okamoto masataka

Purpose: Rituximab is an anti-CD20 monoclonal antibody, and it is used to treat B-cell lymphomas. Antibody-dependent cellular cytotoxicity (ADCC) is considered one of the mechanisms through which rituximab exerts its effects. Granulocyte colony-stimulating factor (G-CSF) enhances the cytotoxicity of neutrophils through ADCC, and it can be speculated that a combination of rituximab and G-CSF may augment the treatment efficacy of rituximab. Experimental Design: We administered rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) treatment with G-CSF to 15 patients with follicular lymphoma, and we investigated the safety and efficacy of this regimen. We investigated ADCC activity in neutrophils and the expression of cell surface antigens including Fcγ receptor type I [FcγRI (CD64)] on neutrophils to determine the optimal dose of G-CSF. Results: Adverse reactions occurred in 14 of 15 patients and consisted mainly of grade 3/4 hematological toxicity. The response rate was 100%, with complete remission in 12 patients (80%) and partial remission in 3 patients (20%). At 14 months, the median length of the observation period, 2 of 12 patients had relapsed. G-CSF administration increased both FcγRI expression and ADCC activity. There were no significant differences in the levels of FcγRI expression or ADCC activity between the 2 μg/kg G-CSF and 5 μg/kg G-CSF groups, indicating that the optimal dose of G-CSF was 2 μg/kg. Conclusions: We conclude that the combination of rituximab-CHOP and G-CSF is well tolerated. We plan to carry out a randomized trial to compare efficacy between rituximab-CHOP treatment and treatment with a combination of rituximab-CHOP and G-CSF.

Purpose: Recently, we established an ELISA technique for measuring nm23-H1 protein in serum and found that the serum nm23-H1 level is a potential prognostic factor for patients with non-Hodgkin's lymphoma. Experimental Design: We used immunohistochemistry to examine the expression of nm23-H1 by the lymphoma cells in patients with diffuse large B-cell lymphoma (DL-BCL). Results: By analyzing a consecutive series of 172 untreated DLBCL patients, we found that 100 (58.1%) were strongly positive. The cytoplasmic nm23 expression in lymphoma cells correlated significantly with the serum nm23-H1 level. There was a significant correlation between patients with cytoplasmic nm23-positive lymphoma and those with performance status 2-4, stage III/IV, bulky mass, B symptoms, elevated serum level of soluble interleukin 2 receptor, and elevated serum level of C-reactive protein. Overall and progression-free survival rates were significantly lower in patients with nm23-H1-positive lymphomas than in those with nm23-H1-negative lymphomas. Similar difference was seen between patients with high and low serum levels of nm23-H1. Thus, the correlation between presence or absence of cytoplasmic nm23-H1 expression and serum nm23-H1 levels suggests that serum nm23-H1 is produced directly by lymphoma cells. Conclusion: We suggest that nm23-H1 expression is a prognostic factor for DLBCL, and that it is as important as serum nm23-H1, both of which are useful for planning a treatment strategy.

We recently demonstrated that the prognosis for de novo CD5-positive (CD5(+)) diffuse large-B-cell lymphoma (DLBCL) is markedly worse than that for CD5-negative (CD5(-)) DLBCL. Our findings also suggested that on the basis of its clinical features CD5(+) DLBCL may constitute a unique disease category. However, the genetic basis for these two categories has not been established. Therefore, we performed comparative genomic hybridization analysis (CGH) of 26 cases of CD5(+) DLBCL and 44 cases of CD5(-) DLBCL. Several identical changes in CD5(+) and CD5(-) DLBCLs were found, such as gains of 3q, 9p, 12q, 13q, and 18q and losses of 1p ,6q, 17p, and 19p. However, distinct differences between the two categories were also detected. These included gains of 11q21-q24 (P = 0.032) and 16p (P = 0.005) in CD5(+) DLBCL, and loss of 16p (P = 0.028) in CD5(-) DLBCL. A comparison with results reported for mantle cell lymphoma, chronic lymphocytic leukemia, and Richter's syndrome demonstrated that the CGH pattern of CD5(+) DLBCL was markedly different. This indicates that CD5(+) DLBCL constitutes a disease category distinct from that of CD5(-) DLBCL and other CD5(+) malignancies. (C) 2003 Wiley-Liss, Inc.

We have reported previously that the serum nm23-H1 level is a prognostic factor for non-Hodgkin's lymphoma. In this study, we examined nm23-H1 expression in T- and natural killer (NK)-cell lymphoma in order to evaluate whether lymphoma cells produce the protein. The clinical significance of the cytotoxic molecules, T-cell intracellular antigen-1 (TIA-1) and granzyme B and nm23-H1 expression were also examined. Expression of nm23-H1, TIA-1, or granzyme B was examined by immunohistochemistry in 137 previously untreated lymphoma patients. The relationship between the results and clinical outcome was examined in 81 patients with angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, or peripheral T-cell lymphoma, unspecified. The neoplastic cells of some lymphomas produced nm23-H1 and the expression rates of nm-23-H1, TIA-1 and granzyme B were 36.5%, 78.8% and 32.8% respectively. The nm23-H1-positive or TIA-1-positive groups had significantly shorter overall and disease-free survivals. Multivariate analysis confirmed nm23-H1 expression to be an independent prognostic factor. The nm23-H1 protein can be an important prognostic factor in the lymphomas studied here. New treatments that target nm23 overexpression could be developed as a result of nm23-HI production by lymphoma cells.

Therapeutic approaches for non-Hodgkin's lymphoma (NHL) are currently based on the International Prognostic Index (IPI). Research on biological prognostic factors has been actively pursued in recent years, with serum vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) being identified as prognostic factors for NHL. Here, we determined that serum VEGF and IL-6 levels are independent prognostic factors for aggressive lymphoma. Compared with normal controls, serum VEGF and IL-6 levels were significantly higher in patients with aggressive lymphoma or adult T-cell leukemia/lymphoma. Furthermore, overall and disease-free survival rates for patients with high levels of VEGF or IL-6 were significantly poorer than for patients with low levels. In addition, the prognosis for patients with high levels of both serum VEGF and IL-6 was significantly poorer than that for patients with high levels of either VEGF or IL-6 or with low levels of both VEGF and IL-6. Multivariate analyses of a variety of prognostic factors, including the five IPI factors, revealed that serum VEGF and IL-6 were both independent prognostic factors for overall survival of aggressive lymphoma. Therefore, a combination of VEGF and IL-6 represents a useful prognostic factor for aggressive lymphoma.

Extranodal marginal-zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT) arising in the thymus is rare, with the largest series in the literature including only three cases. In the present study, we investigated 15 cases of thymic MALT lymphoma to systematically characterize its clinical, histopathological, and molecular features. There was a marked female predilection (male:female = 1:4), with a mean age of 55 years at diagnosis. There was a strong association with autoimmune disease, especially Sjögren's syndrome. Histologically, the thymic lymphoma showed the characteristic morphological features of extranodal MZBL of MALT type. Cysts were common. Prominent lymphoepithelial lesions were formed by centrocyte-like cells infiltrating and expanding the Hassall's corpuscles and epithelium lining the cysts. Plasmacytic differentiation was apparent in all cases. Notably, 13 of 15 cases expressed immunoglobulin (Ig) A phenotype IgA expression in thymic MALT lymphoma was in striking contrast with the IgM phenotype observed in most of the Sögren's syndrome-associated MZBLs and MALT lymphomas at other sites. Epstein-Barr virus was absent, and API2-MALT1 gene fusion, a recently reported MALT lymphoma-specific gene abnormality, was not detected in any case. Although one patient died of disease 85 months after the diagnosis, other patients were alive with overall 3-year and 5-year survival rates being 89% and 83%, respectively. Among the 22 patients reported previously and in the present series, at least 17 patients (77%) were Asians. These data indicate that thymic MALT lymphoma may represent a distinct subgroup of MALT lymphoma characterized by apparent predilection for Asians, a strong association with autoimmune disease, frequent presence of cysts, consistent plasma cell differentiation, tumor cells expressing IgA phenotype, and consistent lack of API2-MALT1 gene fusion.

Advances in chemotherapy have led to a favorable long-term prognosis in approximately 50% of patients with aggressive non-Hodgkin lymphoma (NHL). However, the remaining patients do not enjoy such prolonged survival after standard treatment. New prognostic factors are needed to define this poor-prognosis group and to plan an appropriate treatment strategy. It has been reported that serum nm23-H1 protein may be a new prognostic factor for aggressive NHL. In the present study involving multiple institutions and a large number of patients, the level of nm23-H1 protein was compared among different types of lymphoma It was lowest for indolent lymphoma, followed by aggressive lymphoma and then highly aggressive lymphoma. In addition, patients with aggressive NHL and higher nm23-H1 levels had worse overall and progression-free survival rates than those with lower nm23-H1 levels. The nm23-H1 level was also compared between patients with diffuse large B-cell lymphoma and patients with peripheral T-cell lymphoma. The results suggest that the level of nm23-H1 could serve as a prognostic factor in both groups. Moreover, the prognosis of lymphoma patients could be ascertained even more precisely by combining soluble interleukin-2 receptor or soluble CD44 and nm23-H1 levels. A multivariate analysis confirmed that the nm23-H1 level is an independent and important prognostic factor in aggressive NHL. Therefore, it may provide useful information for clinicians to determine the appropriate therapy for each type of lymphoma. © 2001 by The American Society of Hematology.

Standard chemotherapy has been ineffective for improving the poor 10-year survival rate of patients with indolent lymphoma. However, a wider choice of therapeutic modalities has become recently available, including immunotherapy with monoclonal antibodies and allogeneic peripheral blood stem cell transplantation. Accordingly, a sensitive prognostic indicator is required to identify high-risk patients and to help design new therapeutic approaches for them. We previously reported that the serum nm23-H1 protein level was an independent prognostic factor for aggressive lymphoma. The present study was performed to assess the clinical implications of this protein on indolent lymphoma and whether it can be used to classify the aggressiveness of the disease in order to assist in the individualization of therapy. A total of 130 patients with indolent lymphoma were enrolled in this multicenter study. The serum nm23-H1 protein level was significantly higher in patients with indolent lymphoma than in a normal control group. In addition, indolent lymphoma patients with higher nm23-H1 levels had worse overall and progression-free survival rate than those with lower nm23-H1 levels. Therefore, nm23-H1 in serum may be useful for identifying a distinct group of patients at high risk.

We conducted a multi-institutional collaborative study to examine the usefulness and safety of third-generation chemotherapy CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) combined with granulocyte colony-stimulating factor (G-CSF) in the treatment of aggressive non-Hodgkin's lymphoma (NHL). Subjects included patients with aggressive NHL who were 60 yr of age or younger and had been diagnosed as having a low-intermediate, high-intermediate, or high risk using the International Prognostic Index (IPI). A total of 24 patients were enrolled in the study between May 1997 and March 1998, including 9 low-intermediate-risk cases, 13 high-intermediate-risk cases and 2 high-risk cases. Although all 24 patients were originally enrolled in the study, one adult T-cell leukemia/lymphoma case was subsequently excluded. Thus, in the end, 23 cases were evaluated. Evaluation of the efficacy of therapy revealed complete remission in 20 patients (87%). Of these 20 patients, 8 were low-intermediate-risk cases (89%) and 12 were either high-intermediate or high-risk cases (86%). Partial remission was achieved in 2 patients (8.7%). The 2-yr survival rate was 91.3%, and the 2-yr disease-free survival rate was 81.8%. Grade 3 or higher adverse reactions were granulocytopenia (87%), thrombocytopenia (17.4%) and liver dysfunction (4.3%). CyclOBEAP therapy has been associated with a high remission rate for aggressive NHL. When combined with G-CSF, a high relative dose intensity was maintained for each drug administered (0.94-0.97). Furthermore, although the observation period was short, both the survival rate and disease-free survival rate were good. Hence, we concluded that there were no problems associated with the procedure in terms of safety.

A 50-year-old man noticed a mass in the right cervical region and presented to our hospital. He underwent biopsy of a cervical lymph node, which revealed non-Hodgkin's lymphoma (diffuse large B cell, lymphoblastic type) histologically. He was treated with chemotherapy (CHOP) and radiation, and achieved complete remission. Two months later, he was admitted because of distal pain and extensive numbness of the lower limb as well as weakness of the left leg. Lumbar MRI showed an area of abnormal intensity in the cauda equina. Cytological examination of cerebrospinal fluid showed class V (lymphoma cells), so he was diagnosed as having recurrent malignant lymphoma of the spinal cord. He was treated with intrathecal chemotherapy and irradiation. After the treatment the mass in the cauda equina disappeared and the neurological symptoms in his legs resolved. It is rare for malignant lymphoma to reccurr in the spinal cord, particularly the cauda equina. It is well known that cauda equina syndrome can be caused by vertebral lesions and primary spinal cord tumors, but it is also necessary to keep malignant lymphoma of the cauda equina in mind.

An acute leukemia with an unusual immunophenotype developed in a 17-year-old girl. At the initial presentation, extramedullary involvement was not evident, but with advancing disease, massive splenomegaly and an osteolytic rib tumor developed. The disease was aggressive and refractory to intensive chemotherapeutic regimens for myeloid and lymphoid malignancies, and the patient died 3 months after the initial presentation. The leukemic cells were of irregular shape and variable size they had deeply indented or bi-lobed nuclei and relatively fine, azurophilic granules in their cytoplasm. They were positive for acid phosphatase and β-glucuronidase in granular staining, but they were negative for myeloperoxidase. The leukemic cells had a unique immunophenotype: it was positive for T-cell antigens (CD1a, CD2, cytoplasmic CD3, CD4), myeloid antigens (CD13 and CD33), NK-cell antigen (CD56), CD19 and CD30. DNA analysis revealed no gene rearrangement in the T-cell receptor β, γ and δ, or immunoglobulin heavy chain genes. The leukemic cells of our patient are thought to have arisen from the transformation of a putative precursor cell common to both the T- and NK-cell lineage in the bone marrow. The current literature on precursor NK-cell malignancy is reviewed, and its clinicopathological feature is discussed.

We report a case of severe aplastic anemia (SAA) treated with granulocyte colony-stimulating factor (G-CSF), cyclosporin A and danazole, in which myelodysplastic syndrome (MDS) with monosomy 7 developed eight months later. A 24-year-old woman was diagnosed as having SAA and was initially treated with G-CSF, cyclosporin A and danazole. At initial presentation, bone marrow aspirate revealed marked hypocellularity with a normal karyotype (46, XX [20]) and no MDS features. Eight months after initial treatment, leukocytosis and reticulocytosis were observed and bone marrow aspirate showed hypercellular marrow with morphological and cytogenetic features (45, XX, -7 [16]/46, XX [4]) characteristic of MDS (refractory anemia). A total of 75mg (1.25mg/kg) of G-CSF had been administered during the preceding eight months. Among seven previous reports published in Japan since 1992, in which MDS/acute myelogenous leukemia (AML) developed from SAA treated with G-CSF, six showed monosomy 7. Careful observation for leukemic transformation is therefore indicated in patients with SAA who are treated with G-CSF.

A 53-year-old man with severe aplastic anemia developed sporadic Vibrio vulnificus septicemia 1 day after eating raw fish and shellfish. Although V. vulnificus infection is potentially fatal, he was saved by immediate and sensitive antibiotic administration. Patients with chronic hematologic disease are susceptible to infection by this organism and are prone to developing septicemia when they eat raw seafood. It is necessary for a patient with this infection to be given effective antibiotics as quickly as possible.

Thirty-two adults (median age 48 years) with acute myelogenous leukemia (excluding M3) have been treated with short-term intensive therapy (M90 therapy). After induction therapy with daunorubicin, cytosine arabinoside (araC), 6-mercaptopurine, prednisolone, mitoxantrone (MIT) and etoposide (VP16), three regimens of post-induction chemotherapy were conducted as short an intercycle time as possible. The first regimen was with MIT and VP16, the second with behenoyl-araC and aclarubicin and the third with VP16, araC, vincristine and vinblastine. No further therapy was given. Complete remission was achieved in 24 (75%) of 32 patients and 24% of all patients were projected to remain free of disease at 5 years. The median duration of the entire therapy was 120 days with a range of 95 to 157 days. Post-induction regimens resulted in severe myelosuppression and their toxicity included treatment-related death in one patient. The treatment results of this short-term therapy were comparable to a former treatment protocol, M84 therapy with a median duration of the entire treatment therapy of 515 days. To confirm the advantages of such short-term therapy, prospective randomized comparisons with conventional post-induction therapy may be required.

A 44 year-old woman with acute myeloid leukemia (AML, FAB, M4E) developed heart failure during treatment with anthracyclines for AML. She had not experienced heart disease and her left ventricular ejection fraction (LVEF) was 59% at the end of a successful remission induction therapy. Because her LVEF decreased to 33% after early consolidation therapy, the chemotherapy for AML was discontinued. The cumulative dose of daunorubicin, aclarubicin and mitoxantrone was 486 mg/m², 135 mg/m² and 55 mg/m², respectively. In October 1990, four months after the end of the chemotherapy, heart failure (class III, NYHA) developed and did not improve by treatment consisting of dobutamin, digoxin and diuretics. Anthracycline cardiomyopathy was histologically confirmed by endomyocardial biopsy. Then we administered selective β1-antagonist, metoprolol (Seloken^®), with an initial dose of 5 mg/day which was doubled 3 times every 4 or 8 weeks to 40 mg/day, according to the treatment schedule of dilated cardiomyopathy. She recuperated satisfactorily (Class I, NYHA), and was discharged on February '91. Her LVEF gradually improved and it has been maintained at above 50% on an outpatient basis. The patient has been in complete hematological remission during this period. It seems that low dose selective β1-antagonist therapy has a potential to improve myocardial function in some patients with anthracycline cardiomyopathy.

We evaluated the in vitro proliferative response to exogenous IL-1β in terms of tritiated thymidine (3H-TdR) incorporation in leukemic cells obtained from 119 patients with various types of acute leukemia. The content of IL-1β in leukemic cells was measured by enzyme-amplified sensitivity immunoassay. We observed a significant proliferative response to exogenous IL-1β in leukemic cells from 27 66 patients with de novo AML, 1 29 patients with ALL, 2 3 patients with AUL, 8 12 patients with AML arising from MDS, 4 7 patients with myeloid crisis of CML, and 0 4 patients with lymphoid crisis of CML. Proliferation was marked in myeloid leukemic cells of a more premature stem cell origin. There were no significant differences in proliferative responses among the different FAB classes of de novo AML. The IL-1β content of leukemic cells was low in patients with lymphoid leukemia, but there was no significant difference among the various types of myeloid leukemia. There was no correlation between the proliferative response to exogenous IL-1β and the IL-1β content of leukemic cells. When we correlated the proliferative response to exogenous IL-1β with treatment outcome in patients with de novo AML, we found the rate of complete remission (CR) to be lower in those with a high proliferative response. We noted a longer duration of CR (p = 0.07) and of survival (p &lt 0.05) in patients with a low proliferative response. Thus, a high proliferative response to IL-1β in the cells of AML patients may indicate a poor prognosis. © 1995.

A 41-year-old woman with follicular lymphoma developed sporadic respiratory syncytial virus (RSV) pneumonia shortly after allogeneic bone marrow transplantation from an HLA-matched sibling. RSV pneumonia is potentially fatal in immunosuppressed patients, but she improved along with the recovery of bone marrow function without specific treatment. Early recovery of myelosuppression supported by granulocyte colony-stimulating factor may have helped to control RSV pneumonia.

A 43-year-old male developed acute myelogenous leukemia (AML, M5b) with an acquired Robertsonian 13 15 translocation. He did not achieve complete remission after sequential intensive induction chemotherapy and he died 13 months later. We reviewed 7 patients with this translocation reported in the literature. Acquired Robertsonian translocations are rare, but could represent an important event in the tumorigenesis of hematologic malignancies.

In order to evaluate the effect of specific immune response on prognosis in acute leukemia, we investigated the correlation between the lysis of autologous tumor cells (ATC) by lymphocytes and prognosis. Peripheral mononuclear cells (PMC) from most patients with acute leukemia in complete remission (CR) do not exhibit cytotoxic activity against fresh-frozen ATC, although they have adequate cytotoxic activity against K562 cells. When the large granular lymphocyte (LGL) fraction was used in this study, we observed lysis of ATC in 17 (43.6%) of 39 patients with acute leukemia (12 (42.9%) of the 28 patients with acute myelogenous leukemia (AML) and 5 (45.5%) of the 11 patients with acute lymphocytic leukemia (ALL)). With regard to prognosis, the lytic activity of the LGL fraction did not reflect the duration of CR. The median CR duration in AML patients was 13 months for the lysis-positive group and 11 months for the lysis-negative group. No significant correlation was also found between lytic activity of the LGL fraction and overall survival in each patient. However, the lysis-positive group tended to have a longer survival, the median overall survival being 48 months for the lysis-positive group vs 12 months for the lysis-negative group. The prolonging of overall survival in the lysis-positive group was attributed to a high rate of induction of second remissions in this group. Long-term patient survival in the two groups did not differ. © 1994.

Twenty-two patients with advanced diffuse large cell lymphoma (LSG classification) were treated with the combination chemotherapy of cyclophosphamide, doxorubicin, methotrexate with leucovorin rescue, bleomycin, vincristine, etoposide, ifosfamide and prednisolone (CAMBO-VIP) from Oct. 1987 to Sept. 1989. Eighteen (90%) of 20 evaluable patients achieved complete remission and 2 patients had partial remission. With a median follow-up of 52 mos, 3 patients relapsed (17%), and 2 patients died. The actuarial overall survival and relapse-free survival at 4 years were estimated to be 90% and 83%, respectively. Myelosuppression was severe, but transient. No serious infection was seen, and no platelet transfusion was required. Oral mucositis and liver damage (Grade 3 in WHO grading) was seen in one patient each, but no treatment-related fatalities were observed. CAMBO-VIP is a well tolerated, effective treatment regimen for advanced diffuse large cell lymphoma.

Twenty-four patients with advanced or relapsed gastric or colorectal cancer were treated with a combination of 5-fluorouracil (5-FU), leucovorin (LV) and interferon-α (IFN-α). 5-FU was administered by rapid intravenous infusion at 350 mg/m2 for 5 consecutive days. Intravenous bolus administration of LV 20 mg/m2 was given before each 5-FU administration. This combination was repeated every 3 to 4 weeks. IFN-α (HLBI), 6MU, was administered subcutaneously daily. Of 13 patients with gastric cancer, there were 2 PR, 4 NC and 7 PD, and among 11 patients with colorectal cancer, there were 1 CR, 8 NC and 2 PD. All 16 previously treated patients had no clinical response. Responses were seen in patients with no prior chemotherapy and with good performance status. Most common toxicities observed were leucopenia, fever, stomatitis and diarrhea, which were all tolerable and reversible.

We designed a post-induction therapy including intensive sequential therapy with non-cross-resistant drugs in an effort to prolong disease-free survival (DFS) for adults with acute myelogenous leukemia. Forty-five patients entered this study and 33 of 35 patients entering complete remission received the post-induction therapy. With a median follow-up for survivors of 3.5 years from complete remission, the actuarial 5-year DFS was 46% ± 19% (95% confidence interval). The five-year DFS for patients over 45 years of age was comparable to that for patients under 45 years of age (50% ± 26% vs 47% ± 28%). Furthermore, the actuarial 5-year DFS for patients who required two courses of induction therapy was comparable to that for patients who required only one course of induction therapy (45% ± 29% vs 50% ± 25%). The toxicity of post-induction therapy was tolerable and no patients died during complete remission. © 1992.

Thirty‐two patients with advanced non‐Hodgkin's lymphoma (NHL) with aggressive histologic findings were treated with cyclophosphamide, doxorubicin, methotrexate with leucovorin rescue, bleomycin, vincristine, etoposide, ifosfamide, and prednisolone (CAMBO‐VIP), in which presumably non‐cross‐resistant myelosuppressive and nonmyelosuppressive agents were administered during alternate weeks for 12 weeks. To ensure the high‐dose intensity of the protocol, dose reduction and delay in treatment were minimized. Three patients were treated inadequately. Twenty‐six (89.7%) of 29 evaluable patients had a complete response, and three had a good partial response. Relapse occurred in four patients, with a median follow‐up of 29 months. The actuarial overall survival and disease‐free survival were estimated to be 87.6% and 75.9%, respectively. The CAMBO‐VIP treatment was well tolerated myelosuppression was severe but transient and caused no serious infections. Side effects that affected dose intensity were oral ulceration, occurring in 28 patients, and blister formation under the thickened skin of palms and/or soles, followed by desquamation (5 patients). Hepatic toxicity was generally mild to moderate it was severe in one patient. A 12‐week regimen of CAMBO‐VIP was effective for advanced NHL with aggressive histologic findings. Copyright © 1992 American Cancer Society

The mixed lymphocyte-autologous tumor cell reaction (MLTR) was performed in 15 patients with hematological malignancies. Lymphocyte proliferative response and generation of cytotoxic cells against autologous tumor cells were evaluated and as was the effect of interferon-β (IFN-β) (750 IU/ml). Lymphocytes from patients during complete remission had sufficient functions in mixed lymphocyte culture with normal lymphocytes. Tumor cells stimulated allogeneic lymphocytes, although to a generally lesser extent as compared with remission lymphocytes from the same patients. Increased [3H]TdR uptake was observed in 5 patients and was suppressed by the addition of IFN-β. Autologous tumor cell kill activity was induced by MLTR in 3 patients IFN-βenhanced killing activity was present in these patients as well as in 3 other patients. Tumor cells from the 3 patients with positive autologous tumor cell kill activity had almost the same stimulating capacity as lymphocytes. The expression of MHC class I antigen and IFN-β-enhanced expression was observed in all tumor cells studied by indirect immunofluorescence. These data suggest that some factors on tumor cells, in addition to MHC class I antigen, participate in the generation of cytotoxic cells against autologous tumor cells and its enhancement by IFN-β. © 1991, Mary Ann Liebert, Inc. All rights reserved.