Biomedical subjects

P Mauch

Publications and source records attributed to P Mauch.

At least 55 records · Page 3Linked to original sources

PubMed1995

Removal of carcinoma cells from contaminated bone marrow using the lipophilic cation rhodamine 123.

Autologous bone marrow transplants for solid tumor treatment are severely limited by the potential presence of residual cancer cells in the reinfused bone marrow and can lead to future tumor recurrence. This article presents a novel method of removing carcinoma cells from bone marrow with contaminating cancer cells. This method is based on our previous studies demonstrating that carcinoma cells have a higher uptake of lipophilic cations such as rhodamine 123 than their normal epithelial counterparts. When the relative differences in rhodamine 123 uptake are quantified, carcinoma cell lines demonstrated a 7.4-21 times greater uptake of rhodamine 123 than normal mouse bone marrow cells. More important, when normal bone marrow cells and carcinoma cell lines are mixed to simulate carcinoma-contaminated bone marrow, individual cell populations continue to exhibit characteristic and identifiable relative differences (10-20 times) in rhodamine 123 uptake. Differential sorting of bone marrow/carcinoma cell mixtures with respect to rhodamine 123 fluorescence intensity resulted in the removal of 95-99% of the "contaminating carcinoma cells." The recovered bone marrow cells were fully viable as ascertained by their ability to form splenic colonies. In our preliminary experiments, sorted bone marrow cells transplanted into lethally irradiated C57BL6 mice allowed the mice to survive for more than 8 months. In light of these promising results, we propose that lipophilic cations may play a role in the purification of autologous bone marrow used in transplants for patients with advanced solid tumors.

Animals↗

PubMed1994

Histopathologic grading of nodular sclerosis Hodgkin's disease. Lack of prognostic significance in 254 surgically staged patients.

BACKGROUND: The cellular composition of nodular sclerosis Hodgkin's disease (NS-HD) varies greatly from patient to patient. It is unclear whether subclassifying NS-HD based on cellular composition has prognostic value, because reported studies examining this issue have shown conflicting results. METHODS: The initial pathology slides of 254 surgically staged patients with NS-HD treated at the Joint Center for Radiation Therapy were reviewed and subclassified according to British National Lymphoma Investigation criteria. The median follow-up time was 123 months. RESULTS: A total of 211 patients were classified NS I histology (83%), and 43 patients were classified NS II (17%). There were no differences in the distribution of NS I/NS II patients by age, number of sites of disease, B symptoms, or extent of mediastinal disease. Patients with NS II disease were more likely to be male (P = 0.001), and to have pathologic Stage I-II disease (P = 0.07). The 15-year actuarial rates of disease-free survival were 77 and 80% for NS I and NS II patients, respectively (P = not significant). The 15-year overall survival rates were 87 and 93% for NS I and NS II, respectively (P = not significant). No differences were seen between NS I and NS II patients for overall or disease free survival when analyzed separately by pathologic stage or by initial treatment. Similarly, no differences between NS I and NS II patients were seen in the large subgroup of 155 pathologic stage IA-IIA patients treated with radiation therapy alone. When other histologic parameters were analyzed separately, no differences were seen in the frequency of relapse between the groups based on extent of necrosis, atypia, fibrosis, variant atypia, variant syncytia, eosinophilia, or number of mitoses. CONCLUSIONS: The histologic subclassification of Hodgkin's disease had no prognostic significance in this group of surgically staged, uniformly treated patients.

Adolescent↗

PubMed1994

Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin's lymphoma.

PURPOSE: To determine the incidence, natural history, and risk factors associated with myelodysplastic syndrome (MDS) occurring as a late complication following autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma. METHODS: We retrospectively reviewed the charts of all 262 patients who underwent autologous bone marrow transplantation for non-Hodgkin's lymphoma at the Dana-Farber Cancer Institute from 1982 through 1991. Although patients received a variety of treatments before they were eligible for transplant, identical myeloablative therapy (cyclophosphamide 60 mg/kg/d for 2 days plus total-body irradiation twice daily for 3 days) was administered in each case. By collecting data on pretransplant and early posttransplant variables, we attempted to identify risk factors for the development of MDS. RESULTS: The crude overall incidence of posttransplant MDS or acute myeloid leukemia (AML) was 7.6%. The actuarial risk at 6 years was 18% +/- 9%. The median time of onset was 31 months (range, 10 to 101) after transplant or 69 months (range, 27 to 141) after initial treatment for lymphoma. Pretreatment variables predictive for the development of MDS (univariate analysis) included prolonged interval between initial treatment and the transplant procedure (P = .003), increased duration of exposure to chemotherapy (P = .019) or to alkylating agents (P = .045), and use of radiation therapy (P = .032) or pelvic radiation (P = .003) before transplant. CONCLUSION: MDS is a potential complication of autologous bone marrow transplantation for non-Hodgkin's lymphoma; bone marrow stem-cell damage sustained before the transplant may be the most important risk factor.

Adult↗

PubMed1994

Synergistic effects of interleukin-11 with other growth factors on the expansion of murine hematopoietic progenitors and maintenance of stem cells in liquid culture.

The effect of interleukin-11 (IL-11), alone and in combination with other hematopoietic growth factors, was studied in liquid suspension cultures of murine bone marrow. Stem and progenitor cell contents of input bone marrow 2 days after 5-fluorouracil (5-FU) treatment (FU2dBM) and lineage-depleted, Sca-1-positive FU2dBM (Lin-Sca+Fu2dBM) were compared with output values obtained after 6 days in different growth factor combinations. Stem and progenitor cell recoveries were measured by long-term in vivo competitive repopulation, spleen colony-forming unit (CFU-S), and in vitro limiting dilution long-term bone marrow culture (cobblestone area-forming cell [CAFC]) assays. IL-11, IL-3, IL-6, and Steel factor (SF) were tested separately and in combinations of two, three, and four factors. IL-11 was incapable of maintaining the survival of stem or progenitor cells as a single agent but synergized with either IL-3 or SF to expand progenitor cell output in cultures of FU2dBM. IL-11 greatly enhanced progenitor cell expansion from FU2dBM when added to two- and three-factor combinations of SF, IL-3, and IL-6. The recovery of long-term repopulating ability was enhanced four-fold by incubation in SF plus IL-11 compared to SF alone. IL-11 in combination with SF, IL-3, and IL-6 stimulated a 24,000-fold expansion of progenitor cells from stem cell-enriched Lin-Sca+FU2dBM. Overall, the results indicate that IL-11 is a potent synergistic factor for stem cell proliferation and expansion of progenitors in liquid culture.

Animals↗

PubMed1993

[Treatment of early stage Hodgkin disease].

In early stage Hodgkin's disease the optimal choice of treatment is still an unresolved issue. Twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out world-wide. The preliminary results of a global meta-analysis of these trials indicate that we still do not definitively know whether or not the early addition of prophylactic chemotherapy improves survival. Arguments in favour of early chemotherapy are: that laparotomy may be avoided, that radiation fields and doses may perhaps be reduced, and that the stress of experiencing a relapse is avoided in many patients. The major argument against early chemotherapy is: that by careful staging and selection of patients and by careful radiotherapy techniques the number of patients exposed to potentially toxic chemotherapy may be kept at a minimum. Recently, trials have been carried out testing chemotherapy alone, results are, however, conflicting. In order not to jeopardize the good results achieved with the standard treatments developed over the last three decades, newer treatment approaches should be carefully tested in large randomized trials before being implemented for general clinical use.

Female↗

PubMed1993

Wide-field radiation therapy with or without chemotherapy for patients with Hodgkin disease in relapse after initial combination chemotherapy.

BACKGROUND: Patients with Hodgkin disease who have relapses after initial chemotherapy (CT) appear to have a poor prognosis, especially if the duration of the first complete remission (CR) was short. The authors performed a retrospective analysis of patients with Hodgkin disease whose relapse after combination CT was limited to nodal sites; their aim was to study the prognosis of this selected subgroup of patients. METHODS: In 28 patients with Hodgkin disease who had relapses in nodal sites after combination CT alone, the disease was restaged carefully to rule out simultaneous extranodal recurrences. Then the patients were treated with wide-field, high-dose radiation therapy (RT) with or without additional CT with curative intent between 1971 and 1987 at the Joint Center for Radiation Therapy. Fourteen patients were in first relapse and were treated with combination CT followed by RT. The remaining 14 patients (8 who were in first relapse and 6 who were in second relapse) were treated with RT alone. RT techniques were similar to those recommended for early-stage disease. RESULTS: The 7-year actuarial freedom from relapse and survival rates for the patients retreated with CT and RT were 93% and 85%, respectively, as compared with 36% and 36% for patients retreated with RT alone. There was a significant difference for freedom from relapse (P = 0.002) and survival (P = 0.03), favoring patients retreated with both CT and RT. CONCLUSIONS: This retrospective study demonstrates that RT combined with second-line CT can result in a high percentage of durable remissions in patients who have relapses primarily in nodal sites after original treatment with combination CT alone. These durable remissions are seen even in patients who have only a brief CR after initial CT.

Adolescent↗

PubMed1993

Pediatric stage IV Hodgkin disease. Long-term survival.

BACKGROUND: The optimal treatment for Stage IV Hodgkin disease (HD) remains uncertain, particularly the role of radiation therapy (RT). METHODS: A retrospective review of 43 children, 18 years of age or younger, who were seen and treated for Stage IV HD between June 1970 and June 1988, was performed. All patients were treated with combination chemotherapy (CT), and 20 patients received RT after CT (combined-modality therapy, CMT). CT consisted of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) in 41 patients and both MOPP and doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine in two patients. RT was added for patients who had a partial response (PR) to CT (n = 11) and/or for initial bulky thoracic disease (n = 12). RESULTS: With a median follow-up of 83 months, the 7-year actuarial freedom from progression (FFP) and survival rates for all patients were 69% and 78%, respectively. For patients achieving a complete response (CR) to CT, the 7-year FFP rate was 73% and for patients with a PR it was 90% (P value not significant). The actuarial overall survival rates at 7 years were 88% for patients with CR versus 80% for patients with PR. In contrast, patients with either no response (one patient) or progressive disease (four patients) after CT had a significantly worse prognosis than patients with CR, with a 7-year actuarial survival rate of 40% (P = 0.006). FFP after CT alone was significantly more prevalent in patients with Stage IVA (11 of 13 patients) than in patients with Stage IVB disease (2 of 10 patients; P = 0.003). For these symptomatic patients, failures were almost exclusively (seven of eight patients) in sites of initial nodal disease. The addition of adjuvant RT improved the progression-free survival for patients with B symptoms: 2 of 13 patients had relapses after CMT versus 8 of 10 patients treated with CT alone (P = 0.003). CONCLUSIONS: This retrospective analysis of MOPP alone compared with MOPP plus RT showed a significant difference in FFP in patients with Stage IVB HD favoring CMT.

Adolescent↗

PubMed1993

Sex differences in risk of second malignant tumours after Hodgkin's disease in childhood.

There have been reports of a high incidence of second malignant disorders in survivors of Hodgkin's disease. We studied the cumulative incidence of second tumours in 191 children, who were 16 years or younger at diagnosis, with stage IA-IVB Hodgkin's disease, treated at the Joint Center for Radiation Therapy, Boston, between 1969 and 1988. The 10-year actuarial survival was 89 (SE 2)%. The median follow-up time was 11 (range 3-21) years from diagnosis. 109 children were initially treated with radiotherapy alone, 61 received chemotherapy and radiotherapy, and 21 received chemotherapy alone. Second tumours arose in 15 patients 6-20 years after the diagnosis of Hodgkin's disease. The estimated cumulative incidence of second malignant disorders at 15 years was 12 (4)% overall. 10 of the second tumours arose among 66 female patients, compared with 5 among 125 male patients (cumulative incidence 24 [9] vs 5 [3]%). The relative risk of a second tumour for female compared with male patients was 4.5 (95% CI 1.4-15.1; p = 0.013). For male patients, the observed incidence of second tumours was 18 times that expected for the normal population (95% CI 6-42), whereas for female patients it was 57 times that expected (27-105). 13 of the second malignant disorders were solid tumours, including 4 breast cancers. Thus, the risk of a child treated for Hodgkin's disease developing a second tumour is higher for girls than for boys. The cumulative incidence of second cancers increases from 10 years after treatment. These findings emphasise the importance of continued surveillance in patients treated for Hodgkin's disease.

Adolescent↗

PubMed1993

Mobilization of hematopoietic stem and progenitor cell subpopulations from the marrow to the blood of mice following cyclophosphamide and/or granulocyte colony-stimulating factor.

Committed progenitor cells and primitive stem cells mediate early and sustained engraftment, respectively, after lethal irradiation and stem cell transplantation. Peripheral blood stem cells (PBSC) from unstimulated mice are deficient in both cell types. To study techniques to mobilize both progenitor cells and primitive stem cells from the marrow to the blood, we collected peripheral blood from C57BL/6 mice 6 to 7 days after a single dose of cyclophosphamide (CY; 200 mg/kg intraperitoneally), after recombinant human granulocyte colony-stimulating factor (rhG-CSF) (250 micrograms/kg/d twice per day subcutaneously for 4 days), or after CY followed by G-CSF. Significant increases in white blood cell counts (1.6- to 2.7-fold) and circulating day 8 colony-forming unit spleen (CFU-S) (11- to 36-fold) were seen with all three mobilization methods compared with unstimulated control mice. Transplantation of mobilized blood stem cells into lethally irradiated hosts decreased the time to erythroid engraftment. Blood stem cells were analyzed for primitive stem cell content by Rs, an assay for CFU-S self-renewal, and competitive repopulation index (CRI), an assay of long-term repopulating ability. The primitive stem cell content of unstimulated blood was clearly deficient, but was significantly increased following mobilization, approaching normal bone marrow levels. These results were confirmed by an in vitro limiting dilution long-term culture assay that measures the frequency of progenitor cells and primitive stem cells. Mobilization following CY + G-CSF was accompanied by a marked loss of both progenitor cells and primitive stem cells in the marrow. In contrast, following G-CSF alone the progenitor cell and primitive stem cell content of the marrow was unchanged. Stem cell mobilization following CY + G-CSF was not affected by previous exposure of donors to cytosine arabinoside or cyclophosphamide, but was significantly reduced by previous exposure to busulfan. These data show that stem cell content in the blood may reach near-normal marrow levels after mobilization, the mobilization from the marrow to the blood is temporary and reversible, the specific technique used may mobilize different subpopulations of stem cells, and the type of prior chemotherapy may influence the ability to mobilize stem cells into the blood.

Animals↗

PubMed1993

Long-term follow-up of a phase III study of recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid malignancies.

One hundred and twenty-eight patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and acute lymphoblastic leukemia (ALL) previously reported from a phase III trial of rhGM-CSF or placebo following autologous bone marrow transplantation (ABMT) were investigated for the development of late toxicities. Median follow-up is 36 months. No apparent long-term deleterious effects on BM function were observed. Moreover, disease-free survival and overall survival were similar for patients on both treatment arms, arguing for the long-term safety of recombinant human granulocyte macrophage-colony-stimulating factor (rhGM-CSF). The only factors predictive for both a high risk of relapse over time and mortality were having the diagnosis of ALL and/or undergoing ABMT in resistant relapse. We attempted to identify clinical variables before BM harvest, at the time of marrow infusion, or events within the first 100 days posttransplant, which might predict speed of neutrophil recovery in the setting of placebo or rhGM-CSF administration after ABMT. Only previous exposure to agents that deplete stem cells led to a significant delay in neutrophil recovery, suggesting their avoidance in patients who may undergo ABMT. Nevertheless, even those patients benefited from rhGM-CSF. For all patients, rhGM-CSF and agents that deplete stem cells were the strongest independent predictors for neutrophil engraftment. With the increasing use of newer hematopoietic growth factors both alone and in combination, long-term follow-up is essential to confirm the same safety that we report with rhGM-CSF.

Adolescent↗

PubMed1993

Autologous bone marrow transplantation in poor-prognosis intermediate-grade and high-grade B-cell non-Hodgkin's lymphoma in first remission: a pilot study.

PURPOSE: Using high-dose therapy and autologous bone marrow transplantation (ABMT) to overcome cellular resistance and eradicate minimal disease, we initiated a pilot study during first remission in patients with non-Hodgkin's lymphoma (NHL) to examine whether the long-term disease-free survival (DFS) rate can be improved for patients with poor-prognosis intermediate/high-grade NHL. PATIENTS AND METHODS: Twenty-six patients with advanced-stage diffuse intermediate/high-grade B-cell NHL (including 16 patients with diffuse small cleaved-cell [DSC]) were selected at presentation by histologic and clinical characteristics to have less than a 25% probability of long-term DFS with conventional treatment. After induction chemotherapy, 16 patients were in complete remission (CR) and 10 were in a minimal disease state. Patients were then treated with high-dose cyclophosphamide, total-body irradiation (TBI), and anti-B-cell monoclonal antibody-purged ABMT. RESULTS: Following ABMT, no acute in-hospital treatment deaths occurred, and engraftment of granulocytes and platelets was significantly faster than for patients undergoing ABMT who were in second or subsequent remission. Of 26 patients, 21 remain in CR maintained without continued therapy, three relapsed in sites of prior nodal disease (4.8, 5.4, and 28 months post-ABMT), and two died in remission. The DFS rate is estimated to be 85% at 28 months and thereafter. The median follow-up period for the 21 patients who are alive and disease-free is 32 months. CONCLUSION: This pilot study suggests that consolidation of first remission with ABMT may improve the long-term DFS rate for diffuse intermediate/high-grade NHL patients at high risk for relapse.

Adult↗

PubMed1993

Primary Ki-1 anaplastic large-cell lymphoma in adults: clinical characteristics and therapeutic outcome.

PURPOSE: A study was undertaken to improve our understanding of the clinicopathologic features and therapeutic outcome for adults with primary Ki-1 anaplastic large-cell lymphoma (ALCL). PATIENTS AND METHODS: A retrospective review of records of 31 adult patients with primary Ki-1 ALCL was performed. The analysis included stage and distribution of disease, tumor-cell phenotype, response to initial and salvage therapy, and disease-free and overall survival. RESULTS: The median age of patients was 44 years (range, 16 to 86). Forty-eight percent of patients tested had lymphomas of T-cell phenotype, 30% lymphomas of B-cell phenotype, and 22% of non-T-, non-B-cell phenotype. Twenty-nine percent of patients had stages I and II disease, 65% demonstrated extranodal involvement, and 32% had skin involvement at presentation. Most patients received intensive chemotherapy and 48% achieved a sustained complete remission (CR), with an additional 17% of patients treated successfully with salvage therapy. Stage was highly predictive of achieving a sustained CR, but bulk disease and B symptoms did not predict for relapse after initial therapy or survival. Of seven patients who underwent autologous bone marrow transplantation (ABMT), three remain disease-free 9 to 42 months after transplant. CONCLUSION: Patients with Ki-1 ALCL have a high frequency of advanced-stage disease and extranodal involvement and are more likely to have tumors of T-cell phenotype than patients with large-cell lymphoma. However, response to standard lymphoma chemotherapy is similar to other patients with large-cell lymphoma, with a high remission rate in early-stage disease. Patients with advanced-stage disease have a poor remission duration and may require more intensive therapy, as may also be the case with large-cell lymphoma.

Adolescent↗

PubMed1993

Large-cell and immunoblastic lymphoma of the mediastinum: prognostic features and treatment outcome in 57 patients.

PURPOSE: A retrospective study was performed to define clinical characteristics and therapeutic outcome for patients with large-cell and immunoblastic lymphoma of the mediastinum. PATIENTS AND METHODS: Fifty-seven patients who presented with primary, mediastinal large-cell and immunoblastic lymphoma were retrospectively studied to determine initial sites of disease, radiologic characteristics, treatment, outcome, and factors that have prognostic significance for progression-free and overall survival. RESULTS: Fifty-six of the 57 patients had disease that was confined to sites above the diaphragm. Bulky disease and extensive intrathoracic infiltration were common in these patients. All patients were treated with intensive chemotherapy regimens, and 44% of patients received chest irradiation. The overall 5-year survival by Kaplan-Meier estimation was 50% with a freedom-from-relapse rate of 45%. Predictors of disease relapse after chemotherapy included the presence of a pleural effusion (P = .015), a number of involved extranodal sites (P < .01), and a lactic dehydrogenase (LDH) ratio > 3.0 (LDH value/upper limit of assay; P = .04) as well as an incomplete treatment response as evidenced by residual mass on chest radiograph (P = .02) or persistent gallium 67 avidity (P = .01) after chemotherapy. Predictors of decreased survival included the presence of pleural effusion (P = .001), the number of involved extranodal sites (P = .022), and a positive posttreatment 67Ga scan (P = .027). CONCLUSION: Patients with primary mediastinal large-cell and immunoblastic lymphoma have an approximate 50% chance of surviving disease-free after initial therapy. The presence of pleural effusion at presentation was associated with an extremely poor outcome. Bulk disease per se was a negative predictive factor only in patients without pleural effusions when compared with patients who did not have bulk disease. In addition, all patients with involvement of two or more extranodal sites relapsed when treated with standard chemotherapy.

Actuarial Analysis↗

PubMed1993

Hematopoietic stem cell deficit of transplanted bone marrow previously exposed to cytotoxic agents.

High-dose chemotherapy and/or total body irradiation followed by autologous bone marrow rescue has improved the survival of patients with a variety of malignancies. Candidates for autologous bone marrow transplantation (ABMT) often have received prior exposure to cytotoxic agents, some of which may damage primitive stem cells. We have developed an in vivo murine model to evaluate the effects of a number of individual cytotoxic agents on the ability of syngeneic donor marrow to provide long-term hematopoiesis in recipients following high-dose total body irradiation. Marrow was experimentally obtained by giving donor mice 6 weekly injections of saline, cytosine arabinoside, cyclophosphamide, cisplatin, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), or busulfan, drugs known to have differing effects on primitive hematopoietic stem cells. After time to allow recovery of marrow and peripheral blood counts, 1 x 10(7) marrow cells from these mice were transplanted into lethally irradiated syngeneic recipients. Five to 6 months after marrow transplantation, the quality of long-term hematopoietic recovery was measured by WBC counts, marrow cellularity, CFU-S content, and determinations of stem cell self-renewal. Abnormalities were noted with the use of donor marrow exposed to all cytotoxic agents. Recipients of marrow previously exposed to cytosine arabinoside, an agent that spares the most primitive stem cells, were the least affected. Recipients of marrow previously exposed to busulfan, an agent known to damage primitive stem cells, were most affected with a decrease in peripheral blood counts, marrow cellularity, stem cell content, self-renewal capacity, and long-term survival. A decrease in hematopoietic stem cell self-renewal was seen in recipients of marrow previously exposed to cyclophosphamide, cisplatin, and BCNU even when marrow cellularity and CFU-S content were normal. These data suggest that the capacity of syngeneic donor marrow to provide long-term hematopoiesis in lethally irradiated recipients is dependent on its donor marrow primitive stem cell content. Long-term hematopoiesis may be severely compromised in recipients of donor stem cells previously exposed to cytotoxic agents which damage primitive stem cells.

Animals↗

PubMed1993

Quantitation of murine hematopoietic stem cells in vitro by limiting dilution analysis of cobblestone area formation on a clonal stromal cell line.

Murine hematopoietic stem cells with varying proliferative capacity can be assayed by limiting dilution analysis of "cobblestone area" (CA) formation on stromal layers in microlong-term bone marrow cultures. Cobblestone area forming cell (CAFC) frequency determined at early time points (day 7) correlates with mature stem cells measured as day 8 CFU-S, whereas CAFC frequency determined at day 28 correlates more closely with long-term marrow repopulating ability. Here we report a modification of the CAFC assay in which a clonal bone marrow stromal cell line, GB1/6, is substituted for fresh marrow-derived stromal layers. This modification simplifies the initial culture setup, eliminates inhomogeneities in the stromal layer and reduces the need for mice. Normal bone marrow CAFC frequencies were the same for both types of stromal cell underlayer, demonstrating the ability of a clonal cell line to completely replace the heterogeneous microenvironment of fresh stroma for in vitro stem cell support.

Animals↗

PubMed1993

Mutagenesis after therapy for Hodgkin's disease.

Therapy for Hodgkin's disease has been associated with a significant increase in risk for second cancers. To begin an investigation of the association of therapy-induced genetic damage with this risk, somatic mutations at the hypoxanthine phosphoribosyltransferase locus were measured in lymphocytes from patients previously treated for Hodgkin's disease. The results demonstrate that a subset of patients have persistently elevated mutation frequencies, perhaps suggesting that these individuals are among those at significant risk of second cancer development.

Adolescent↗

PubMed1992

Coronary artery disease mortality in patients treated for Hodgkin's disease.

The authors conducted a follow-up study of the association between mediastinal irradiation, chemotherapy, and mortality from coronary artery disease in 4665 patients treated for Hodgkin's disease. Study subjects were followed after the diagnosis of Hodgkin's disease until death or the closing date of the study. The average duration of follow-up was 7 years; 2415 patients died, and 124 cases of coronary artery disease were identified from death certificates, including 68 cases of acute myocardial infarction. The age-adjusted relative risks (RR) of death with any coronary artery disease after mediastinal irradiation and after chemotherapy were 1.87 (95% confidence interval [CI], 0.92 to 3.80) and 1.28 (CI, 0.77 to 2.15), respectively. A significantly increased risk of death in the subcategory myocardial infarction was observed after mediastinal irradiation (RR, 2.56; CI, 1.11 to 5.93) but not after chemotherapy (RR, 0.97; CI, 0.53 to 1.77). These results support the hypothesis that radiation therapy to the mediastinum increases the risk of coronary artery disease.

Adolescent↗

PubMed1992

Three-dimensional dose distribution of total body irradiation by a dual source total body irradiator.

This study describes the three-dimensional dosimetric characteristics of total body irradiation by our dedicated irradiation unit, which consists of two modified 4-MV linear accelerators mounted opposite each other, providing a field size of 220 cm x 80 cm at the midplane. Our dose calculation algorithm considers the three-dimensional contour of the patient to evaluate the primary and scatter doses. The data base for the calculation includes tissue-to-maximum ratios measured for the large fields. The lung dose correction was calculated using the methods of Batho or ratio of TMR. The accuracy of the calculated dose distributions was verified by measurements with ionization chambers in a humanoid phantom. We also describe and verified a technique to achieve desirable midline lung doses using lead shields. The flexibility and the accuracy of the planning system offers the potential in optimizing the therapeutic ratio for total body treatments.

Algorithms↗