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Biomedical subjects

P McLaughlin

Publications and source records attributed to P McLaughlin.

At least 127 records · Page 7Linked to original sources
PubMed1993

New initiatives with fludarabine monophosphate in hematologic malignancies.

Fludarabine monophosphate (fludarabine) was initially discovered to have significant activity in indolent lymphoma and chronic lymphocytic leukemia (CLL). The major clinical experience with fludarabine is in previously treated patients with CLL. In such patients the complete and partial response rate (CR + PR) is over 50%. These results were obtained with 5-day schedules of fludarabine 25 to 30 mg/m2/d. Subsequent schedules have explored once-a-week fludarabine and a 3-day schedule every 4 weeks. These strategies, in particular the once-a-week schedule, have obtained inferior results. The addition of prednisone has not been associated with an improvement in response rate or survival. The application of fludarabine to previously untreated patients demonstrated a CR + PR rate of 75% to 80%. The addition of prednisone did not improve the response rate or survival in this group of patients. A significant concern in patients with CLL treated with fludarabine is a decrease in the CD4 and CD8 counts. Despite median posttreatment counts of approximately 200 CD4 lymphocytes/microL, the incidence of infections in patients in remission off therapy is low. Major clinical activity has been demonstrated with fludarabine in Waldenstrom's macroglobulinemia, in which more than one third of refractory patients achieve a CR or PR. Responding patients with anemia or thrombocytopenia have a marked improvement in blood counts. The duration of response has been long (> 30 months) in most responders. The early activity of fludarabine as a single agent in phase I/II studies in indolent lymphoma subsequently has been confirmed by a number of investigators. Fifty percent to 60% of patients with follicular lymphomas respond to fludarabine as a single agent. A number of these responses are complete despite the patients having received extensive prior treatment. A number of combination programs are being developed in CLL and indolent lymphoma. The combination of fludarabine with doxorubicin and prednisone has been developed and is being studied in phase I/II clinical trials. In addition, combinations of fludarabine and cytarabine with or without cisplatin based on elegant preclinical pharmacokinetic rationales have been applied to CLL with impressive cytoreductive activity but significant myelosuppression. A new combination of fludarabine, mitoxantrone, and dexamethasone has been developed for use in lymphoma. Phase I studies demonstrated a high response rate, especially in follicular lymphomas, with a number of patients achieving complete remission. Subsequent phase II studies demonstrate a response rate of 89% in patients with indolent lymphoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Antimetabolites, Antineoplastic↗
PubMed1993

A phase-I clinical study of low-dose oral interferon-alpha.

Twenty-five patients with systemic malignancies or cutaneous disorders were treated with low dosages (1-16 IU/kg/day) of oral interferon-alpha in a phase-I study. There were no grade-3 or -4 toxicities. No patients achieved a partial or complete response. One patient with renal cell carcinoma had prolonged disease stabilization lasting for 22 months. No significant changes in lymphocyte subsets including T4/T8 ratio, or serum immunoglobulins were observed. Subjective improvement in general well-being was reported by three patients. Low dosages of interferon-alpha administered orally do not appear to have any significant immunomodulatory or antitumor activity.

Administration, Oral↗
PubMed1992

Clinical, biologic, and histologic features of late relapses in diffuse large cell lymphoma.

After completing chemotherapy and achieving a complete remission (CR), patients with diffuse intermediate-grade lymphoma and immunoblastic lymphoma are usually considered cured if they are able to maintain that remission continuously for 24 months. Recently, we observed a number of patients with these disorders who relapsed after a continuous CR of greater than or equal to 30 months from the beginning of therapy or 24 months from completing chemotherapy. This finding led us to examine 503 consecutive cases to determine the risk of late relapse and their clinical and biologic features. We found that the overall risk of late relapse of those who attained CR was 6.8%, but several features at presentation were associated with a high risk: (1) the presence of a divergent histology; (2) a sclerosing large cell lymphoma; (3) a diagnosis based on an extranodal site with no nodal tissue available for examination. When none of these features were present, the risk of late relapse was minimal (only 3%). When any of these features was present, the risk was 14%. Most striking was the 43% late relapse rate of patients with divergent histology. All but one of the eight B-cell tumors studied at relapse showed kappa light chain restriction. Five of these eight has a low S phase at the time of relapse, suggesting chemotherapeutic selection of a clone of cells with a low proliferative potential that could have given rise to the late relapse. Nucleic acid flow cytometry and immunophenotypic studies on three tumors at initial diagnosis and after relapse failed to support the hypothesis of a second de novo lymphoma and were consistent with a true recurrence of the original tumor. The results of salvage chemotherapy in this group of late relapses showed a high CR rate (57%) but no evidence of a trend for cure in the time to treatment failure curve. In contrast to the experience with Hodgkin's disease, retreatment with the same or a similar regimen used for the original induction was not associated with durable response. Clinicians should be aware of the potential for a late relapse in cases with divergent histology and the need for new treatment strategies for such cases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Radiotherapy during pregnancy for clinical stages IA-IIA Hodgkin's disease.

Between 1956 and 1990, 775 women were treated for Hodgkin's disease at The University of Texas M.D. Anderson Cancer Center. Of these, 25 (3.2%) were pregnant at diagnosis. Seven of these women were in the first trimester, 10 in the second, and eight in the third. Prior to treatment, three women in the third trimester had normal deliveries, and six patients in the first trimester had abortions. Sixteen patients received radiotherapy for supradiaphragmatic presentations during their pregnancies. All these patients had nodular sclerosing Hodgkin's disease: Two had clinical stage IA presentations and 14 had clinical stage IIA. In two patients radiotherapy (35 Gy) was limited to the neck, three patients were treated definitively to the neck and mediastinum (40 Gy), and 11 patients received mantle irradiation (40 Gy). Four to five half-value layers of lead were used to shield the uterus during radiotherapy. The dose to the fetus was estimated individually in nine patients, using a combination of an Alderson-Rando and a water phantom. The estimated total dose to the mid-fetus ranged from 1.4 to 5.5 cGy for treatment with 6 MV photons, and from 10 to 13.6 cGy for Cobalt 60. All 16 patients subsequently delivered full-term, normal infants. Following delivery, all of the patients had further staging procedures; eight received additional treatment. Subsequently, the disease relapsed in four patients; two eventually died of Hodgkin's disease. The 10-year determinant and overall survival rates were 83% and 71%, respectively. Currently, all offspring are physically and mentally normal, and none has developed a malignancy. Radiotherapy is an appropriate initial treatment for supradiaphragmatic presentations of Hodgkin's disease during the second and third trimesters of pregnancy, provided special attention is paid to treatment and shielding techniques. The outcome for women treated with irradiation for clinical stage I and II Hodgkin's disease during pregnancy has not been shown to be adversely affected by pregnancy, and after the first 8 weeks of gestation, the risk to the fetus appears to be minimal.

Female↗
PubMed1992

NOVP and radiotherapy for early-staged Hodgkin's disease: an interim analysis.

Modern treatment plans for early staged Hodgkin's disease must focus on optimal disease-free survival results without laparotomy, minimal acute toxicity, and reduced long-term complications. We have treated 69 adult patients with stage I-II Hodgkin's disease, 40 of whom had bulky disease, B symptoms, or hilar disease, and 22 with stage III disease with 3 cycles of NOVP (Novantrone, vincristine, vinblastine, prednisone) and radiotherapy. Only patients with stage III1 disease involving the celiac axis without para-aortic or pelvic involvement, had to undergo laparotomy prior to treatment. Three patients did not respond to NOVP: two of these did not respond to MOPP or ABDIC, and two are currently without relapse following bone marrow transplant. With a median follow-up of 18 months, 62 with stage I-II and 19 with stage III remain without relapse, and 91 patients are alive. Tolerance to therapy was excellent with minimal nausea, myalgias, and alopecia. We conclude that this regimen for Hodgkin's disease provides good results for clinically staged I-III disease, but longer follow-up may demonstrate prognostic factors which will influence our results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Therapy of relapsed or refractory low-grade follicular lymphomas: factors associated with complete remission, survival and time to treatment failure.

Patients with relapsed low-grade follicular lymphomas (LGFL) frequently respond to subsequent therapy and can have long survival, but are rarely cured. Factors associated with complete remission (CR) rate, length of survival, and time to treatment failure (TTF) after relapse are not well known. We assessed such factors by multivariate analysis in a retrospective review of 95 patients with relapsed LGFL treated with investigational chemotherapy regimens at our institution. The CR rate after therapy was 22%; the likelihood of achieving CR was inversely associated with the number of previous treatment failures (P less than 0.001) and serum LDH level (P less than 0.05). Both the presence of constitutional symptoms and a history of more than two previous treatment failures were associated with shortened survival and TTF. Hemoglobin level was also significantly associated with survival. Prognostic models for survival and TTF were derived to define patient groups with different projected outcomes after therapy for relapsed disease. The results of this study can be used to select patients for new investigational treatments and to evaluate the outcome of such therapies.

Adult↗
PubMed1992

A proposal for a simple staging system for intermediate grade lymphoma and immunoblastic lymphoma based on the 'tumor score'.

A new staging system for intermediate grade lymphomas and immunoblastic lymphomas is described. This system is based on the tumor score which consists of assigning a point to each one of five variables that have been previously shown to have a high prognostic value. Ann Arbor stages III-IV, presence of bulky mass, elevation of B-2 microglobulin and LDH as well as presence of 'B' symptoms are the variables utilized in this system. When we applied this tumor score system to a population of 144 patients uniformly treated with CHOP/Bleo/CMED protocol, we observed that this system can accurately divide the population into two prognostic groups without an intermediate category. The first group is made up of those patients with a score of 0-2 points while the second group consists of patients with a score of > or = 3 points. The first group has a time-to-treatment failure (TTF) of 83% at three years in contrast to the second group whose TTF was 24%. If we compare this system with other commonly used systems in our institution, such as Ann Arbor, M.D. Anderson clinical staging system, and M.D. Anderson serological staging system, we observed that the tumor score system is not only more specific and sensitive than the others but also was capable of eliminating an intermediate risk group, thus facilitating therapeutic choices. This tumor score system is easy to apply and potentially reproducible in any institution.

Adolescent↗
PubMed1992

Case report: diagnosis of thyroid cancer by bone marrow biopsy in a patient with lymphoma and goiter.

Metastatic follicular thyroid carcinoma was diagnosed by bone marrow biopsy performed during the staging evaluation in a patient with large-cell lymphoma and diffuse goiter who showed lung and bone lesions upon radiologic examination. After thyroidectomy, both sites concentrated radioactive iodine, confirming their thyroid origin and allowing for the appropriate treatment.

Bone Marrow Diseases↗
PubMed1992

Phase II trial of fludarabine phosphate in lymphoma: an effective new agent in low-grade lymphoma.

PURPOSE: In a phase II trial we investigated fludarabine phosphate (FAMP) as therapy for patients with relapsed lymphoma to determine its effectiveness and toxicity in this disease. PATIENTS AND METHODS: The 67 assessable patients had a median age of 56 years and had received a median of three chemotherapy regimens before treatment with FAMP. The starting dose was 25 mg/m2 administered intravenously over 30 minutes daily for 5 days every 3 to 4 weeks. RESULTS: High response rates were observed for follicular small cleaved-cell lymphoma (FSCCL) (62%), follicular mixed small- and large-cell lymphoma (80%), and follicular large-cell lymphoma (FLCL) (100%). Responses also occurred in small lymphocytic lymphoma (SLL) (33%), transformed lymphoma (33%), mycosis fungoides (40%), and Hodgkin's disease (25%). No responses were observed in other intermediate- or high-grade lymphomas (N = 20). Overall, there were five patients with a complete response, 23 patients with a partial response, and an overall response rate of 37%. Toxicity was primarily hematologic and infectious. No significant gastrointestinal, hepatic, renal, or neurologic toxicity occurred. CONCLUSIONS: We conclude that FAMP has major activity in follicular lymphoma. Fundamental research is needed to understand this differential efficacy in low-grade lymphoma yet lack of efficacy in intermediate- and high-grade lymphoma. Clinical investigations should be done using FAMP in varying dose schedules and in combination regimens.

Adult↗
PubMed1992

Megavoltage grid total body irradiation of C3Hf/SED mice.

The effect of a grid on whole-body megavoltage radiation tolerance in C3Hf/SED mice was studied. Adult mice were irradiated beneath a 50% megavoltage grid. LD50 (50% lethality) values were measured at ten and 30 days. LD50/30 day increased by a factor of 1.5 for mice receiving both single and two fraction irradiation beneath the grid. LD50/ten day increased by factors of 1.1 to 1.2 for single, two, and five fraction irradiation beneath the grid.

Animals↗
PubMed1991

Prognostic value of serum beta-2 microglobulin in low-grade lymphoma.

OBJECTIVE: To evaluate serum beta-2 microglobulin (beta-2M) and other prognostic indicators in previously untreated low-grade lymphoma. DESIGN: Cohort study of 80 patients with uniformly treated low-grade lymphoma, followed for a median of 21 months. These 80 patients, all of whom had serum beta-2M drawn within 2 weeks before starting therapy, were derived from a cohort of 119 previously untreated patients entered into one of three clinical trials. SETTING: Tertiary referral cancer center. PATIENTS: Eighty previously untreated stage I to IV patients (mean age, 55 years). INTERVENTION: Treatment was given according to Ann Arbor stage: Patients in stage IV were treated with CHOP-bleomycin and maintained on interferon therapy; those in stage III received CHOP-bleomycin and radiotherapy; and those in stages I and II received COP-bleomycin and radiotherapy. MEASUREMENTS: Outcome was determined by assessing complete remission rate and time to treatment failure. Univariate and multivariate analyses were used. RESULTS: The complete remission rate for patients with a beta-2M level of 3.0 mg/L or greater was 36% compared with 71% for those with a level of less than 3.0 mg/L. Using multivariate analysis that tested beta-2M as a continuous variable, it was selected as the most significant factor for complete response. The adjusted odds ratio was 0.285 (95% CI, 0.101 to 0.809). The Ann Arbor stage had marginal significance (adjusted odds ratio, 0.435; CI, 0.150 to 1.263). For time to treatment failure, beta-2M was the only variable retained in the multivariate model. At 42 months, no patient with a beta-2M level of 3.0 mg/L or greater was projected to be in remission as compared with 85% of patients with a beta-2M level of less than 3.0 mg/L. CONCLUSIONS: The serum beta-2M level is a good predictor of complete response and time to treatment failure. A larger number of patients should be studied to clarify the role of other potentially independent variables such as stage and age.

Adult↗
PubMed1991

Stages I and II diffuse large cell lymphomas: prognostic factors and long-term results with CHOP-bleo and radiotherapy.

One hundred forty-seven patients with Ann Arbor stages I and II diffuse large cell lymphoma (DLCL) were treated with combination chemotherapy consisting of cyclophosphamide, doxyrubicin, prednisone, and low-dose bleomycin (CHOP-Bleo) and involved-field radiation (IF XRT) between 1974 and 1984. A complete remission (CR) was attained by 54 of 57 patients with stage I disease and by 78 of 90 patients with stage II disease. Thirty-five patients had relapsing disease that occurred within 3 years in 31. The overall 10-year survival rate, counting all deaths, for patients with stage I was 72% as compared with 43% for patients with stage II (P less than .01). Determinate survival rates, censoring eight unrelated deaths, were similar to the overall survival rates: 77% and 51%, respectively. A multivariate analysis identified three independent prognostic factors: age, tumor extent, and serum lactic dehydrogenase (LDH) level. When the combined effect of tumor extent and LDH level were taken into consideration in the analysis, three risk groups for survival were identified. The best group, which consists of patients with minimum tumor and normal LDH levels, had a 10-year determinate survival of 79%. Patients with extensive tumors and elevated LDH levels had the poorest survival rate of 44%. An intermediate-risk group with a determinant survival of 62% was composed of patients with either extensive tumors or elevated LDH levels. These differences demonstrate the need to develop different treatment strategies based on risk factors for survival for patients with apparently localized Ann Arbor stages I/II DLCL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Stage I-II low-grade lymphomas: a prospective trial of combination chemotherapy and radiotherapy.

Between 1984-1989, 44 patients with stage I-II low grade lymphoma were treated prospectively with sequential chemotherapy and involved-field radiotherapy. The chemotherapy was cyclophosphamide, vincristine, prednisone, and bleomycin (COP-Bleo); doxorubicin was included (CHOP-Bleo) for patients with adverse prognostic features (high LDH; extranodal sites; bulky nodes). Of the 44 patients, 37 had measurable disease and all have responded. With a median follow-up of 32 months, the 5-year survival and failure-free survival were 89% and 74%, respectively. Compared to past experience with involved-field radiotherapy alone, the failure-free survival is significantly better with COP-Bleo plus radiotherapy. The potentially cured fraction has risen from 40% to 74%.

Adult↗
PubMed1991

Two cycles of MOPP and radiotherapy: effective treatment for stage IIIA and IIIB Hodgkin's disease.

Two cycles of MOPP (mechlorethamine, vincristine (Oncovin), procarbazine, prednisone) and radiotherapy were used to treat 197 patients with stage III Hodgkin's disease. Prior to 1980, radiotherapy was delivered to the mantle, abdomen and pelvis; thereafter, pelvic irradiation was deleted for patients with stage III1 disease. Complete remission rates for IIIA and IIIB presentations were 91% and 89%. The 10-year freedom from tumor mortality (FTM) rate for all patients was 81%; for IIIA, it was 87% and for IIIB, it was 72%. Results were not significantly affected by gender, age, pathology, or deletion of pelvic radiotherapy. However, a subgroup of 28 patients with a tumor burden that included pelvic disease who also had B symptoms was identified as having a poor prognosis. Their FTM was 43%, compared with 87% for all other patients combined (P = 0.002). Based on this analysis, we conclude that limited chemotherapy in combination with radiation therapy can yield results similar to programs that use more chemotherapy for all patients with IIIA disease and for most patients with stage IIIB. However, patients with tumor burdens which include pelvic disease and B symptoms require a different approach.

Adult↗