only limited information on feasibility and safety of mobilization and collection of PBPCs is currently available from prospective multicenter studies specifically designed to investigate this donation modality. This ongoing multicenter study on the performance as well as the short- and long-term safety profile of rhG-CSF-induced mobilization and collection of PBPCs was initiated in October 1999. The study is designed to recruit a total of 300 healthy family donors who will be followed regularly for a period of 5 years after donation. The first interim report presented here summarizes results obtained after enrollment of 150 donors from nine German institutions. The study protocol allowed the individual choice between two dose regimens of rh-CSF (10 micro g/kg per day vs 2x8 micro g/kg per day of donor body weight). The primary endpoint was defined as a yield of > or =5x10(6) CD34(+) cells/kg of recipient body weight in a single leukapheresis product. This endpoint was attained by 50% of donors receiving the lower rhG-CSF dose regimen and by 75% of donors with the higher dose regimen ( p<0.0009). A total of 478 acute adverse events attributable to the mobilization procedure were recorded and manifested predominantly as transient bone pain and headaches (80%). No persistent hematologic or nonhematologic adverse events have occurred in this study so far. Thus, the current experience in a prospective multicenter study supports previous single-center and retrospective registry reports in that the collection of PBPCs after rhG-CSF mobilization is feasible and associated with frequent, but generally mild and acceptable side effects.

Adolescent↗
PubMed2002

Quantitative real-time RT-PCR detects elevated Wilms tumor gene (WT1) expression in autologous blood stem cell preparations (PBSCs) from acute myeloid leukemia (AML) patients indicating contamination with leukemic blasts.

High-dose chemotherapy with subsequent autologous stem cell transplantation is believed to be of therapeutic benefit in patients with acute myeloid leukemia (AML), especially when no allogeneic bone marrow donor is available. One of the main risks is contamination of the stem cell preparations with leukemic blasts, which may account for a higher relapse rate compared to allogeneic bone marrow transplantation. Since overexpression of WT1 is common in leukemic blasts, we investigated, whether PBSCs from AML patients express WT1 at a higher level as compared to patients with solid cancers. PBSCs of seven patients with AML and of five patients with solid cancers were investigated for WT1 expression. Total WT1 copy count was determined in a standardized quantitative real time RT-PCR. WT1 expression was found in all AML PBSCs with an average copy number of 49.99 +/- 61.09. In solid cancers WT1 expression was statistically significantly lower with a copy number of 3.51 +/- 1.92. In AML patients with sustained complete remission we found a nearly significantly lower WT1 expression than in patients who relapsed within the first year after stem cell transplantation. Our data show a higher WT1 expression in PBSCs of AML patients compared to patients with solid cancers. This finding might indicate a contamination with leukemic blasts. Quantification of WT1 in PBSCs might therefore be useful to estimate the risk of relapse after autologous stem cell transplantation in AML patients.

Acute Disease↗
PubMed2002

Nonmyeloablative stem cell transplantation in adults with high-risk ALL may be effective in early but not in advanced disease.

The feasibility of nonmyeloablative stem cell transplantation (NST) was evaluated in 22 adults with high-risk ALL. 16/22 patients had advanced disease and 11/22 had Ph+ ALL. Eleven patients received NST as first stem cell transplantation (SCT). Eleven patients had relapses after allogeneic or autologous SCT and underwent a salvage NST. 18/22 patients (82%) engrafted after NST. 13/16 patients (81%) with active disease reached complete remission (CR). 11 of 13 patients developed GVHD. After first NST 10/11 patients (91%) engrafted. Six of seven patients with active disease reached CR. Three of five relapsing patients reached subsequent CR after donor lymphocyte infusions, termination of immunosuppression or imatinib. Three of 11 patients (27%) are alive in CR 5 to 30 months after NST. Eight of 11 patients have died, 3/8 from leukemia and 5/8 from transplant-related causes. After salvage NST, 8/11 patients (73%) engrafted. Seven of nine patients with active disease reached CR. Only one of 11 patients transplanted, who was in CR before undergoing salvage NST is alive 19 months after NST. Five of 11 have died from leukemia, one of 11 after graft failure and four of 11 from transplant-related causes. Four of 22 patients (18%) are alive in CR 5, 14, 19 and 30 months after NST. NST is feasible in adults with high risk ALL. However, transplant-related mortality remains high and only patients transplanted in CR seem to have long-term disease-free survival.

Adult↗
PubMed2002

Dual effects of arsenic trioxide (As2O3) on non-acute promyelocytic leukaemia myeloid cell lines: induction of apoptosis and inhibition of proliferation.

Clinical efficacy of As2O3 has been shown in patients with relapsed acute promyelocytic leukaemia (APL). There is evidence that the effects of As2O3 are not restricted to events specific for APL. As2O3 might target mechanisms involved in the pathogenesis of other malignancies. We assessed susceptibility to induction of apoptosis by As2O3 and cytostatics in 22 myeloid and non-myeloid malignant cell lines. As2O3 was used in concentrations of 0.01-10 micromol/l. Cell lines displayed different kinetics of response and different sensitivity to As2O3. The minimum concentration of As2O3 for induction of apoptosis was 0.1 micromol/l. High concentrations of As2O3 (5 micromol/l) induced apoptosis in a large proportion of cells in all cell lines tested. Low (1 micromol/l As2O3) concentrations induced apoptosis in NB-4, HL-60, U-937, CEM, HL-60, KG-1a, PBL-985, ML-2 and MV-4-11, but not in HEL, K-562, KG-1 and Jurkat up to 35 d of incubation. However, the non-apoptotic population of 1 micromol/l As2O3-treated HEL, K-562, K-562 (0.02), K-562(0.1) and Jurkat showed reduced proliferation. CEM as well as its' multidrug-resistant derivatives were sensitive to 1 micromol/l As2O3. In summary, these data demonstrate that As2O3-induced apoptosis is not restricted to cell lines with t(15;17). Apoptosis was induced in vitro by As2O3 concentrations that are achievable in vivo after infusion of well-tolerated As2O3 doses. Thus, As2O3 might be a suitable therapeutic agent for malignancies other than APL provided the adequate dose and duration of As2O3 treatment are used.

Antineoplastic Agents↗
PubMed2001

Rituximab therapy of patients with B-cell chronic lymphocytic leukemia.

Rituximab (IDEC-C2B8) is a chimeric antibody that binds to the B-cell surface antigen CD20. Rituximab has significant activity in follicular non-Hodgkin lymphomas. Much less is known about the effects in chronic lymphocytic leukemia (CLL). We have initiated a phase II trial to evaluate the efficacy and safety of rituximab in patients with CD20+ pretreated CLL. To avoid the rituximab-associated toxicity, we restricted the tumor cell load, as measured by the number of circulating lymphocytes and the spleen size, in the first 2 cohorts of patients included in the study. Patients received 4 intravenous infusions of 375 mg/m2 once a week over a period of 1 month. Of the 28 patients evaluable for response, 7 patients showed a partial remission (National Cancer Institute criteria) lasting for a median of 20 weeks, with 1 patient still in remission after 71 weeks. Based on lymphocyte counts only, we found at least a 50% reduction of lymphocyte counts lasting for at least 4 weeks in 13 (45%) of 29 patients. Fifteen patients from 3 institutions were monitored for the immunophenotype profile of lymphocyte subsets. The number of CD5+CD20+ cells decreased significantly and remained low until day 28 after therapy. T-cell counts were not affected. With the exception of one rituximab-related death, adverse events in the remaining patients were mild. The results suggest that rituximab has clinical activity in pretreated patients with B-CLL. Toxicity is tolerable. Response duration after withdrawal of rituximab is rather short. Therefore, other modes of application and the combination with other agents need to be tested.

Adolescent↗
PubMed2001

Cyclophosphamide, adriamycin and dexamethasone (CAD) is a highly effective therapy for patients with advanced multiple myeloma.

BACKGROUND: Patients with advanced multiple myeloma (stage III or progressive myeloma) received the CAD protocol every three weeks: cyclophosphamide 200 mg/m2 i.v./orally days 1-4, adriamycin 30 mg/m2 i.v. on day 1 and dexamethasone 40 mg p.o. days 1-4. PATIENTS AND METHODS: Forty-six patients with a median age of sixty years (range 34-84 years) were enrolled. According to Durie-Salmon 44 patients were in stage III, 2 in stage II; 6 patients had renal insufficiency (stage B). Twenty-three patients were pre-treated at least with melphalane/prednisone. RESULTS: Remission rates were as follows: complete remission 4%, partial remission 70%, minimal change 11%, no change 11%, progressive disease 4%. After an observation time of 14 months the median progression free interval for 33 patients not treated with subsequent high-dose chemotherapy with stem-cell support was more than 14 months. Overall, treatment was well tolerated. After 209 cycles given febrile neutropenia occurred in 11% of cycles including one fatal outcome. Neutropenia or thrombocytopenia grade 3-4 WHO was recorded in 18% and 6% of the cycles, respectively. CONCLUSIONS: This study shows that CAD is an effective regimen with an overall remission rate of 74%. The CAD protocol should be further evaluated in prospective trials.

Administration, Oral↗
PubMed2001

Fludarabine plus cyclophosphamide is an efficient treatment for advanced chronic lymphocytic leukaemia (CLL): results of a phase II study of the German CLL Study Group.

The efficacy and toxicity of a combination of fludarabine and cyclophosphamide (FC) was evaluated in patients with B-cell chronic lymphocytic leukaemia (CLL). Between April 1997 and July 1998, 36 patients with CLL (median age 59 years) received a regimen that consisted of fludarabine 30 mg/m(2) in a 30-min IV infusion, d 1-3, and cyclophosphamide 250 mg/m(2) in a 30-min IV infusion on d 1-3. Cycles were repeated every 28 d. Twenty-one patients had received between one and three different treatment regimens prior to the study, while 15 patients had received no prior therapy. The median Eastern Cooperative Oncology Group performance score was 1. One patient was at Binet stage A, 18 were stage B and 17 patients were stage C. Objective responses, assessed according to the revised guidelines of the National Cancer Institute-sponsored Working Group, were recorded in 29 out of 32 assessable patients (90.6%). Twenty-four partial remissions and five complete remissions were observed. Two patients showed no change and one patient showed disease progression. At February 2000, three of the responders had relapsed. Severe neutropenia, anaemia and thrombocytopenia (Common Toxicity Criteria grade 3 and 4) were observed in 25, six and six patients (69.4%, 16.7% and 16.7%) respectively. Other side-effects were uncommon. No treatment-related deaths and no grade 3 or 4 infections occurred. We conclude that the combination of fludarabine and cyclophosphamide showed significant activity in patients with CLL. Myelosuppression was the major side-effect. These results warrant further study on the FC combination in randomized trials.

Adult↗
PubMed2001

Analysis of chimerism during the early period after allogeneic peripheral stem cell transplantation.

As there are few reports on early evaluation of chimerism, we assessed fluorescence short tandem repeats (STR) by polymerase chain reaction (PCR) assays to analyse donor and recipient characteristics at early time points after peripheral stem cell transplantation (PBSCT). Peripheral blood of 13 patients was analysed in 1- to 2-day intervals starting from the day of PBSCT. Donor and recipient allelic patterns were determined by a commercially available multiplex STR assay that simultaneously evaluates four or five gene loci. Mixed chimerism appeared in all patients during days 1-9 after transplantation and preceded haematologic engraftment for 3-12 days. Even patients without myeloablative conditioning therapy (n=4) revealed donor allelic patterns within 1-5 days. Nine patients changed during the following days to a complete donor allelic pattern and had an uncomplicated post-transplant disease course. Four patients did not consistently retain complete donor chimerism; two of them relapsed within the next 3 months, one died from septicemia within 7 days, and the fourth, transplanted for aplastic anaemia, is still in complete remission. Overall, STR analysis using a simple and comparatively cheap multiplex system permits the detection of chimerism very early after transplantation and may provide relevant information that correlates with the clinical follow-up.

Adult↗
PubMed2001

MDR-1 expression and deletions of chromosomes 7 and 5(Q) separately indicate adverse prognosis in AML.

In order to assess any correlation between MDR-1 expression and chromosomal aberrations, and to define their impact on clinical outcome in newly diagnosed AML pts, we investigated bone marrow and peripheral blood samples of 49 consecutive pts admitted to our hospital. Monosomy 7, trisomy 8 and 5q- were evaluated by means of interphase fluorescence in situ hybridization (FISH). Monosomy 7 was present in 6 pts, trisomy 8 in 5 pts, and 5q- in 6 pts. More than one aberration was seen in 7 pts. Chromosomal aberrations were mostly found in older pts (12/14 >60 years; p=0.03) and in pts with CD34 positive leukemic blasts (13/14 coexpressed CD34, p=0.0004). In 25 pts also standard G-banding analysis was performed leading to concordant results regarding chromosomes 7, 8 and 5. Flow cytometry identifyed MDR-1 positivity (MDR+) in 16 pts. MDR-1 expression appeared to be a characteristic feature in CD34+ AML (12/16 were CD34+ and MDR+ pts; p=0.013). No correlation, however, was found between chromosomal aberrations and MDR-1 expression. Pts with aberrations of either chromosomes 7, 8 or 5 detected by FISH (FISH+) were predominantly resistant to induction therapy (6/8 pts, p=0.004). A lower rate of complete remission (CR) was also seen in pts with MDR-1 expression (p=0.006). MDR+/FISH+ pts (n=3) were all refractory to remission induction, while all MDR-/FISH- pts (n=19) achieved CR (p=0.0006). MDR-1+ as well as pts with aberrations of chromosomes 7, and 5(q) showed a significantly decreased probability of overall survival. In conclusion, MDR-1 expression as well as abnormalities of chromosomes 7, and 5(q) predict poor clinical outcome in AML. The identification of these prognostic factors provides useful information for risk adapted treatment strategies.

Adult↗
PubMed2000

CD34 selected alloPBSCT and adoptive immunotherapy.

To circumvent aGVHD in the early phase after allogeneic stem cell transplantation but to provide GVL activity later on, we performed alloPBSCT with CD34+ selected grafts followed by delayed add-back of CD3+ T cells. Ten consecutive patients having an HLA-identical sibling donor were enrolled on to this trial. Four patients were in first CR of high-risk ALL, another four in first CR of AML, one was in second myeloid blast crisis of CML, and one was in PR of relapsed NHL. Conditioning consisted of 2 x 60 mg/kg CY plus 12 Gy TBI. G-CSF (Filgrastim) mobilized peripheral cells were CD34+ selected using the Isolex 300i system in nine patients and the CliniMacs system in one. Median CD34+ purity was 86%. A median of 2.8 x 10(6)/kg CD34+ cells were transplanted. The number of CD3+ cells in the allografts was 5.7 x 10(4)/kg (median) after Isolex 300i, and 0.2 x 10(4)/kg after CliniMacs. All patients received G-CSF (Filgrastim) and engrafted rapidly. Standard-dose CsA was administered, and until day +60 no aGVHD occurred. At that time point, seven patients received 2 x 10(6)/kg CD3+ cells while CsA had been tapered to 50% of the starting dose. One of these patients died after a second T cell boost given on day +90 without concomitant immunosuppression due to grade IV intestinal aGVHD. Three others developed cutaneous cGVHD. Taken together, T cell depletion by CD34+ selection does not impair rapid engraftment in the HLA-identical sibling donor setting. Using standard-dose CsA the risk for acute GVHD seems to be minimized. Add-back of 2 x 10(6)/kg CD3+ cells on day +60 with CsA protection is feasible. However, whether this is the optimal time point and number of T cells remain to be further elucidated.

Adult↗
PubMed1999

Elevated serum thymidine kinase levels identify a subgroup at high risk of disease progression in early, nonsmoldering chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) shows a remarkably heterogeneous clinical outcome; survival ranges from several months in advanced stages to more than 10 years in early stages. The Binet and Rai staging systems distinguish three major prognostic subgroups, but do not accurately predict the individual risk of disease progression in early CLL (Binet stage A or Rai stage 0 to II). Because most newly diagnosed CLL patients present with early disease, it seems desirable to search for additional prognostic factors to identify early CLL patients at high risk of rapid progression. It has been shown that elevated serum thymidine kinase (s-TK) levels predict disease progression in CLL. Therefore, this study aimed to assess the prognostic value of s-TK in 122 previously untreated patients with Binet stage A CLL (mean age +/- SD, 58.7 +/- 8.5 years). In univariate analyses, 18 of the 22 parameters investigated predicted progression-free survival (PFS). In a stepwise multiple regression analysis, only three parameters provided independent prognostic information on PFS: s-TK greater than 7.1 U/L; presence of lymphadenopathy; and white blood cell (WBC) count greater than 75, 000/microL. When added to the classification of smoldering versus nonsmoldering CLL, s-TK levels separated two groups within the group of nonsmoldering stage A patients: patients with s-TK values greater than 7.1 U/L had a median PFS of 8 months, whereas patients with s-TK values </= 7.1 U/L expected a much longer PFS (49 months; P <. 001), similar to smoldering CLL (42 months). The results demonstrate that s-TK is a prognostic parameter that adds independent prognostic information to the definitions of smoldering and nonsmoldering CLL in Binet stage A.

Adult↗
PubMed1999

CD82 (KAI1), a member of the tetraspan family, is expressed on early haemopoietic progenitor cells and up-regulated in distinct human leukaemias.

CD82 (KAI1) is a member of the tetraspan transmembrane protein family which has been cloned from lymphoblastoid variant cell lines. However, a role for CD82 in early normal and malignant haemopoiesis has not yet been characterized. We studied the CD82 expression in 33 normal donor samples and 98 leukaemias by fluorescence activated cell sorting (FACS) and reverse transcriptase polymerase chain reaction (RT-PCR). We demonstrated that CD82 was moderately expressed in the vast majority of normal granulocytes and monocytes. In contrast, only about one third of the peripheral blood lymphocytes were weakly CD82 positive (CD82+). Interestingly, judgement of the CD82 transcription and expression in various leukaemias revealed that CD82 was overexpressed in chronic myeloid leukaemia (CML) patients in accelerated or blastic phase (CML-AP/BP) as well as in acute myeloid leukaemia (AML) and chronic lymphocytic leukaemia (CLL) patients. Analysis of AML patients with CD34+/CD82+ blasts prompted us to expand our studies on haemopoietic CD34+ progenitor cells. Intriguingly, 84-95% of the CD34+ cells isolated from healthy bone marrow, cord blood or peripheral blood were highly CD82+. CD82 was abundantly expressed on primitive as well as on committed haemopoietic progenitor cells. After in vitro induction of myeloid differentiation in CD34+ peripheral blood progenitor cells (PBPC), the expression of CD82 decreased to levels similar to those found on peripheral blood granulocytes. These observations suggest for the first time a role for CD82 in normal and malignant haemopoiesis.

Antigens, CD↗
PubMed1998

Overexpanded B cell clone mediating leukemic arthritis by abundant secretion of interleukin-1beta: a case report.

The role of cytokines in leukemic arthritis is unknown. The presentation of a patient with B cell chronic lymphocytic leukemia and destructive arthritis of the wrist joints prompted us to study the synovial cytokine pattern by immunohistologic analysis. In addition, rearranged V(H) and V(L) immunoglobulin genes were sequenced to assess B cell clonality. Heavy infiltrations of CD20+ cells with lambda light chain restriction were found in the synovial tissue. Sequencing demonstrated overexpansion of a single B cell clone (DP58/D/J(H)4b and IGLV3S2/Jlambda2-Jlambda3 for V(H) and V(L), respectively) in the peripheral blood. Identical V(H) and V(L) rearrangements were found in the synovial infiltrates. Somatic mutations were found in both the peripheral blood and the synovial clone. Immunohistologic study revealed the presence of abundant interleukin-1beta (IL-1beta) and, to a lesser degree, tumor necrosis factor beta (TNFbeta) (lymphotoxin). In contrast, TNFalpha, interferon-gamma, IL-4, IL-6, and IL-10 were rarely found in the synovial infiltrates. Therefore, IL-1beta secreted in great amounts by leukemic B cells appears to be the major cytokine that mediates joint destruction in leukemic arthritis.

Amino Acid Sequence↗