ALBERT

Description: Determination of the percentage of cells in clumps on a stained smear of human peripheral blood porvided a useful, accurate technique for measuring cell adhesiveness. Smears of human peripheral blood drawn with EDTA were prepared on a blood slide centrifuge, stained, and examined under a light microscope. Statistical analysis showed that the method resulted in a Poisson distribution of particles on the slide, where a particle was considered to be a simple cell, or two or more cells which appeared to be touching, Analysis of the distributions of erythrocytes and leukocytes showed that clumps were formed before the cells were deposited on the slide. When adhesiveness of erythrocytes or leukocytes was increased by incubation with antiserum to the corresponding cell type, the percentage of that cell type in clumps increased proportionately, Preliminary results using the method showed that normal human donors had similar to 1% of their erythrocytes and 1- 5% of their leukocytes in clumps. In chronic myelocytic leukemia, as many as 60% of the leukocytes were in clumps.

Description: Of 95 young non-Hodgkin's lymphoma patients entered consecutively on the National Cancer Institute (NCI) Protocol 7704, 26 (27.4%) had involvement of one or more bones. The mean age of these 26 patients was 16.6 years, and the male to female ratio was 3.3:1. Tumor histology included undifferentiated Burkitt's lymphoma in 12, undifferentiated non-Burkitt's lymphoma in two, undifferentiated, unspecified lymphoma in one, diffuse large cell lymphoma in three, and lymphoblastic lymphoma in eight patients. Most had extensive disease; two patients had isolated bone lesions, one had lesions of two bones without involvement of other tissues, and 23 had either multiple bone lesions or single bone lesions with involvement of other tissues. Eight of the 26 patients had bone marrow involvement. Of a subgroup of 12 patients with jaw disease, 11 had undifferentiated lymphoma and one had diffuse large cell lymphoma. Only one had primary a jaw tumor, with two quadrants of the jaw involved. All 26 patients were treated with chemotherapy; only two received radiotherapy initially for bone lesions. Predicted survival of the 26 patients at 5 years is 53.2%. The 12 patients who remain disease free have a mean survival of 62.1 months (range, 22 to 100 months). Our results call into question the role of radiotherapy in the treatment of bone lesions in non-Hodgkin's lymphoma.

Description: Intracellular lactate dehydrogenase (LD) isoenzyme patterns were studied in the malignant cells of patients with a variety of lymphoid malignancies. These were compared with intracellular LD isoenzyme patterns of normal lymphoid cells and were also correlated with immunologic cell surface marker characteristics. Results showed that, in general, the malignant B cells of Burkitt's lymphoma and the lymphoblasts of T-cell acute lymphoblastic leukemia had isoenzyme patterns similar to those of normal B and T cells, respectively. The isoenzyme patterns of malignant lymphoid cells from patients with non- T, and non-B acute lymphoblastic leukemia, cutaneous T-cell lymphoma, and chronic lymphocytic leukemia were more heterogeneous. These data, although based on small numbers of patients, are consistent with the hypothesis that LD isoenzymes may reflect differences in the maturational status of cells within a single diagnostic category.

Description: Cytogenetic studies were done in two cases of Burkitt's lymphoma in homosexual individuals with possible acquired immune deficiency syndrome (AIDS). The chromosomal abnormalities found are consistent with those previously described in the nonendemic form of Burkitt's lymphoma, with one of the two patients having the variant translocation, t(8;22). The production of the kappa light chain immunoglobulin by the tumor cells from the patient having t(8;22) and the occurrence of the different sites of translocation of the duplication of 1 q in the second patient are unusual findings. Whether there is an increase in the incidence of the variant translocation t(8;22) is yet to be determined.

Description: We have used a single intensive chemotherapy regimen in the treatment of young patients with diffuse, aggressive, malignant lymphomas. There were two major histologic types of lymphoma in our series: lymphoblastic lymphomas, which presented most often with mediastinal tumor (64%), and undifferentiated lymphomas (mostly Burkitt’s lymphomas), which occurred predominantly in the abdomen (86%). Our objective was to examine the determinants of prognosis in a uniformly treated patient group that included 31 children (2–16 yr) and 34 young adults 17–35 yr). Patients with extensive bone marrow involvement (greater than 50% replacement by tumor cells) were included in the study. Treatment consisted essentially of a 4-drug combination (cytoxan, adriamycin, vincristine, and prednisone) alternating with a 42-hr methotrexate infusion, followed by leukovorin rescue, and included intrathecal prophylactic therapy against central nervous system (CNS) disease. Patients with localized or resected undifferentiated lymphoma received 6 therapy cycles; all other patients received 15 cycles. Radiation therapy was used only in exceptional circumstances. Fifty-eight of 65 patients (89%) achieved complete remission: 97% of children and 82% of adults. The estimated 3-yr survival was 60% (SE 6.4%) with a median follow-up of 3 yr. Analysis of factors associated with remission duration and survival indicated that bone marrow involvement at referral and extensive disease were poor prognostic variables. Patients with lymphoblastic lymphomas and patients with completely resected undifferentiated lymphomas had the best prognosis (81% +/- 12% and 94% +/- 6% estimated 3-yr survival, respectively). Patients with extensive intraabdominal undifferentiated lymphoma (stage D) had the worst prognosis (33% +/- 11% estimated 3 yr survival), but even in this subgroup, bone marrow involvement was an adverse factor (estimated survival in stage D patients with and without bone marrow involvement was 14% +/- 13% and 43% +/- 15%, respectively). Elevated uric acid and/or lactic dehydrogenase (LDH) were also of prognostic significance, but predominantly reflected state, i.e., extent of disease. Age did not significantly influence prognosis. In the undifferentiated lymphoma subgroup, histology (i.e., Burkitt's lymphoma versus non-Burkitt’s lymphoma) was not of prognostic significance. Total white count was below 1,000/cu mm in 39% of cycles, and fever associated with granulocytopenia occurred in 17% of cycles. Stomatitis of moderate to severe extent occurred in 50% of cycles.(ABSTRACT TRUNCATED AT 400 WORDS)

Description: Evidence is presented that at least 17% of microscopically normal bone marrow samples obtained from patients with undifferentiated lymphomas contain occult tumor cells. Of 19 microscopically normal bone marrow samples tested, continuous tumor cell lines were obtained from 4. A tumor cell origin was confirmed by the presence of an 8;14 chromosomal translocation in each case, and HLA typing confirmed the patient origin of the cell line. In two other patients, direct cytogenetic examination of microscopically normal bone marrow samples revealed karyotypes containing 8:14 translocations or a 14q+ chromosome. These findings indicate that undifferentiated lymphomas are often more widespread than is clinically appreciated. The presence of submicroscopic marrow involvement is also of significance to the design and analysis of treatment protocols involving autologous marrow infusion.

Description: Intracellular lactate dehydrogenase (LD) isoenzyme patterns were studied in the malignant cells of patients with a variety of lymphoid malignancies. These were compared with intracellular LD isoenzyme patterns of normal lymphoid cells and were also correlated with immunologic cell surface marker characteristics. Results showed that, in general, the malignant B cells of Burkitt's lymphoma and the lymphoblasts of T-cell acute lymphoblastic leukemia had isoenzyme patterns similar to those of normal B and T cells, respectively. The isoenzyme patterns of malignant lymphoid cells from patients with non- T, and non-B acute lymphoblastic leukemia, cutaneous T-cell lymphoma, and chronic lymphocytic leukemia were more heterogeneous. These data, although based on small numbers of patients, are consistent with the hypothesis that LD isoenzymes may reflect differences in the maturational status of cells within a single diagnostic category.

Description: A particular translocation between chromosomes 8 and 14 has been found repeatedly in cytogenetic studies of Burkitt lymphoma, both of African and non-African origin. We report here our findings in cytogenetic studies of direct tumor preparations from 18 non-African Burkitt lymphoma patients, 9 of whom also had cell lines available for study. A t(8;14) was found in direct tumor material in 10 of the 18 patients. Seven of the 9 cell lines had a t(8;14). A total of 15 patients had either a t(8;14) or a 14q+ present in tumor material and/or cell lines. In addition, 8 patients had a peculiar marker chromosome 1. The t(8;14) was not found in every malignant cell and, where present, it was rarely the sole karyotypic abnormality. The relationship of the t(8;14) to the evolution of the tumor is discussed.

Description: Abstract 2395 While already tested in T-PLL, the impact of chemo-immunotherapy with alemtuzumab in combination with bi-weekly CHOP on autologous stem cell harvest (ASCH) has not yet been analysed in the context of first line treatment of primary systemic peripheral T-cell lymphoma (PTCL). We therefore evaluated the feasibility of ASCH in the first 23 patients of the ongoing international multicenter ACT-1 study, the first, and so far only, randomized trial in primary systemic PTCL. The ACT trials (ACT-1 + ACT-2) test the addition of alemtuzumab to CHOP followed, in younger patients (ACT-1), by high-dose therapy with autologous stem cell transplant (HDT+ASCT). The aims of the analysis were: (i) feasibility of ASCH in alemtuzumab + CHOP (A-CHOP) treated patients as compared to patients not receiving the antibody, but otherwise treated and managed in the same way, and (ii) comparison of ASCH counts in the two treatment arms. By July 2010, 20 patients, 11 in the standard treatment (arm A) and 9 in the experimental treatment (arm B) cohort, had undergone induction therapy and had been primed for subsequent ASCH according to local guidelines. Histological subtype distribution in the two treatment groups showed: PTCL not otherwise specified N=4 (arm A) and N=5 (arm B), angioimmunoblastic N=5 (arm A) and N=4 (arm B), extranodal NK/T-cell, nasal type N=1 (arm A), hepatosplenic N=1 (arm A). Pre-therapeutic evidence of bone marrow involvement was present in 4 (arm A) and 2 (arm B) patients, respectively. Of the original 23 patients, three did not undergo stem-cell harvest due to progressive disease (1 pt), patient's decision (1 pt), and pre-therapeutic CNS involvement (1 pt). Among the 20 harvested patients, ASCH failure was experienced in three patients (standard arm N=1 and experimental arm N=2; p=0.57). In two patients (one in each treatment cohort) a suboptimal stem cell yield could be optimized by the use of plerixafor according to local guidelines. A comparison of stem cell counts (CD34+ cells × 106/kg body weight) from the two treatment cohorts showed a trend towards moderately lower stem cell yields in alemtuzumab-treated patients (3.34 CD34+ cells × 106/kg body weight in arm B vs 6.54 CD34+ cells × 106/kg body weight in arm A, p=0.03). In conclusion, the addition of alemtuzumab to bi-weekly CHOP in the setting of first-line therapy of primary systemic PTCL does not significantly impair ASCH prior to upfront autologous stem cell transplant. Disclosures: No relevant conflicts of interest to declare.

Description: Recently we have observed an increased incidence of opportunistic infections in patients treated with intensive chemotherapy for cancer. Because T-cell depletion is associated with similar clinical events in human immunodeficiency virus infection and after bone marrow transplantation, we have analyzed peripheral blood lymphocyte populations in a series of patients during treatment with intensive chemotherapy for cancer. Although neutrophil, monocyte, and platelet numbers consistently recovered to greater than 50% of pretreatment values after each sequential cycle of therapy, lymphocyte numbers did not recover within the same time period. B cells decreased rapidly from a mean value of 149 +/- 46/mm3 before chemotherapy to 4 +/- 1/mm3 during chemotherapy (P = .01). CD4+ T cells decreased from a mean of 588 +/- 76/mm3 before chemotherapy to 105 +/- 28/mm3 during chemotherapy (P = .0002) and CD8+ T cells decreased from a mean of 382 +/- 41/mm3 before chemotherapy to 150 +/- 46/mm3 during chemotherapy (P = .0009). Natural killer cell numbers did not show significant declines (171 +/- 30/mm3 before, 114 +/- 24/mm3 during, P = .19). Based on the history of opportunistic complications in patients with other disorders who display similar degrees of CD4+ T-cell lymphopenia and preliminary observations in this population, immune incompetence could surface as a dose-limiting toxicity for highly dose-intensive chemotherapy regimens.