Letha Mills - Academia.edu (original) (raw)

Papers by Letha Mills

Annals of Neurology, 1978

Blood, Feb 1, 1985

Information about reproducing this article in parts or in its entirety may be found online at:

Jama the Journal of the American Medical Association, Nov 21, 1986

... Re¬ cent reports suggest that the combina¬ tion of parenteral clindamycin and oral quinine er... more ... Re¬ cent reports suggest that the combina¬ tion of parenteral clindamycin and oral quinine eradicates B microti infection even in immunosuppressed patients with ... 3. Jacoby GA, Hunt JV, Kosinski KS, et al: Treatment of transfusion-transmitted babesiosis by exchange transfusion ...

Annals of Internal Medicine, Nov 1, 1983

Two patients had a previously unrecognized form of crystallocryoglobulinemia. Their clinical pres... more Two patients had a previously unrecognized form of crystallocryoglobulinemia. Their clinical presentations were similar, consisting of necrotizing vasculitis and purpura involving the legs. Analysis of each cryoglobulin complex showed that two components, albumin and a monoclonal IgG-lambda, were present, and both components were needed in a fixed ratio for precipitation. In addition, cryoprecipitation occurred in serum, but not plasma, due to citrate inhibition of complex formation. Our findings suggest that the monoclonal IgGs have the properties of antibodies directed specifically against a calcium-dependent antigenic site on human albumin, and that the resultant IgG-lambda-albumin immune complexes crystallized in the cold.

The high-affinity receptor for the constant region of immunoglobulin G IgG (Fc-yRI; CD64) is virt... more The high-affinity receptor for the constant region of immunoglobulin G IgG (Fc-yRI; CD64) is virtu- ally undetectable on mature polymorphonuclear neutro- phils (PMNs) in healthy individuals but is expressed on PMNs in patients with certain infections and in patients treated with recombinant human granulocyte colony- stimulating factor (rhG-CSF). The induction of FcyRI by rhG-CSF has previously been reported to result

Blood, Jan 15, 1994

We have conducted a 9-year multicenter trial of autologous bone marrow transplantation (ABMT) for... more We have conducted a 9-year multicenter trial of autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML). Remission BM was purged in vitro using monoclonal antibodies (MoAbs; PM-81, AML-2-23) and complement targeting myeloid differentiation antigens (CD15, CD14). In 1988, the preparative regimen changed from 60 mg/kg/d cyclophosphamide x 2 and fractionated total body irradiation (TBI) total dose, 1,200 cGy (Cy/fTBI), to 4 mg/kg/d busulfan x 4 and 60 mg/kg/d Cy x 2 (Bu/Cy2). Recent analysis (October 1, 1993) shows that the Bu/Cy2 regimen along with the same MoAb purging method yields an improved outcome. Seven first complete-remission (CR) (CR1), 45 second- or third-CR (CR2/3), and 11 first-relapse (R1) patients were treated with chemotherapy and TBI or chemotherapy alone followed by ABMT with MoAb-purged BM. Median age at ABMT for those patients in CR 2/3 and R1 patients was 36 years. Twenty-nine CR 2/3 and R1 patients were conditioned with Cy/fTBI, and 27 CR2/...

The Journal of Dermatologic Surgery and Oncology, 1987

Halo cutaneous melanoma developed in a 30-year-old woman. Following wide excision of the melanoma... more Halo cutaneous melanoma developed in a 30-year-old woman. Following wide excision of the melanoma, she remained clinically free of tumor for 5 years. In a subsequent pregnancy, she developed metastases to the liver which became evident in the immediate postpartum period. Long-term survival associated with cutaneous hypopigmentation has been reported and occurred in our patient. The interaction between hormonal and immunologic factors and melanoma is explored.

Journal of Hematotherapy, 1992

The high-affinity receptor for IgG, Fc gamma RI, expressed on monocytes and interferon-gamma (IFN... more The high-affinity receptor for IgG, Fc gamma RI, expressed on monocytes and interferon-gamma (IFN-gamma)-stimulated neutrophils, is a trigger molecule for cell-mediated cytotoxicity. We have prepared murine monoclonal antibodies (MoAb 22 and MoAb 32) that bind to Fc gamma RI outside the ligand binding site and thus bind to and trigger cytotoxicity that is not competed by other immunoglobulins. Because of these properties, it seemed that these MoAbs would be very useful for the development of bispecific antibodies (BsAb) for targeting normal cellular immune defense mechanisms as a new form of immunotherapy for treatment of cancer. BsAbs incorporate into a single molecule the binding specifities of two different antibodies, and, thus, can be used to target myeloid cells to tumors, ensure activation of cellular cytotoxic mechanisms, and target cell lysis and/or phagocytosis. BsAbs were prepared using anti-Fc gamma RI MoAb and an anti-myeloid cell MoAb, PM81, reactive with the CD15 antigen, for studies of antibody-dependent cellular cytotoxicity. Conjugates were made by cross-linking sulfhydryl groups of Fab fragments of MoAb 32 or 22 (both IgG1) and sulfhydryl groups added to intact PM81 (an IgM) using N-succinimdyl-acetyl-S-thioacetate (SATA). The resulting product was purified by high-performance size-exclusion chromatography. The ability of the BsAbs to mediate attachment of human monocytes to tumor target cells was confirmed in a microtiter well assay of binding of MTT-labeled U937 cells (a human Fc gamma RI-bearing cell line) to SKBR-3 (PM81-reactive breast carcinoma) target cells. The ability of the BsAbs to mediate killing of HL-60 promyelocytic leukemia cells was studied using a 6-hour Chromium-51 release assay. Effector cells were monocytes obtained by cytopheresis and cultured for 18 hours with IFN-gamma. Monocytes alone caused minimal killing (5-20%), monocytes plus BsAb caused moderate killing (20-50%), and monocytes plus BsAb plus human serum resulted in maximal killing (50-80%). Experiments were performed to test the ability of the BsAb to purge bone marrow of small numbers of leukemia cells using bone marrow mononuclear phagocytes treated for 18 hours with IFN-gamma prior to adding target cells. Without the addition of human serum as a source of complement, a 90% depletion of clonogenic HL-60 cells could be demonstrated. With human complement, up to 95% depletion was seen. Thus, this BsAb possessed the ability to lyse tumor cell targets by two different mechanisms, complement and cell-mediated lysis.(ABSTRACT TRUNCATED AT 400 WORDS)

$Research paper thumbnail of Mitoxantrone in relapsed or refractory acute nonlymphocytic leukemia$

Medical and Pediatric Oncology, 1988

Seventeen patients with relapsed or refractory acute nonlymphocytic leukemia were treated with 14... more Seventeen patients with relapsed or refractory acute nonlymphocytic leukemia were treated with 14 mg/m2 of mitoxantrone given in a 30-minute infusion daily for three days. If the day fourteen bone marrow showed residual leukemia, a second course was given at the same dose for two days. Eight patients (47%) entered complete remission. Three patients (17%) had a partial response, four (24%) did not respond, and two (12%) died with hypoplastic marrows during treatment. Seven of the 12 relapsed patients entered a complete remission, as did one of the five refractory patients. Toxicity was acceptable; prolonged myelosuppression, moderate hepatic toxicity, and stomatitis were the only problems. Several dose schedules of mitoxantrone have been studied by other investigators with varying results. The three-day schedule in the present study is similar to the schedule used for common induction regimens employing anthracycline drugs. On the basis of its activity and acceptable toxicity in relapsed and refractory ANLL patients, we feel that this schedule could be safely combined with other agents in future studies.

JAMA: The Journal of the American Medical Association, 1986

Cancer Investigation, 1990

Cancer Genetics and Cytogenetics, 1991

Cytogenetic analysis was performed on the histologically and immunophenotypically normal bone mar... more Cytogenetic analysis was performed on the histologically and immunophenotypically normal bone marrow (BM) of a 33-year-old woman with non-Hodgkin's lymphoma (NHL) before BM harvest. Unstimulated 24- and 48-hour cultures produced only normal metaphases. A pokeweed mitogen (PWM)-stimulated 48-hour culture, however, showed a clonal isodicentric chromosome 18q as the sole abnormality, suggesting a role for this approach in detection of submicroscopic BM involvement by B-cell NHL.

Cancer, 1996

Based on previous data demonstrating a potentially synergistic interaction between tamoxifen and ... more Based on previous data demonstrating a potentially synergistic interaction between tamoxifen and cisplatin in metastatic melanoma therapy, a Phase II study was performed to assess the activity of tamoxifen, etoposide, mitoxantrone, and cisplatin (TEMP) in patients with metastatic breast carcinoma. Forty-six patients with metastatic breast carcinoma were treated with tamoxifen, 10 mg orally, twice a day for 28 days; etoposide, 100 mg/m2, on Days 1-3; mitoxantrone, 10 mg/m2, on Day 1; and cisplatin, 30 mg/m2, on Days 1 and 2. Forty-four patients (7 with bone only disease) were evaluable for response and toxicity after at least 1 cycle of therapy. All patients had previously received doxorubicin-containing regimens in either the adjuvant or metastatic setting. The overall objective response rate for the 37 patients with visceral and/ or soft tissue disease was 41% (95% confidence interval, 25-58%). The objective response rate among women previously treated with doxorubicin in the adjuvant setting was 56% (14 of 24). Only 1 of 13 patients with metastatic carcinoma who had failed doxorubicin responded. Five of seven patients with bone-only disease had subjective improvement of bone pain without worsening of bone scans. Approximately 59% of patients had Grade 3 or 4 neutropenia at some time in their therapy and 1 patient died of neuropenic sepsis. Logistic regression analysis (n = 37) revealed that response was not related to estrogen receptor (ER) status or to the presence of visceral metastases. TEMP appears to be an active regimen for patients with either ER positive (tamoxifen-resistant) or ER negative metastatic breast carcinoma that progresses after adjuvant doxorubicin therapy. Moreover, among patients who developed metastatic disease either during or < 12 months after adjuvant doxorubicin therapy, TEMP had a higher response rate than would have been predicted from previous studies. Although the mechanism remains to be elucidated, these results suggest a potentially synergistic role for tamoxifen in etoposide/cisplatin-based chemotherapy of breast carcinoma.

Annals of Internal Medicine, 1983

American Journal of Hematology, 1989

Flow cytometric reticulocyte quantification with thiazole orange (TO) was used to study erythropo... more Flow cytometric reticulocyte quantification with thiazole orange (TO) was used to study erythropoiesis in 20 patients following autologous bone marrow transplantation for the treatment of acute myelogenous leukemia. Flow cytometric reticulocyte analysis provided not only the reticulocyte percentage and absolute reticulocyte count but a quantitative reticulocyte maturity index (RMI) proportional to the amount of RNA in the reticulocytes. The RMI values, but not the reticulocyte percentage or absolute counts, correlated temporally with the rise in the absolute neutrophil counts in the posttransplantation period. In the majority of patients (12/20), the RMI value was the earliest indicator of bone marrow engraftment. The findings of this study demonstrate an important clinical utility of TO reticulocyte analysis by flow cytometry and indicate the diagnostic importance of the RMI measurement in the evaluation of erythropoietic activity in bone marrow transplant patients.

American Journal of Hematology, 1994

The development of spontaneously acquired Factor VIII inhibitors is rare and may lead to serious ... more The development of spontaneously acquired Factor VIII inhibitors is rare and may lead to serious hemorrhagic sequeiae. We report here the case of a patient who acquired a Factor Vlll inhibitor two years after an allogeneic bone marrow transplant for CML. This occurred in association with a flare of chronic graft versus host dlsease (GVDH). He responded to corticosteroid therapy. A review of autoimmune phenomena associated with chronic GVDH and the treatment of Factor Vlll Inhibitors is discussed.

Journal of Pain and Symptom Management, 1999

The purpose of the current study was to examine the impact of massage therapy on psychological, p... more The purpose of the current study was to examine the impact of massage therapy on psychological, physical, and psychophysiological measures in patients undergoing autologous bone marrow transplantation (BMT). Patients scheduled to undergo BMT were randomly assigned to receive either (a) massage therapy, consisting of 20-minute sessions of shoulder, neck, head, and facial massage, or (b) standard treatment. Overall effects of massage therapy on anxiety, depression, and mood were assessed pretreatment, midtreatment, and prior to discharge using the State-Trait Anxiety Inventory, Beck Depression Inventory, and Brief Profile of Mood States, respectively. The immediate effects of massage were measured via the State Anxiety Inventory, Numerical Scales of Distress, Fatigue, Nausea, and Pain and indices of psychophysiological arousal (heart rate, blood pressure, and respiration rate), collected prior to and following patients' first, fifth, and final massage (on Days Ϫ 7, midtreatment, and predischarge). Analysis of the data evaluating the immediate effects of massage showed that patients in the massage therapy group demonstrated significantly larger reductions in distress, fatigue, nausea, and State Anxiety than the standard treatment group at Day Ϫ 7, in State Anxiety at midtreatment, and in fatigue at the predischarge assessment. The overall measures of psychological symptoms measured at pretreatment, midtreatment, and prior to discharge showed no overall group differences, although the massage group scored significantly lower on the State Anxiety Inventory than the standard care group at the midtreatment assessment. The two groups together showed significant declines through time on scores from the Profile of Mood States and State and Trait Anxiety Inventories.