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Biomedical subjects

P Mauch

Publications and source records attributed to P Mauch.

At least 109 records · Page 6Linked to original sources

Wide-field radiation therapy alone or with chemotherapy for Hodgkin's disease in relapse from combination chemotherapy.

Nineteen patients with Hodgkin's disease who relapsed primarily in nodal sites after intensive combination chemotherapy were retreated with wide-field radiation therapy alone or with additional chemotherapy between January 1971 and December 1984. Six patients presented in second relapse and 13 patients in first relapse. Seven patients were treated with combination chemotherapy and radiation therapy and twelve patients were treated with radiation therapy alone. Radiation therapy field sizes and doses were similar to those recommended for early-stage Hodgkin's disease patients treated with radiation therapy alone. The 5-year actuarial freedom from relapse (FFR) and survival following retreatment were 48% and 69%, respectively. Twelve patients are currently disease-free 12 to 172 months following retreatment. Wide-field radiation therapy alone or with additional chemotherapy should be considered for patients with advanced Hodgkin's disease who relapse in nodal sites after initial combination chemotherapy.

Actuarial Analysis↗

Biochemical genetics of TL antigens.

TL antigens are class I glycoproteins which are expressed on thymocytes and which are coded by the Tla region of the major histocompatibility complex of the mouse. Biochemical analysis of TL molecules from different strains of mice revealed structural variation determined by the Tla region which is detectable by peptide mapping, isoelectric focusing, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, two-dimensional gels, and by differential reactivity of allelic forms of TL molecules with a panel of anti-TL reagents. The quantity of TL expressed on thymocytes is also influenced by the Tla region; three quantitative phenotypes were identified: high (Tlaa, Tlad, Tlae), intermediate (Tlac, Tlaf), and low (Tlab). (Relative amounts: 1000: 100: 1.) Some thymic leukemias arising in (Tlab, Tlac) mice with genetically determined reduced levels of thymic TL were found to express TL molecules which were structurally indistinguishable from TL isolated from thymocytes but were present in larger amounts. This suggests that TL structural genes are intrinsically capable of full expression in all mice but that the Tla region of mice expressing an intermediate or low quantity of TL is marked by some feature which causes the thymocyte to express less than the full amount of TL possible.

Age Factors↗

Improved survival following combined radiation therapy and chemotherapy for unfavorable prognosis stage I-II non-Hodgkin's lymphomas.

A retrospective analysis of 144 patients with stage I-II non-Hodgkin's lymphoma (NHL) treated between June 1968 and December 1980 was performed. Patients were staged by bone marrow biopsy, chest radiography, blood chemistries, and either bipedal lymphangiography, computerized axial tomography, or surgical exploration of the abdomen. Patients were subclassified by extent of disease; minimal disease was defined as less than 10 cm and involved one or two contiguous sites, while patients with disease exceeding these limitations were considered to have extended stage I-II disease. Treatment consisted of radiation therapy (RT) alone in 74 patients and 70 patients were treated with chemotherapy with or without RT. Combination chemotherapy in patients with diffuse undifferentiated (DU) or diffuse histiocytic (DH) lymphoma resulted in a significantly higher 6-year survival as compared to patients treated with RT alone. For minimal disease DU/DH patients, the 6-year survival with chemotherapy +/- RT was 96% as compared to 61% with RT alone (P = .03). For extended disease DU/DH patients the 6-year survival with chemotherapy +/- RT was 56% as compared with 18% with RT alone (P = .003). This survival advantage from the initial use of chemotherapy was not seen in any of the other histologic subgroups.

Adolescent↗

Primary lymphomas of the central nervous system: patterns of failure and factors that influence survival.

Primary lymphomas of the CNS are rare tumors accounting for less than 2% of all extranodal non-Hodgkin's lymphomas. The treatment for this disease has been disappointing. Radiation therapy and surgery have produced consistently poor control of this disease, with a median survival of 15 months. We have reviewed ten cases of primary lymphoma of the CNS treated at the Joint Center for Radiation Therapy or Dana-Farber Cancer Institute (Boston) from 1968 to 1981. All patients had biopsy-proven CNS lymphomas without systemic disease at presentation. In our series, control of CNS lymphoma was seen only in patients receiving craniospinal radiation or CNS-penetrating chemotherapy.

Adolescent↗

The significance of the residual mediastinal mass in treated Hodgkin's disease.

The chest roentgenograms of 65 patients treated for Hodgkin's disease with mediastinal adenopathy were analyzed retrospectively to determine the incidence and significance of residual mediastinal abnormality after treatment. All patients were treated with radiation therapy, and 36 patients received additional chemotherapy. On completion of treatment, 57 (88%) of the 65 patients had some residual mediastinal abnormality. These were either minimal changes in the mediastinal shadow in 30 patients or a widening greater than 6 cm in 27 patients. In the latter group, 11 (40%) of 27 patients continued to have residual mediastinal widening one year after completion of therapy. These patients did not have a higher incidence of recurrence. Long-term follow-up (median, 48 months) revealed continued abnormalities in 24 (40%) of the original 57 patients. Mediastinal abnormalities are common at the end of radiation or combined modality therapy for Hodgkin's disease and do not by themselves indicate persistent active disease or an increased risk for relapse. We strongly recommend that additional chemotherapy or higher radiation doses beyond the initially planned course not be used for residual mediastinal widening.

Adolescent↗

Stage III Hodgkin's disease: improved survival with combined modality therapy as compared with radiation therapy alone.

This is a retrospective analysis of 120 patients with pathologically stage IIIA and IIIB Hodgkin's disease treated from April 1969 to December 1982. The median follow-up was 108 months. Treatment consisted of radiation therapy (RT) alone in 54 patients and combined radiation therapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy (CMT) in 66 patients. Stage III patients treated with CMT have an improved actuarial 12-year survival as compared with patients treated with RT alone with MOPP reserved for relapse (80% v 64%; P = .026). The 12-year actuarial freedom from first relapse by treatment for stage III patients is 83% and 40%, respectively (P less than .0001). Improved survivals following combined modality therapy are seen for the following subgroups of stage III patients: stage III2, 66% (CMT) v 44% (total nodal irradiation; TNI), P = .04; stage III1, 97% (CMT) v 73% (TNI), P = .05; stage III mixed cellularity or lymphocyte depletion histology, 94% (CMT) v 65% (TNI), P = .007; and stage III extensive splenic involvement, 77% (CMT) v 58% (TNI), P = .02. These survival differences are not seen in patients with nodular sclerosis or lymphocyte predominance histology or in patients with minimal splenic involvement. These data indicate that the initial use of CMT in stage III Hodgkin's disease results in an improved survival as compared with initial treatment with RT with MOPP reserved for relapse. Patients with limited Stage IIIA disease may still be candidates for radiation therapy alone.

Actuarial Analysis↗

Reduction of lethal graft-versus-host disease: transplantation of cultured murine bone marrow across minor histocompatibility differences.

The murine bone marrow culture technique was used to prepare donor marrow for bone marrow transplantation across minor histocompatibility complex differences. Previous studies have shown that theta-positive cells are rapidly lost from such cultures and that transplantation of cultured marrow across major histocompatibility complex differences results in a delay in the development of lethal graft-v-host disease (GVHD). In this study, a total of 1 to 2 X 10(7) nonadherent cells (740 to 1560 CFUs [colony-forming units]) from three-day-old cultures were used as a source of donor marrow. Three strain combinations were evaluated; LP/J into C57BL/6; BIO.BR into CBA/J; and C57BL/6 into LP/J. Donor mice were immunized with recipient spleen cells prior to culture in order to increase the graft-v-host response. For LP/J marrow into C57BL/6 mice, 5 X 10(7) donor spleen cells transplanted along with the marrow were needed to induce lethal GVHD. However, lethal GVHD was seen without the addition of spleen cells for BIO.BR into CBA/J and C57BL/6 into LP/J strain combinations. Most animals receiving fresh marrow were dead of GVHD five weeks after transplantation. With the use of cultured marrow the three-month survival was 80%, 51%, and 93%, respectively, for LP/J into C57BL/6, BIO.BR into CBA/J, and C57BL/6 into LP/J strain combinations. Long-term donor engraftment in all recipient animals receiving cultured marrow was confirmed by analyzing hemoglobin polymorphisms between the strain combinations. These results demonstrate that in contrast to transplantation across major histocompatibility complex differences, the use of cultured cells for bone marrow transplantation across minor histocompatibility complex differences allows for engraftment while reducing the risk of lethal GVHD.

Animals↗

Lethal graft-versus-host disease: modification with allogeneic cultured donor cells.

The use of the bone marrow culture technique was studied as a means to prepare donor marrow for bone marrow transplantation to avoid lethal graft-versus-host disease (GVHD). Preliminary experiments demonstrated the rapid loss of theta-positive cells in such cultures, so that theta-positive cells were not detected after 6 days. Initial experiments in C3H/HeJ (H-2k, Hbbd) recipients prepared with 900 rad demonstrated improved survival when 3-day cultured C57BL/6 (H-2b, Hbbs) donor cells were used in place of hind limb marrow for transplantation. However, hemoglobin typing of recipient animals revealed only short-term donor engraftment, with competitive repopulation of recipient marrow occurring. Subsequent experiments were done in 1,200-rad prepared recipients, with long-term donor engraftment demonstrated. The majority of 1,200-rad prepared animals receiving cultured allogeneic cells died of GVHD, but animals receiving 28-day cultured cells had an improved 90-day survival and a delay in GVHD development over animals receiving hind limb marrow or marrow from shorter times in culture. In addition, animals receiving anti-theta-treated, 3-day nonadherent cells had an improved survival (44%) over animals receiving anti-theta-treated hind limb marrow (20%). These experiments demonstrate modest benefit for the use of cultured cells in bone marrow transplantation across major H-2 histocompatibility complex differences.

Animals↗

Functional organization of the hematopoietic stem cell compartment: implications for cancer and its therapy.

Recent discoveries indicate that hematopoietic stem cells have limits on their proliferative capacity and are unable to divide indefinitely. There is great heterogeneity within the compartment as to the extent of this proliferative limitation. At any given time it appears that hematopoiesis is maintained by the progeny of only a few stem cells. When these are exhausted the progeny from other stem cells take their place. The observations of proliferative limitation, heterogeneity, and clonal succession must be incorporated into any model of stem cell organization. These new discoveries and the models incorporating them have important clinical implications. They may explain the inability of normal tissues to develop drug resistance and they also offer a mechanism by which cell renewal systems decrease the development of malignancies. In the selection of chemotherapeutic agents not only the effectiveness of the drug upon the tumor must be considered, but also how specific agents affect the stem cell compartment. These data have important implications in the use of bone marrow transplantation for both malignant and nonmalignant disease.

Age Factors↗

Peri- and paracardial involvement in lymphoma: a radiographic study of 11 cases.

Eleven patients with pericardiac and paracardiac lymphomatous involvement were studied. Computed tomography (CT) of the chest was compared to plain chest films for its ability to define the sites and extent of involvement in the paracardiac area. Nine of the 11 patients had abnormalities on chest radiography, which included abnormal contours in the fat pad areas and along the heart border, or an enlarged cardiac silhouette. Two patients had normal cardiac silhouettes; however, CT showed definite abnormalities. CT differentiated adenopathy from fat pads in two patients and pericardial effusion from cardiomegaly or paracardiac adenopathy in two patients. The exact location and extent of the paracardiac adenopathy initially seen on chest film was defined by CT. Careful analysis of the peri- and paracardiac areas by plain films and CT is essential to the diagnosis and the proper management of patients with Hodgkin and non-Hodgkin lymphoma.

Adolescent↗

Circulating lymphocyte populations in Hodgkin's disease after mantle and paraaortic irradiation.

The effect of mantle and paraaortic radiation on peripheral blood lymphocytes was studied in 11 previously untreated patients with early stage Hodgkin's disease using a series of monoclonal antibodies defining immunoregulatory lymphoid cells. Immediately following the completion of radiotherapy, there was a significant reduction in the number of lymphocytes and the percent of circulating T cells. This acute decrease in T cells was due to a marked diminution in the number of inducer T cells, while the fraction of suppressor T cells remained constant. These changes persisted for up to 12 mo and were accompanied by a later increase in the fraction of circulating B lymphocytes and cells bearing surface Ia. It thus appears that mantle and paraaortic radiotherapy causes a relatively selective reduction in the inducer T-cell population. The implications of a change in the ratio of inducer to suppressor T cells is discussed.

Antibodies, Monoclonal↗

The role of postoperative local or regional irradiation in the treatment of stage I ovarian cancer.

Histological grade and cell type were major prognostic factors in a retrospective study of 63 patients with Stage I epithelial carcinoma of the ovary. Grading by architectural pattern seemed to predict relapse better than cytological grading. With serous, mucinous, and endometrioid cystadenocarcinomas, relapses increased with higher grades. Relapse occurred in none of 18 tumors of borderline malignancy, 2 of 27 (7%) with Grade I or II tumor, and 4 of 6 (67%) with Grade III. The upper abdomen and pelvis were both at risk. Because most recurrences were limited to the peritoneal surface in Grade III serous, mucinous, and endometrioid carcinoma, local and regional radiation therapy are justified; postoperative therapy is not recommended for borderline or Grade I tumors unless ascites or cytological evidence of peritoneal disease is present. Clear-cell carcinoma was uncommon and unfavorable; of 12 cases, 5 involved relapse, with 3 recurrences developing outside the abdomen.

Adult↗

Cell types associated with fibronectin in long-term mouse bone marrow cultures.

The formation of fibronectin matrix was studied in long-term mouse bone marrow cultures. Stromal and hematopoietic cells were observed in situ under phase contrast optics and quantified according to their staining characteristics on smear preparations. Surface fibronectin was demonstrated by indirect immunofluorescence. While only stromal and no hematopoietic cells participated, various stromal cell types differed in their expression of cell surface fibronectin: Reticulum cells contributed the major portion of fibronectin matrix. Elongated, meshwork-forming histiocytes expressed some surface fibronectin, while the flattened, macrophagic histiocytes remained fibronectin negative. These findings were recapitulated during regeneration of scrape wounds in the adherent layers. Isolated fibronectin matrix did not support hematopoietic cell adherence or maintenance, although it had marked effects on stromal cells.

Adipose Tissue↗

Long-term complications of MOPP chemotherapy in patients with Hodgkin's disease.

Two hundred and sixty-three patients in long-term remission from Hodgkin's disease were evaluated for complications of chemotherapy. All patients were interviewed by telephone conversation and reported complications were documented by chart review. Treatment consisted of mantle and para-aortic irradiation in 127 patients, total nodal irradiation (TNI) in 32, TNI and MOPP in 34, and mechlorethamine, vincristine, prednisone, and procarbazine (MOPP) chemotherapy alone or with lesser irradiation in 70. In this study, greater than 90% of the men who received MOPP remain infertile. In contrast, a substantial portion of female patients treated with MOPP chemotherapy have retained normal menses (58%) and only a small proportion have had persistent amenorrhea (9%). Five of eight female patients desiring families after MOPP chemotherapy have had normal children. The risk of developing a major infection requiring hospitalization was greatest in those patients who had received TNI and MOPP chemotherapy. The risk of developing a herpes zoster infection was greatest during or within the first year following therapy and was greatest in those patients receiving combined radiation therapy and chemotherapy. Nearly 100% of patients continue to lead normal lives following treatment for Hodgkin's disease. Only a small percent of patients (1.5%) have been totally disabled following treatment.

Adolescent↗

Anatomic substages of stage IIIA Hodgkin's disease: followup of a collaborative study.

The clinical significance of anatomic substage was reassessed in a previously reported series of 130 patients with Hodgkin's disease in pathologic stage IIIA. For 100 patients, followup was greater than 8 years. By definition, stage III1 disease includes involvement of spleen or splenic, celiac, or portal nodes, or any combination of these; stage III2 disease includes involvement of para-aortic, iliac, or mesenteric nodes, with or without upper abdominal involvement. Both 8-year relapse-free survival (71% versus 40%) and 8-year overall survival (80% versus 54%) were better in stage III1A than in III2A patients (P less than 0.001). For stage III1A, relapse-free survival was better in patients receiving radiotherapy alone as initial treatment (92% versus 60%, P less than 0.002). However, 8 year overall survival rates in these two treatment groups were not significantly different (88% versus 76%, P = 0.20). For stage III2A, both relapse-free survival at 8 years (84% versus 19%, P less than 0.001) and overall survival at 8 years (84% versus 41%, P less than 0.01) were superior in patients receiving combined modality therapy. Anatomic substage is a critical prognostic variable, especially if standard total nodal radiotherapy is considered as one of the therapeutic options.

Adult↗

Influence of mediastinal adenopathy on site and frequency of relapse in patients with Hodgkin's disease.

Between April 1969 and July 1979, 267 patients with surgically staged IA-IIB Hodgkin's disease and 31 with clinically staged IIE or IV Hodgkin's disease were treated; disease was limited to the area above the diaphragm. Three separate groups of patients with mediastinal adenopathy were identified. Patients with disease limited to the mediastinum had a favorable prognosis, and treatment with mantle followed by para-aortic irradiation has resulted in 85% relapse-free survival and 100% overall survival at 8 years. Surgically staged patients with large diameter mediastinal adenopathy (greater than 0.33 of the thoracic diameter) have a high relapse rate with radiation therapy alone. The use of combined modality therapy has reduced the risk of relapse in these patients, but the survival remains higher whether MOPP is used initially or at relapse. Clinically staged IIE patients or stage IV patients with extensive extranodal disease limited to the thoracic cavity were treated with chemotherapy and involved- or extended-field irradiation. These patients had a 5-year survival of 66% with large mediastinal adenopathy and 90% with lesser mediastinal disease.

Hodgkin Disease↗