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Biomedical subjects

C Lindemalm

Publications and source records attributed to C Lindemalm.

At least 19 recordsLinked to original sources

Support group for cancer patients. Does it improve their physical and psychological wellbeing? A pilot study.

In order to evaluate a structured support intervention programme, symptoms and quality of life (QOL) were studied in 61 consecutive cancer patients with different tumour diagnoses in relation to intervention and follow-up. The majority of the patients were female. The Edmonton symptom assessment scale (ESAS), the Norwegian fatigue questionnaire and the hospital anxiety and depression scale (HADS) were used. Data were analysed according to ANOVA and Tukey's honest significant difference (HSD) test. ESAS sickness score (P=0.0001), depression (P=0.0001), anxiety (P=0.0001) and QOL (P=0.0009) improved and the improvements in depression and anxiety were still significant after 3 months (P=0.02 respectively). Aspects of fatigue also improved significantly in 7 of 11 questions after the intervention (P< or =0.04) but these improvements were not observed after 3 months. Anxiety according to the HADS questionnaire improved significantly after the intervention (P=0.0006). The majority of the patients highly appreciated the possibility of sharing thoughts and troubles with others with similar experiences (59%). The programme was therefore found to improve QOL, and physical and psychological functions. Randomized studies in relation to immunological changes and follow-up are in progress.

Adaptation, Psychological↗

Effect of monoclonal antibody 17-1A and GM-CSF in patients with advanced colorectal carcinoma--long-lasting, complete remissions can be induced.

Antibody-dependent cellular cytotoxicity (ADCC) is considered to be one of the effector functions of unconjugated monoclonal antibodies (MAbs) in tumor therapy. The antitumor activity of MAbs might therefore be augmented if the cytotoxic capability of the effector cells could be increased. In an in vitro system, the killing capacity of MAb was significantly enhanced by pre-treatment of the effector cells with granulocyte-macrophage colony-stimulating factor (GM-CSF). Based on these findings, the therapeutic effect of the combination of mouse MAb 17-1A (IgG2a) and GM-CSF was evaluated in 20 patients with metastatic colorectal carcinoma (CRC). The patients received GM-CSF for 10 days and a single i.v. infusion of MAb 17-1A on day 3 of the cycle. Four cycles were given at 1-monthly intervals. There was a continuous increase in blood monocytes and lymphocytes during all 4 GM-CSF cycles. Neutrophils and eosinophils were also significantly augmented but in a biphasic manner and the cell counts on day 10 of cycle IV were significantly lower than in cycles I and II. GM-CSF-related side-effects were of no major clinical importance. During the third cycle, an immediate-type allergic reaction (ITAR) against MAb 17-1A occurred in most patients, necessitating reduction of the MAb dose as well as of the infusion rate. Two patients achieved complete remission. One patient had a minor response, and 3 other patients were considered to have stable disease > 3 months.

Adolescent↗

Low dose cyclophosphamide, alpha-interferon and continuous infusions of interleukin-2 in advanced renal cell carcinoma.

Pretreatment with a low dose of cyclophosphamide (CY) has been claimed to inhibit suppressor functions and augment various immune functions. A combination of a low dose of CY, alpha-interferon (IFN-alpha) and continuous infusion of interleukin-2 (IL-2) was used to treat patients with advanced renal cell cancer (RCC) (stage IV). Sixteen patients received four cycles consisting of CY (500 mg m-2) three days prior to daily i.m. injections of alpha-IFN (3 x 10(6) U), and continuous infusion of 18 x 10(6) IU rIL-2 for five days. The cycle interval was three weeks. Two patients had partial response (13%) (26+ and 12+ months), two had a minor response (9+ and 4 months), and three patients achieved stable disease (19+, 14+ and 8+ months). No patients required intensive care. Side effects were mainly fever, malaise, capillary leak syndrome and diarrhoea. Non-responders showed significantly higher eosinophil and platelet counts compared to responders. Serum concentration of IL-2 was significantly higher in responders. 5/11 patients had abnormally low values of serum thyroxine after therapy. Two patients needed thyroid hormone substitution. The difference between the initial and the lowest thyroxine values correlated significantly to survival (p < 0.03). The addition of CY to rIL-2 and IFN-alpha in the present protocol did not contribute to an increased major response rate.

Adolescent↗

Mitoxantrone, etoposide, cytarabine and prednisone as salvage therapy for refractory non-Hodgkin lymphoma (NHL) and alternated with CHOP in previously untreated patients with NHL.

The treatment of relapsing or refractory high-grade malignant non-Hodgkin lymphoma (NHL) following CHOP chemotherapy remains a challenge for the clinician. In this study, 29 patients with relapsing or refractory high- or refractory low-grade malignant NHL received a combination of mitoxantrone 12 mg/m2 i.v. on days 1-2, cytarabine 100 mg/m2 i.v., b.d. d 1-2, etoposide 100 mg/m2 i.v. d 1-3 and prednisone 100 mg/m2 orally d 1-3 (ENAP). An overall response rate of 55% encouraged us to use ENAP alternated with conventional CHOP chemotherapy in 45 previously untreated NHL patients (35 with high-grade and 10 with "aggressive" low-grade malignant NHL). All patients responded with a complete remission rate (CR) of (27%) and a partial remission rate (PR) of 73% after only one course of ENAP. After a median number of 3.5 ENAP/CHOP courses, the CR and PR rate was 69 and 22%, respectively. Myelosuppression was pronounced and fever of unidentified origin and documented infections followed 59% of all cases given ENAP courses. In the last 19 previously untreated patients mitoxantrone was given at a dose of 10 mg/m2 on d 1 and cytarabine 100 mg i.v., b.d. during d 1-2. Nonhematologic toxicity was mild. We conclude that this novel chemotherapy program is effective both as first-line and salvage treatment in patients with high-grade malignant NHL. Furthermore, ENAP appears clinically to be partly non-cross resistant with CHOP chemotherapy. The dose-limiting toxicity is myelosuppression. The combination should be explored as primary therapy in combination with other chemotherapy or radiotherapy programs.

Adult↗

Therapy of colorectal carcinoma with monoclonal antibodies (MAb17-1A) alone and in combination with granulocyte monocyte-colony stimulating factor (GM-CSF).

A mouse monoclonal antibody (MAb17-1A) (IgG2A) against colorectal carcinoma cells was used to treat patients with metastatic disease. Major direct effector functions of MAb seem to be ADCC (antibody dependent cellular cytotoxicity), CDC (complement dependent cytolysis) and apoptosis ('programmed cell death'). Thus, a high tumor cell saturation of the MAb should be achieved. Increasing doses of MAb to the patients increased the total area under the concentration curve and thus the exposure of tumor cells to MAb. However, the response rate (with complete + partial + minor response + stable disease defined as response) was not augmented. In total, 10/52 (19%) patients responded and in fact lower doses (less than 2 g) might induce a higher response frequency (9/52) than higher doses (greater than 2 g) (1/52). During treatment, the numbers of cytotoxic cells (lymphocytes and monocytes) increases in the tumor lesion and complement components were deposited. As ADCC may be important, effector mechanism attempts were made to augment the cytolytic capability of the effector cells by simultaneously giving the patients GM-CSF. The combination of MAb17-1A + GM-CSF augmented the ADCC activity of blood mononuclear cells and a heavy infiltration of monocytes could be noted in the tumor. Out of 15 available patients 6 (40%) showed a response.

Antibodies, Monoclonal↗

Treatment of myelodysplastic syndromes with retinoic acid and 1 alpha-hydroxy-vitamin D3 in combination with low-dose ara-C is not superior to ara-C alone. Results from a randomized study. The Scandinavian Myelodysplasia Group (SMG).

63 evaluable patients with myelodysplastic syndromes (MDS) and 15 with acute myelogenous leukemia (AML) were randomized between low-dose ara-C (arm A) and low dose ara-C in combination with 13-cis-retinoic acid (13-CRA) and 1 alpha-hydroxy-vitamin D3 (1 alpha D3) (arm B). 69 patients were evaluable and 18 (26.1%) responded to therapy. The addition of 13-CRA and 1 alpha D3 had no positive influence on survival of the patients, remission rates or duration of remissions. 12/27 patients in arm A and 6/29 patients in arm B progressed from MDS to AML during the course of the study (p = 0.0527). Arm B gave significantly more side-effects than arm A (p = 0.005). Therapeutic effects of 13-CRA and 1 alpha D3 on MDS is not supported by this study. However, an inhibiting effect on AML development in some MDS subgroups cannot be excluded.

Aged↗

Methyl-GAG, ifosfamide, methotrexate and etoposide (MIME) as salvage therapy for Hodgkin's disease and non-Hodgkin's lymphoma. The Swedish Lymphoma Study Group.

One hundred and three patients with recurrent or refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) treated with MIME (methyl-GAG, ifosfamide, methotrexate, etoposide) were retrospectively studied. Thirty-seven of the 44 patients with HD, 34/47 with high-grade malignant and 9/12 with low-grade malignant NHL were evaluable for response. Of the 37 evaluable patients with HD, 16 (43%) achieved complete remission (CR) and 4 partial remission (PR), giving a total response rate of 54%. Of the 34 evaluable patients with high-grade NHL, 5 achieved CR and 8 PR, giving a response rate of 38%. Of 9 evaluable patients with low-grade NHL, 2 achieved CR. The main toxicity was leukopenia, thrombocytopenia and infections. Twenty-six per cent of the patients developed septicaemia, which was fatal in 6 cases (6%). We conclude that MIME as salvage regimen can induce complete remissions in lymphoma patients, particularly in HD with previous heavy treatment, and that it is relatively well tolerated.

Adult↗

Flow cytometric DNA analysis: a prognostic tool in non-Hodgkin's lymphoma.

Surgical biopsies from 234 untreated patients with non-Hodgkin's lymphoma (NHL), classified according to the Kiel nomenclature, were analysed with respect to proliferative activity (S-phase) and DNA content by flow cytofluorometric (FCF-DNA) analysis. The percentage of cells in S-phase was significantly higher in lymphomas of high compared to low grade NHL (p less than 0.001). Patients with lymphomas of high grade histology and low S-phase values (less than 5.6%) achieved complete remission (CR) more often (p less than 0.05) and survived significantly longer than those with high S-phase values (p less than 0.05). In the low grade NHL group the S-phase value did not correlate to response. S-phase correlated to survival for patients with the lymphocytic (CLL & IC) (p less than 0.05) and follicle center cell (FCC) derived (p less than 0.01) but not in blastic (LB, IB, Burkitt) NHL. DNA-aneuploidy was associated with poor response to therapy and shorter CR duration in low grade NHL (p less than 0.05 for both). However, the degree of DNA-ploidy (neardiploid or aneuploid) did not correlate to survival in any of the NHL groups analysed (high- or low grade, lymphocytic, FCC derived or blastic). The Cox regression analysis indicated that the S-phase value was a stronger predictor of survival than histopathology, stage or age, especially in low grade NHL. These results suggest that S-phase analysis should be included in the clinical evaluation of NHL patients as a prognostic indicator.

DNA↗

Clonal immunoglobulin gene rearrangements in primary mediastinal clear cell lymphomas.

Cells from two patients with primary mediastinal tumors of clear cell type were characterized by immunological and molecular biological techniques. In both cases a B cell immunophenotype was suggested by the positive staining for the B1 (CD20), B4 (CD19), Leu 14 (CD22), as well as staining with other B monoclonal antibodies by immunohistochemistry. However, no definitive evidence for the expression of Ig light or heavy chains at the protein level was found. Southern blot analysis of Ig heavy and light chain gene rearrangements revealed clonal B cell populations in both cases. There was no indication of a somatic joining of T cell receptor (TCR) genes using probes for TCR beta and or TCR gamma genes. Thus, our results suggest a clonal B cell origin of clear cell lymphomas in the mediastinum.

Antigens, Differentiation↗

Prognostic significance of immunoglobulin isotype expression in B-cell non-Hodgkin's lymphoma.

Lymph node biopsies from 170 patients with untreated non-Hodgkin's lymphomas (NHL) of B-cell type were immunophenotyped and analyzed for the Ig heavy and light chain isotypes and their relation to prognosis. IgM alone was more frequently seen in high grade (53%) compared to low grade (20%) NHL. In contrast, IgM/IgD isotypes were more frequent in low grade (47%) than in high grade NHL (20%). IgG or IgA heavy chain, alone or in combination with other heavy chain isotypes, were expressed with the same frequencies in both low (32%) and high (27%) grade NHL. Clonally restricted kappa light chain expression was noted in 64% of low grade and 66% of high grade NHL patients. Only in chronic lymphocytic leukemia (CLL) and immunocytoma (IC) was a shorter survival time noted for patients with tumors expressing IgG and/or IgA heavy chains compared to those expressing IgM or IgM/IgD (P less than 0.001). This difference was not seen as being low grade follicle center cell-derived (FCC) or high grade NHL. The expression of kappa light chains on the tumor cells was associated with a significantly longer survival in CLL and IC patients only (P less than 0.01).

Adult↗

Human herpesvirus-6 (HHV-6, HBLV) in sarcoidosis and lymphoproliferative disorders.

Serologic studies were done to estimate the antibody prevalence against human herpesvirus 6 (HHV-6) in patients with malignant lymphomas, Sjögren's syndrome and sarcoidosis. Serologic studies showed IgG antibody titers against HHV-6 in up to 41% of patients with sarcoidosis, 50-70% with malignant lymphomas and in 36% with Sjögren's syndrome. In situ hybridization on lymph node biopsies was positive for HHV-6 genome in 1 out of 5 sarcoidosis lymph nodes.

Antibodies, Viral↗

Effect of human blood mononuclear cell populations in antibody dependent cellular cytotoxicity (ADCC) using two murine (CO17-1A and Br55-2) and one chimeric (17-1A) monoclonal antibodies against a human colorectal carcinoma cell line (SW948).

Peripheral blood mononuclear cells (PBMC) from healthy individuals were studied for their lytic capability in ADCC using SW948 (a human colorectal carcinoma cell line) as target cells. Three monoclonal antibodies (MAbs) were used: two mouse MAbs (IgG2A) against the antigenic structures CO17-1A and BR55-2 respectively and one chimeric MAb 17-1A (IgG1) (mouse-human). Three kinds of effector cells were prepared. PBMC were purified on a Ficoll-Isopaque gradient (FIP cells) (a mixture of lymphocytes and monocytes). To obtain pure monocytes (greater than 90%), PBMC were centrifuged on a Nycodenz gradient (Nycodenz cells). Highly purified lymphocytes (greater than 98%) were obtained by treatment of FIP cells with iron powder and removal of phagocytic cells (PBL cells). Monocytes had the highest lytic capability. FIP cells were less effective than monocytes. PBL cells had the poorest killing activity. In reconstitution experiments addition of increasing amount of monocytes to PBL resulted in an augmented cytotoxicity. The numbers of Leu-M3+ cells, Leu-M5+ cells (monocytes) and CD16+ cells correlated positively to cytotoxicity. Higher concentration of MAb 17-1A was required to reach the same level of cytotoxicity using FIP cells as effector cells as compared to monocytes. MAb BR55-2 induced the same cytotoxic activity as MAb 17-1A. Combination of these two MAbs did not increase the lytic capability. Chimeric MAb 17-1A mediated ADCC in a dose-dependent fashion. The chimeric MAb was consistently more effective than the mouse MAb.

Animals↗

Therapeutic effects of low-dose cytosine arabinoside, alpha-interferon, 1 alpha-hydroxyvitamin D3 and retinoic acid in acute leukemia and myelodysplastic syndromes.

62 evaluable patients with myelodysplastic syndromes (MDS) or acute leukemia were treated with different combinations of low dose ara-C, alpha-interferon (IFN), 1 alpha-hydroxyvitamin D3 (vit D3) and retinoic acid. The aim was to study the efficacy and toxicity of each combination. The overall rate was 44%. Of these, 50% responded favorably to the combination of IFN, vit D3 and retinoic acid (IDR), which was comparable to the response rate of 43% for low-dose ara-C. The results of the IDR treatment may be explained by additive or synergistic effects between the separate drugs in the combination. Ara-C and IDR treatment was generally well-tolerated but interferon gave more side effects than any other drug used in the study. Evaluation of the full combination of ara-C, IFN, vit D3 and retinoic acid was not possible because of toxicity. Marrow hypoplasia was infrequent (5/27 patients) in cases responding favorably to treatment. Complete remissions were not longer than partial remissions or significant responses.

Actuarial Analysis↗

Blood clonal B cell excess (CBE) at diagnosis in patients with non-Hodgkin lymphoma (NHL). Relation to clinical stage, histopathology and response to treatment.

Untreated non-leukemic (lymphocytes less than or equal to 4.0 X 10(9)/l) patients with non-Hodgkin lymphoma (NHL) of B cell type often show an excess of B cells in peripheral blood bearing the same light chain isotype as the lymph node tumor cells which may indicate a leukemic spread of the disease. The ratio between kappa- and lambda-bearing lymphocytes (normal range 1.0-3.3) was studied to evaluate the prognostic significance of clonal B cell excess (CBE) at diagnosis in 110 NHL patients. In total 43% had a CBE in peripheral blood. Fifty-two per cent of the patients in clinically advanced stages had CBE and 30% of the patients in stages I and II. CBE was detected in 49% of all patients with low-grade malignant lymphoma and in 32% with high-grade malignancy. Patients with a normal kappa:lambda ratio at diagnosis entered complete remission more often than those with CBE (P less than 0.01). In patients with high-grade but not with low-grade malignant lymphomas remission duration was longer for those with normal kappa:lambda distribution than for the patients with an abnormal ratio (P less than 0.01). Survival was not statistically significantly influenced.

Adult↗

Blood clonal B cell excess at diagnosis in multiple myeloma: relation to prognosis.

112 patients with multiple myeloma have been studied at diagnosis for the presence of blood clonal B-cell excess (CBE), defined as a ratio between kappa+ and lambda+ lymphocytes outside the normal range (0.9-3.5). 48 patients (43%) had CBE. The increase in light chain-bearing lymphocytes was always that of the M component light chain isotype. The proportions of patients exhibiting CBE were the same in different stages. The response frequency was not influenced by the presence of CBE. However, patients with CBE had a shorter remission duration time (p less than 0.001) and total survival (p less than 0.05) than those without CBE. This was also noticed when each clinical stage was analyzed separately. Moreover, survival was shorter in patients with a large fraction of CBE than in those with a small one. Cox regression analysis revealed that CBE was a much stronger predictor of remission duration than age, clinical stage and renal dysfunction. CBE and response to initial treatment independently were the best factors to indicate survival. It is suggested that analysis of CBE should be included in the clinical characterization of untreated patients with multiple myeloma.

Adult↗