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Biomedical subjects

A Mittelman

Publications and source records attributed to A Mittelman.

At least 73 records · Page 4Linked to original sources
PubMed1992

Homoharringtonine in combination with cytarabine for patients with acute myelogenous leukemia.

Homoharringtonine (HHT) is one of several cephalotaxine alkaloids that has shown clinical efficacy in patients with acute myelogenous leukemia (AML). In a phase I trial we evaluated cytarabine 100 mg/m2 by continuous infusion daily for 7 days in combination with four dose levels of HHT ranging from 1.5-5 mg/m2 by continuous infusion daily for 7 days to see if an effective regimen could be developed. Twenty-two patients with relapsed and/or primary refractory AML were treated. Seventeen males and five females were treated, with a median age of 40 years (range 19-63). There were five remissions in 14 patients with relapsed AML and none of eight responders in patients with primary refractory AML. None of the three patients treated at 1.5 mg/m2 dose level of HHT responded. Of three patients treated at the 3 mg/m2 dose level, there was one complete remission. At both 4 mg/m2 and 5 mg/m2, two of eight patients achieved complete remission. Four of the five remissions occurred in patients with acute promyelocytic leukemia. Drug induced pancytopenia was universal, and hypotension and fluid retention were more common at the higher dose levels. Other toxicity was mild and included nausea, vomiting, diarrhea, and mucositis. No significant hepatic, renal, or cardiac toxicity was seen. We conclude that the dose of HHT 4 mg/m2 for 7 days by continuous infusion in combination with cytarabine is safe for patients with AML; and this combination is appropriate for a phase II evaluation.

Adult↗
PubMed1992

Humoral antimelanoma immunity: induction by mouse antiidiotypic mAb, MK2-23 and association with survival of patients with advanced melanoma.

This study has shown that a mouse antiidiotypic mAb bearing a mirror image of HMW-MAA can break tolerance to a well-defined self HMW-MAA and can induce humoral anti HMW-MAA immunity in patients with melanoma. Furthermore, the induction of an immune response to a well-defined melanoma-associated antigen has been shown to be associated with a favorable clinical response. If this association reflects a cause-effect relationship between the two parameters, the anti HMW-MAA immunity induced by mouse antiidiotypic mAb MK2-23 may effect immune destruction of melanoma cells and may interfere with the metastatic potential of those cells because of the suggested role of HMW-MAA in this phenomenon.

Animals↗
PubMed1991

Leukemic dermal infiltrates at permanent indwelling central venous catheter insertion sites.

Three cases of leukemic dermal infiltrates at permanent indwelling central venous catheter insertion sites in patients with acute myelogenous leukemia are reported. Two patients had a localized soft tissue mass at the previous permanent indwelling catheter insertion site as the sole initial manifestation of relapse after achieving complete remission and undergoing bone marrow transplantation. The third patient had catheter tunnel sepsis preceding leukemic dermal infiltration. A review of the English language literature showed that this condition is rare with no specific pathogenetic mechanisms identified. Patients with unresolved catheter tunnel infections in acute leukemia and persistent chest wall masses that appear after a previous permanent indwelling catheter should have a biopsy done and be treated promptly.

Adult↗
PubMed1991

A phase II trial of interleukin-2 by continuous infusion and interferon by intramuscular injection in patients with renal cell carcinoma.

Fifteen patients with advanced, measurable renal cell carcinoma entered a Phase II clinical trial of interleukin-2 (IL-2) (Teceleukin, Hoffmann-La Roche Inc., Nutley, NJ) and interferon (IFN) (Roferon A, Hoffmann-La Roche Inc.). IL-2 was administered by continuous infusion daily for 4 days and IFN was administered by intramuscular injection daily for 4 days; therapy continued for 4 weeks. Eight men and seven women were treated in this trial (median age, 61 years). Toxicity was moderate to severe with fatigue, nausea, vomiting, hypotension, and elevated blood urea nitrogen bunion and creatinine levels seen in all patients. Two patients achieved a complete remission and two patients achieved a partial remission. The median duration of response was 18 months. IL-2 and IFN is an active combination in the treatment of renal cell carcinoma and warrants further investigation.

Adult↗
PubMed1991

Amsacrine is safe and effective therapy for patients with myocardial dysfunction and acute leukemia.

The role of amsacrine in inducing remission in patients with cardiac disease and acute leukemia was evaluated. There were 17 patients with acute myelogenous leukemia (AML), six with acute lymphocytic leukemia (ALL), and one with biphenotypic leukemia. In this series of 24 patients whose disease had relapsed and who had reduced left ventricular ejection fraction, nine had a complete remission, seven with AML and two with ALL. In addition, four of six with newly diagnosed acute leukemia and reduced left ventricular ejection fraction also responded. Among nine patients who underwent endomyocardial biopsy, none had morphologic changes of sufficient degree to account for drug-induced heart failure. Patients with preexisting arrhythmias received amsacrine without incident if their serum potassium level was higher than 4.0 mEq/l at the time of drug administration. Amsacrine is safe and effective therapy for patients with acute leukemia and cardiac disease.

Amsacrine↗
PubMed1991

Minimal toxicity during protein A immunoadsorption treatment of malignant disease: an outpatient therapy.

Extracorporeal removal or modulation of circulating immune complexes (CIC) from plasma of animals and humans with malignant disease may be associated with induction of immune-mediated anti-tumor responses. Immunoadsorption columns containing heat-killed and formalin-fixed Staphylococcus aureus or staphylococcal protein A have been used for this purpose but treatments have often been associated with cardiopulmonary toxicity. Recently, an immunoadsorption device containing highly purified protein A covalently attached to a silica matrix (PROSORBA column) was used to treat 142 patients with refractory malignancies and 22 of 104 patients evaluated for anti-tumor response had objectively measurable reduction in tumor burden. In contrast to earlier experience with other devices, the procedures used in this trial were well tolerated and could be performed on an outpatient basis. The most common side effects observed among 1,306 treatments were chills (28% of treatments), low grade fever (28%), and musculoskeletal pain (16%). Side effects were mild to moderate and required no treatment or only symptomatic treatment. Treatment schedules were interrupted due to side effects for only six patients and there were no treatment-related deaths. Of 64 patients available for long-term follow-up evaluation (mean of 11 months), none exhibited evidence of long-term treatment-related side effects. None of the patient deaths in that period were associated with short or long-term treatment-related side effects. Protein A-silica (PROSORBA columns) can be used safely for development of further experimental treatments of malignant disease.

Adolescent↗
PubMed1991

Use of protein A immunoadsorption as a treatment for thrombocytopenia in HIV-infected homosexual men: a retrospective evaluation of 37 cases.

Thirty-seven HIV-infected homosexual men with thrombocytopenia (less than 100 x 10(9)/l) received protein A immunoadsorption treatments to remove platelet-sensitizing immunoglobulin (Ig) G and circulating immune complexes (CIC) from plasma. Patients received an average of six treatments each, consisting of 250 ml plasma over a 3-week period. Clinical improvement in hemorrhagic symptoms associated with substantial increase in platelet counts was achieved in 18 patients. These responses were maintained over a median follow-up period of more than 7 months in 14 evaluable patients who were not lost to follow-up (three patients relapsed in 2 weeks and one received another therapy). Generally, moderate transient treatment-related side-effects included fever, musculoskeletal pain, chills and nausea. A transient serum sickness-like reaction was observed in seven patients, leading to termination of treatment in two. Clinical responses were associated with significant decreases in levels of platelet-sensitizing Ig, including CIC. Stimulation of broadly cross-reactive anti-antigen-binding fragment [F(ab)2], antibodies contributed to these responses. Protein A immunoadsorption is an effective alternative treatment for HIV-associated thrombocytopenia.

Adult↗
PubMed1991

Further thoughts on 'cell kill' in acute leukemia.

With traditional therapy of acute myelogenous leukemia, not more than 20% of patients achieve long-term survival. Efforts at intensifying postinduction chemotherapy have resulted in minor improvements only, but this limited progress has been hampered by increasing toxic-death rates. Eradication of the leukemia burden may be achieved by the introduction of more effective induction regimes and these may be rendered more effective by the application of 'enhancers'. With a lower tumor burden, and with more appropriate timing for supralethal therapy, it may be possible to achieve cure with greater frequency. Measurement of 'minimal residual disease' permits more logical selection of postinduction therapy.

Bone Marrow Transplantation↗
PubMed1991

Marrow storage techniques: a clinical comparison of refrigeration versus cryopreservation.

Fifty-three patients were evaluated for a comparison of the efficacy, safety, and cost efficiency of bone marrow (BM) transplanted after either refrigeration or cryopreservation. Thirty-eight patients had BM stored at 4 degrees C for an average of 3 days and 15 patients had cryopreserved BM stored for an average of 56 days. The average number of cells harvested was 3.8 x 10(8)/kg. The time to WBC recovery greater than 1 x 10(9)/l was 17 days refrigerated and 23 days for cryopreserved BM. The time to platelet recovery greater than 20 x 10(9)/l was 24 days for refrigeration storage and 51 days for cryopreserved BM. Four of 38 patients with refrigerated vs. 4/15 patients with cryopreserved BM experienced delayed engraftment (p less than 0.05). Refrigeration storage requires no special equipment, is cheaper than and presents a safe and viable alternative to cryopreserved BM in reconstituting hemopoiesis following high-dose chemo-radiotherapy.

Adolescent↗
PubMed1991

A loading dose/continuous infusion schedule of fludarabine phosphate in chronic lymphocytic leukemia.

Using a loading dose/continuous infusion schedule, fludarabine phosphate was administered to 51 patients with previously treated chronic lymphocytic leukemia (CLL). All patients had evidence of active disease, and the majority had advanced Rai stages. Of the 42 patients assessable for response, 22 (52%) achieved a partial response, five (12%) had stable disease, and 15 (36%) progressed. Thirteen of the 22 responders improved their Rai stages with fludarabine therapy, including six patients who achieved stage 0. Response rates for pretreatment stages III and IV were 60% and 53%, respectively. Patients with final Rai stages 0 to II had better survival than those with stages III and IV. Patients who had undergone splenectomy before starting therapy were more likely to respond. Myelosuppression was the primary toxicity and did not appear to be cumulative. Severe leukopenia and thrombocytopenia, although infrequent, were associated with several deaths in the early cycles of treatment. Nonhematologic toxicity was mild with no serious neurotoxicity noted. Infections were common with 22 minor, 18 major, and 10 fatal episodes. Fludarabine phosphate by this alternative dosing schedule is effective in refractory advanced CLL and is well tolerated by the majority of patients.

Adult↗
PubMed1991

Short course high dose mitoxantrone with high dose cytarabine is effective therapy for adult lymphoblastic leukemia.

Mitoxantrone is effective in the treatment of acute myelogenous leukemia and, in combination with either vincristine-prednisone or cytarabine (HiDAc), it is also effective in acute lymphoblastic leukemia (ALL). As mitoxantrone exhibits a steep dose-response curve against ovarian cancer cells and acute myeloid leukemia cells in vitro, we evaluated the safety and efficacy of high dose mitoxantrone with HiDAc in the treatment of ALL. Patients received mitoxantrone 20-37.5 mg/m2 daily for 2 days or 1 dose of 40-80 mg/m2 and HiDAc 3 g/m2 over 3 h once daily for five doses. All eight of the patients with previously untreated disease and eight of ten patients with ALL in relapse achieved complete remission (CR). The untreated patients included two with Philadelphia positive ALL who also achieved CR (one after one course of mitoxantrone-HiDAc, and one after one course of mitoxantrone-HiDAc followed by one additional dose of vincristine and daily prednisone). Seven of the eight previously untreated patients who achieved CR are still in remission. The one T-cell ALL has relapsed at 2 months after CR. The toxicity was acceptable. The regimen thus induces a remission rate equivalent to that of traditional vincristine-prednisone. The 'quality of remission' may be superior, and this therapy should be explored as a primary induction therapy in patients with ALL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

A phase I study of recombinant human interleukin-2 and alpha-interferon-2a in patients with renal cell cancer, colorectal cancer, and malignant melanoma.

Preclinical data suggest synergy of interleukin-2 (IL-2) combined with alpha-interferon (IFN). In addition, toxicities of IL-2 may be decreased by intermittent continuous infusion. The purpose of this trial was to determine the maximum tolerated dose (MTD) of recombinant IL-2 combined with alpha-IFN in patients with renal cancer, colon cancer, melanoma, and malignant B-cell disease. IL-2 was given by continuous i.v. infusion at an initial dose of 5 X 10(5) units (U)/m2/d for 4 days plus IFN at 6 X 10(6) U/m2/d intramuscularly days 1 and 4 weekly for 4 weeks. Patients who achieved a response or stable disease received an additional 4 weeks of therapy. IL-2 doses were increased to 1, 2, 3, 5, and 7 X 10(6) U/m2/d with three to eight patients at each dose level, at each of the two participating institutions. The dose of IFN was 6 X 10(6) U/m2 days 1 and 4 for all but five patients whose IFN dose was doubled to 12 X 10(6) U/m2/d. Forty-three patients were entered on this study with 34 completing at least 4 weeks of therapy. Six patients were taken off study because of Grades III or IV pulmonary, neurologic, or cardiac toxicity; one for progressive disease; one for CNS metastases, and one for personal reasons. All of the toxicities were reversible. Chills and fever were universal, especially on days 1 and 4. Mild and moderate nausea, vomiting, diarrhea, anorexia, malaise, and cutaneous erythema were present in most patients. Fluid retention and occasional pleural effusions were observed at the higher IL-2 doses but were not dose-limiting. Significant hypotension associated with oliguria was seen, and these patients were treated with vasopressors and colloids. None of the patients required ICU admission. Thirty-four patients were evaluable for response. There were 4/18 (22%) renal cell patients who experienced a partial response. No responses were seen in patients with melanoma, lymphoma, or colorectal cancer. The combined debilitating symptoms of fatigue, diarrhea, hypotension, fluid retention, and anorexia defined the MTD as 5 X 10(6) U/m2/d of IL-2 and 6 X 10(6) U/m2 of alpha-IFN.

Adult↗
PubMed1990

Phase II trial of fludarabine phosphate (F-Ara-AMP) in patients with advanced head and neck cancer.

Thirteen patients with advanced head and neck cancer were entered into a phase II study of fludarabine phosphate. Fludarabine phosphate was given by continuous infusion for 5 days, at a starting dose of 20 mg/m2 per day for patients previously treated with one regimen and 25 mg/m2 per day for previously untreated patients; therapy was repeated every 3-4 weeks. Of the 13 patients, 3 had undergone one prior regimen and 10 patients were previously untreated by chemotherapy. No responses were observed. Myelosuppression was the most common toxicity observed. Four patients developed mild nausea, vomiting and seven developed bleeding stomatitis that resolved in one week. In addition, four patients developed headaches which resolved spontaneously. No renal, hepatic, or neurotoxicity was observed. Our study demonstrates that in previously treated and untreated patients, fludarabine phosphate given on this schedule has little activity in patients with advanced head and neck cancer.

Aged↗
PubMed1990

Active specific immunotherapy in patients with melanoma. A clinical trial with mouse antiidiotypic monoclonal antibodies elicited with syngeneic anti-high-molecular-weight-melanoma-associated antigen monoclonal antibodies.

In two clinical trials the mouse antiidiotypic monoclonal antibody (MAb) MF11-30, which bears the internal image of human high-molecular-weight-melanoma-associated antigen (HMW-MAA) was administered by subcutaneous route without adjuvants to patients with stage IV malignant melanoma on day 0, 7, and 28. Additional injections were administered if anti-antiidiotypic antibodies were not found or their titer decreased. In the first phase I trial with 16 patients the initial dose was 0.5 mg per injection and escalated to 4 mg per injection. Neither toxicity nor allergic reactions were observed despite the development of anti-mouse Ig antibodies. Minor responses were observed in three patients. In a second clinical trial MAb MF11-30 was administered to 21 patients at a dose of 2 mg per injection, since this dose had been shown in the initial study to be effective in inducing anti-antiidiotypic antibodies. Two patients were inevaluable; in the remaining 19 patients, the average duration of treatment was 34 wk. In this trial as well, neither toxicity nor allergic reactions were observed. 17 of the 19 immunized patients increased the levels of anti-mouse Ig antibodies and 16 developed antibodies that inhibit the binding of antiidiotypic MAb MF11-30 to the immunizing anti-HMW-MAA MAb 225.28. One patient increased the level of anti-HMW-MAA antibodies. One patient achieved a complete remission with disappearance of multiple abdominal lymph nodes for a duration of 95 wk. Minor responses were observed in three patients. These results suggest that mouse antiidiotypic MAb that bear the internal image of HMW-MAA may be useful reagents to implement active specific immunotherapy in patients with melanoma.

Adult↗