Yoshihisa Kodera

Single clonal origin of neoplastic B‐cells with different immunoglobulin light chains in a patient with Richter's syndrome

A 71‐year‐oldman was found to have chronic lymphocytic leukemia (CLL) and diffuse large cell lymphoma (DLC) simultaneously and was diagnosed as Richters syndrome. The CLL had mu lambda surface immunoglobulin (sIg) whereas the DLC had mu kappa sIg. However, the immunoglobulin (Ig) gene rearrangement and surface marker analysis demonstrated that both CLL and DLC had identical rearrangement patterns of the Ig heavy chain (IgH) and identical surface markers CD5+, CD19+, and CD20+. These facts imply that in this case the two malignancies are of single clonal origin initially, and that different sIg of CLL and DLC do not, therefore, necessarily indicate the biclonality of these malignancies. The origin of DLC in Richters syndrome remains controversial. This case suggests difficulty in concluding the biclonality of these malignancies. for a conclusion on clonality to be definitive, there is a need for cloning and nucleotide sequencing of rearranged Ig genes in more patients with Richters syndrome.

Treatment of plasma cell neoplasm with recombinant leukocyte A interferon and human lymphoblastoid interferon

SummaryThisty cases of plasma cell neoplasms (24 multiple myeloma, one plasma cell leukemia, and three primary macroglobulinemia) were treated with two kinds of highly purified α-interferons, recombinant human leukocyte interferon (rIFN-αA) (16 cases) and human lymphoblastoid interferon (HLBI) (14 cases). Partial remission (PR) was obtained in two of 16 evaluable cases treated with rIFN-αA and in two of 12 evaluable cases treated with HLBI. If minor response (MR) was included, responses were observed in seven (31.3%) and six (50%), respectively. Response (PR+MR) was noted in 38% of 21 previously treated patients and 71% of seven previously untreated patients. Side-effects were noted in more than two-thirds of the patients. They included fever, malaise, nausea/anorexia and myelosuppression. Thus, these two kinds of highly purified α-interferon were effective in plama cell neoplasm, producing unequivocal response in 14.3% of the cases without unacceptable side-effects.

Randomized controlled study of chemoimmunotherapy of acute myelogenous leukemia (AML) in adults with Nocardia Rubra cell‐wall skeleton and irradiated allogeneic AML cells

The effect of immunotherapy with Nocardia rubra cell‐wall skeleton (N‐CWS) on remission duration and survival of adults with acute myelogenous leukemia (AML) was studied in a prospective randomized controlled study. After having been induced into complete remission and having been consolidated, 73 patients were randomized either to maintenance chemotherapy or maintenance chemotherapy plus immunotherapy with N‐CWS and irradiated allogeneic AML cells. Thirty‐four patients in the chemotherapy group and 32 in the chemoimmunotherapy group were evaluable. Six months after the closure of the study, the immunotherapy showed a borderline beneficial effect on remission duration (P = 0.080) and on survival length (P = 0.098). When the data were analyzed at 30 months after the entry, there was a borderline significant difference in remission duration (P = 0.080) between the two groups, prolonging the 50% remission period by 110 days; but no significant difference in survival length (P = 0.314), although the 50% survival was 168 days longer in the chemoimmunotherapy group. However, there were 4 (18.2%) 5‐year relapse‐free survivors among 22 patients (11 in each group) who had been diagnosed more than 5 years before the time of the present analysis, and all of them belonged to the chemoimmunotherapy group (P = 0.090). Thus, immunotherapy with N‐CWS and irradiated allogeneic AML cells seems to be active in the treatment of adult AML when used for maintenance therapy in combination with chemotherapy. Cancer 57:1483–1488, 1986.

Inactivation of the mitogenic property of pokeweed mitogen by erythrocytes

In whole blood culture, pokeweed mitogen (PWM) is unable to stimulate human lymphocytes. This is because the mitogenic property of PWM is inactivated by erythrocytes, presumably due to absorption. The inactivation was observed with as few as 5 x 10(6)/ml of human erythrocytes. Therefore, when PWM is used to study the functions of human lymphocytes, especially of suppressor T lymphocytes, erythrocytes should be removed from lymphocyte preparations for accurate analysis.

EXPERIMENTAL MODELS AND THE ROLE OF RNA IN IMMUNOTHERAPY OF LEUKEMIA

Ribonucleic acid (RNA) fraction extracted from lymphoid tissues of immunized animals has been shown to transform normal, nonimmune lymphoid cells to immunocompetent Alexander and coworkers reported that primary rat sarcoma regressed after the injection of nucleic acid extracted from the lymphocytes of sheep and allogeneic rats which had been immunized with the tumor to be treated.6 Rigby observed the prolonged survival of mice bearing Ehrlich ascites tumor by administering syngeneic spleen cells incubated with RNA extracted from spleens of syngeneic mice which had been immunized with this tumor.; Ramming and Pilch showed that the growth of isografts of a chemically induced murine sarcoma was inhibited by the injection of syngeneic spleen cells incubated with RNA extracted from guinea pigs immunized with the same mouse tumor. The inhibitory effect was, at least partially, tumor-specific and did not cross-react with the other chemically induced

Intensive Induction Therapy with Behenoyl, Cytosine Arabinoside, Daunorubicin, and 6-Mercaptopurine Followed by Intensive Consolidation with Mitoxantrone, Etoposide, Vincristine, and Intermediate-Dose Continuous Cytarabine (M-85 Protocol) for Adult Acute Myelogenous Leukemia

Over 70% of adults with acute myelogenous leukemia (AML) are induced into complete remission (CR) [1-4]. Our current target is not only to increase the remission rate, but to increase the cure rate of this disease, hopefully to over 50%. Two previous protocols for adult AML in our hospitals, BHACDMP [2] and BHAC-DMP (II) [4], from 1979 to 1985 showed that the percentage of blasts in the bone marrow at 2 weeks after the start of therapy is the most significant prognostic factor for predicting longer continuing CR by a multivariate analysis. However, in BHAC-DMP (II), where we gave very intensive induction therapy to reduce blasts in the marrows as quickly as possible, we were forced to stop this protocol because of a high incidence of severe infections, especially aspergillosis and other fungal infections, owing to prolonged myelosuppression during the induction period.

Augmentation of generation of human allospecific cytotoxic T lymphocyte by PPD in in vitro sensitization culture.

SummaryPPD augmented human lymphocyte blastogeneic response to allogeneic lymphocytes in the mixed lymphocyte reaction (MLR) and generation of human cytotoxic lymphocytes against allogeneic human lymphocytes in in vitro sensitization (IVS) culture. The augmenting effect of PPD in the MLR was unequivocally synergistic at its lower concentrations (0.05 and 0.01 μg/ml). The augmentation of MLR was observed following addition of a supernatant of culture medium of lymphocytes which had been precultured with PPD for 24 h then washed free of PPD and recultured without PPD for another 24 h. PHA and Con A, in contrast, suppressed both MLR and the generation of alloreative cytotoxic cells. The alloreactive cytotoxic lymphocytes whose generation was augmented by PPD belonged to the SRBC-rosette forming fraction and passed through a nylon-wool column. The NK cell-like activities of the alloreactive cytotoxic lymphocytes were not augmented by PPD. Analysis of the alloreactive cytotoxic lymphocytes whose generation was augmented by PPD by competitive inhibition assay with unlabeled cells indicated that the same allogeneic lymphocytes used as sensitizing cells in IVS culture inhibited the cytotoxicity, while MOLT-4 cells, which are frequently used as target cells for the human NK-cell assay, did not. When lymphocytes with known HLA-A and HLA-B were used in the IVS culture and the cytotoxicity assay, PPD was found to augment the cytotoxicity only against the target lymphocytes that possessed the same HLA as the sensitizing lymphocytes in IVS.