Arlan J. Gottlieb

Chemotherapy of Advanced Hodgkin's Disease with MOPP, ABVD, or MOPP Alternating with ABVD

BACKGROUND AND METHODS MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) has been the standard treatment for Hodgkins disease for almost 20 years. In a randomized, multicenter trial, we compared three regimens of primary systemic therapy for newly diagnosed advanced Hodgkins disease in Stages IIIA2, IIIB, and IVA or IVB: (1) MOPP alone given for 6 to 8 cycles, (2) MOPP alternating with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for 12 cycles, and (3) ABVD alone for 6 to 8 cycles. Patients in a first relapse after radiation therapy were eligible. No additional radiation therapy was given. Patients who did not have a complete response or who had a relapse with either MOPP alone or ABVD alone were switched to the opposite regimen. RESULTS Of 361 eligible patients, 123 received MOPP, 123 received MOPP alternating with ABVD, and 115 received ABVD alone. The patients were stratified according to age, stage, previous radiation, histologic features, and performance status. The overall response rate was 93 percent, with complete responses in 77 percent: 67 percent in the MOPP group, 82 percent in the ABVD group, and 83 percent in the MOPP-ABVD group (P = 0.006 for the comparison of MOPP with the other two regimens, both of which contained doxorubicin). The rates of failure-free survival at five years were 50 percent for MOPP, 61 percent for ABVD, and 65 percent for MOPP-ABVD. Age, stage (III vs. IV), and regimen influenced failure-free survival significantly. Overall survival at five years was 66 percent for MOPP, 73 percent for ABVD, and 75 percent for MOPP-ABVD (P = 0.28 for the comparison of MOPP with the doxorubicin regimens). MOPP had more severe toxic effects on bone marrow than ABVD and was associated with greater reductions in the prescribed dose. CONCLUSIONS In this trial, ABVD therapy for 6 to 8 months was as effective as 12 months of MOPP alternating with ABVD, and both were superior to MOPP alone in the treatment of advanced Hodgkins disease. ABVD was less myelotoxic than MOPP or ABVD alternating with MOPP.

Adult idiopathic thrombocytopenic purpura: Clinical findings and response to therapy

Abstract Sixty-two adults with idiopathic thrombocytopenic purpura were seen from 1971 to 1979. All were >16 years old, with 150,000/μl). In 75 percent of the patients, complete remission was achieved by six weeks. Only 29 percent of those with a complete remission (complete responders) are projected to be in a continuing remission after 48 months. The majority of relapses occurred during the first two years of remission. A symptom duration of

Red-Cell 2,3-Diphosphoglycerate Levels in Subjects with Chronic Hypoxemia

Recently, Benesch et al.1 , 2 and Chanutin and Curnish3 demonstrated that the affinity of a hemoglobin solution for oxygen may be decreased by its interaction with organic phosphates. Both 2,3-diph...

The effects of deoxygenation of adult and fetal hemoglobin on the synthesis of red cell 2,3-diphosphoglycerate and its in vivo consequences

Patients over 1 month of age with arterial oxygen pressures of less than 60 mm Hg were found to have elevated red cell 2,3-diphosphoglycerate (2,3-DPG) levels and blood with a decreased affinity for oxygen. The increase in 2,3-DPG was proportional to the degree of hypoxemia. In patients under 1 month of age this relationship was not observed. Red cells from adults, but not newborns, showed rapid increases in 2,3-DPG when incubated under nitrogen. Adult, but not fetal, deoxyhemoglobin was shown to facilitate in vitro synthesis of 2,3-DPG by binding this organic phosphate and relieving the product inhibition of 2,3-DPG mutase. Throughout a wide range change in oxygen affinity as measured by the P(50) is linear with respect to the 2,3-DPG concentration; a change of 430 mmumoles of 2,3-DPG/ml of red blood corpuscles (RBC) resulting in a change of the P(50) of 1 mm Hg. It appears that the 2,3-DPG of the adults red cells responds rapidly to metabolic and environmental influences and in turn effects metabolism and the cellular environment. Many of these effects are not shared by the red cells of the newborn.

The Immunophenotyping of Extramedullary Myeloid Cell Tumors in Paraffin-embedded Tissue Sections

Extramedullary tissue infiltrates of acute myeloid leukemia are rare and often difficult to recognize in routine paraffin-embedded tissue sections. Since appropriate therapy for these tumors depends on their precise identification, we have studied a series of tissues infiltrated with primitive myeloid cells using monoclonal and polyclonal antibodies capable of labeling cells of the myeloid/monocytic system in paraffin-embedded tissue sections. The current retrospective study involved tissues from 15 patients (eight men and seven women) with a mean age of 51 years (range, 23–77). A diagnosis of extramedullary myeloid cell tumors had been made on the basis of routine histology, chloroacetate esterase cytochemical stain, and—in some cases—electron microscopy. Paraffin-embedded tissue sections were cut and stained employing the alkaline phosphatase antialkaline phosphatase (APAAP) immunocytochemical procedure with monoclonal antibodies against leukocyte-common antigen (PD7/26–2B11), restricted components of the leukocytecommon antigen (UCHL1, 4KB5), granulocytes (Mac-387, Leu-M1), leukocytes (MT1, MT2, LN1, LN2), HLA-DR (LN3), and elastase (NP57), as well as polyclonal antibodies against lactoferrin, lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin. Results indicate that antibodies against Mac-387, elastase, and lysozyme are most useful in the recognition of neoplastic myeloid cells. We conclude that tissues containing granulocytic tumors can be identified in paraffin-embedded tissue sections using a panel of antibodies and the APAAP procedure.

Relationship between plasma adriamycin levels and the outcome of remission induction therapy for acute nonlymphocytic leukemia

SummaryPlasma adriamycin and adriamycinol levels were masured in 45 patients with acute nonlymphocytic leukemia 3 h after the drug was administered. A wide range of levels was found. Plasma levels increased after the administration of each of three daily doses of the drug. High plasma levels were associated with both death during remission induction therapy and, for patients who entered remission, long remissions.

Postsurgical adjuvant chemotherapy of stage II breast carcinoma with or without crossover to a non-cross-resistant regimen: a Cancer and Leukemia Group B study.

PURPOSE To compare two cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) regimens with a doxorubicin-based regimen--vinblastine, doxorubicin, thiotepa, and Halotestin (Upjohn, Kalamazoo, MI) (VATH)--in patients with stage II node-positive breast carcinoma. METHODS Nine hundred forty-five women were treated with a 6-week induction course of CMFVP. They were then randomized to receive one of two consolidation CMFVP regimens: 6-week courses or 2-week courses. Following completion of CMFVP consolidation, patients were again randomized to either continue the CMFVP regimen or to receive six escalating doses of VATH. RESULTS Among all patients, with a median follow-up time of 11.5 years, there is no statistically significant difference in disease-free survival (DFS) between the two consolidation CMFVP regimens. VATH intensification treatment is statistically significantly superior to CMFVP in terms of DFS (P = .0040). For patients with one to three involved nodes, there is currently no significant difference between VATH and CMFVP; however, among those with four or more positive lymph nodes, there is a significant difference in favor of VATH (P = .0037). There is also improved overall survival with VATH (P = .043; median, > 14 years v 10 years). This difference is also statistically significant in patients with four or more involved lymph nodes, among postmenopausal patients, and among postmenopausal estrogen receptor-positive patients. CONCLUSION Chemotherapy with crossover to escalating doses of VATH following CMFVP was well tolerated and effective. Inauguration of VATH as a treatment intensification at the eighth month produced a major increase in relapse-free and overall survival. The observation that sensitivity to VATH is retained so long after mastectomy raises questions about the proper duration of adjuvant chemotherapy and lends support to further investigation of cross-over designs in future trials to postoperative adjuvant chemotherapy regimens.

Immunophenotypic subclassification of chronic lymphocytic leukaemia (CLL)

To determine the significance of the immunophenotypic heterogeneity of B‐cell chronic lymphocytic leukaemia (CLL), surface immunoglobulins (SIgs), mouse rosette assays (MR), and a panel of monoclonal antibodies for B cells, T cells and myeloid cells were performed on peripheral blood samples from 61 newly diagnosed cases. Four groups were observed: group I (SIg+, MR+, CD19/20+, CD5+, T antigen (Ag)‐; 27 cases); group II (SIg+, MR+, CD19/20+, CD5+, T Ag+; 17 cases); group III (SIg+, MR+ CD19/20+, CD5‐, T AG‐; 12 cases); and group IV (SIg‐, MR+, CD19/20+, Cd5+, T Ag‐; 5 cases). Groups were compared according to French–American–British Cooperative Group subtypes, clinical and laboratory features, Rai staging, and survival. Typical CLL morphology (>90% small lymphocytes) was present in 20/20 (100%) of group I cases and 23/27 (85%) group II, III and IV cases (P=0·09). Expression of a myeloid antigen was seen in 5/27 group I cases (18%) and 1/16 group II cases (6%), but was not predictive of survival (P=0·36). The CD5‐ group III had a lower haemoglobin level (P<0·0001), higher Rai stage (P<0·002), and poorer survival at 5 years (P<0·02) than the other groups. We conclude that at least four distinct immunophenotypic subgroups of B‐cell CLL can be determined. Expression of myeloid or T‐cell antigens does not appear to predict for patient survival: however, lack of CD5 antigen may be associated with more advanced stage of disease and poor patient survival.

Case Report Idiopathic thrombocytopenic purpura and Hodgkin’s disease: report of two cases and a review of the literature

Abstract Twenty-five patients from the literature and two additional patients with Hodgkin’s disease and idiopathic thrombocytopenic purpura (ITP) are reviewed. In 22 patients the ITP occurred after the Hodgkin’s disease was treated. In nine of these patients, the Hodgkin’s disease was active at the time of the ITP. In four patients, the diagnosis of ITP was concurrent with that of Hodgkin’s disease. In one patient, ITP preceded Hodgkin’s disease by one year. Seven of 26 patients achieved complete remission of the ITP with prednisone. In each of these patients the Hodgkin’s disease was in complete remission, and each had a previous splenectomy. Seven of 14 patients achieved complete remission of the ITP after splenectomy. Four of these patients had active Hodgkin’s disease. Of the 27 patients, 14 were in remission of the Hodgkin’s disease at the time of ITP. To date, relapse of the Hodgkin’s disease has occurred in only one patient. Lymphadenopathy in five of these patients proved to be benign hyperplasia on biopsy. In addition to the association with Hodgkin’s disease, review of ITP cases at Upstate Medical Center and a recent report in the literature indicate that there may be a general association between ITP and malignancy.

Prediction of response of patients with acute nonlymphocytic leukaemia to remission induction therapy: use of clinical measurements

Two hundred patients with acute nonlymphocytic leukaemia received remission induction therapy consisting of cytosine arabinoside and an anthracycline antibiotic. Analysis of the pretherapy characteristics of the patients demonstrated that patient age was the most important factor in determining whether or not the patient would survive remission induction therapy. Assessment of the characteristics of the bone marrow after 6 d of therapy permitted the recognition of patients who were likely to fail to enter remission because of persistent leukaemia. Taken together, these observations demonstrate that it is possible to identify patients for whom conventional chemotherapy is not likely to be of benefit either because it is too intensive or because it is not intensive enough to produce a complete remission.