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M Flentje

Publications and source records attributed to M Flentje.

At least 91 records · Page 5Linked to original sources
PubMed1996

High-dose therapy with peripheral blood progenitor cell transplantation in low-grade non-Hodgkin's lymphoma.

It was the objective of our study to evaluate the efficacy of a sequential high-dose therapy with peripheral blood progenitor cell (PBPC) support in patients with low-grade non-Hodgkin's lymphoma (NHL). Since July 1991, 48 patients (23 male/25 female) with a median age of 43 years (range 26-55) were included in the study. At the time of entry, 28 patients were in first and seven in second or higher remission. Twelve patients had relapse of disease and one patient had tumor progression. PBPC were collected during granulocyte colony-stimulating factor (G-CSF)-enhanced leukocyte recovery following treatment with high-dose cytarabine and mitoxantrone (HAM). A median of two leukaphereses (range 2-7) resulted in 6.9 x 10(6) CD34+ cells/kg (median, range 2.1 x 10(6)-38.8 x 10(6)). A comparison was made between the harvests obtained from patients in first remission and those from patients in second remission, in relapse or progressive disease. Patients mobilized in first remission tended to have a greater collection efficiency for CD34+ cells comprising a significantly greater proportion of more primitive CD34+/Thy-1+ progenitor cells. Conversely, leukapheresis (LP) products collected during first remission contained a significantly smaller proportion of CD34+/CD45RA+ cells and CD34+/c-kit+ cells, subsets which reflect a more differentiated progenitor cell stage. Following high-dose therapy and PBPC autografting, the median time to reach platelets > or = 20 x 10(9)/l and neutrophils > or = 0.5 x 10(9)/l and 12 and 13 days, respectively. Two patients died of treatment-related toxic organ failure. Thirty-nine patients are alive in remission after a median follow-up time of 15 months (range 1-31), while seven patients relapsed between 5 and 29 months post-transplantation. Except for one patient autografted in first remission, the patients with relapse had a history of previous relapse or progressive disease. Since the probability of disease-free survival appears to be related to the disease status at the time of autografting, PBPC-supported high-dose therapy including total body irradiation should be investigated further for patients with low-grade NHL while they are in first remission.

Adult↗
PubMed1996

[Radiochemotherapy of non-small-cell bronchial carcinoma. A report of experience].

PURPOSE: To investigate the survival of patients with inoperable non-small-cell lung cancer treated with combined radiochemotherapy. Frequency of local progression versus systemic dissemination after radiotherapy respectively radiochemotherapy. Extend of the toxicity of a combined modality treatment. PATIENTS AND METHODS: 60 inoperable patients (42 M0- and 18 M1-stage) with non-small-cell lung cancer who had received combined radiochemotherapy (RT+CT) were examined retrospectively. Different drugs or drug combinations were used. The sequence of radiotherapy and chemotherapy also differed. The survival was compared to that of another group of patients who had received at least 50 Gy with definitive radiotherapy at the same period of time (RT: N = 135). The Karnofsky performance index (KPI) was on an average of 80% in both groups. The primary of patients with systemic disease was treated by radiation when it became symptomatic or when it showed an evident progression. RESULTS: The two investigated treatment groups were comparable regarding KPI, histology, stage, tumor dose and age. The survival was significantly better when chemotherapy was added to radiotherapy. The median survival times in months were as follows: M0: RT 10.6/RT+CT 14.7; M1: RT 6.0/ RT+CT 9.3. Local tumor control was the major problem with or without chemotherapy (local progression of about 70% in both groups). The toxicity of radiochemotherapy was acceptable (bone marrow toxicity WHO-grade 4: 10.5%: nausea WHO-grade 4: 3%). CONCLUSION: In the absence of medical contraindications and with a KPI of at least 70% a combined radiochemotherapy in patients with inoperable non-small-cell lung cancer seems to be possible even if high radiation doses are used. Randomized studies are necessary to prove the impact on survival of an additional chemotherapy.

Adult↗
PubMed1996

Growth-state-dependent radiation-induced expression of the proto-oncogene c-fos in NIH 3T3 cells.

Expression of the proto-oncogene c-fos in response to ionizing radiation has been observed in some but not all cell lines tested. Here we report on delayed, transient c-fos expression in NIH 3T3 cells induced by 60Co gamma rays in the dose range 2-5 Gy. Induction of c-fos was significantly increased in cells irradiated in the density-arrested quiescent state compared to irradiation in the exponential growth phase. The enhancement correlated with the transition to quiescence as measured by the proliferation markers, proliferating cell nuclear antigen and bromodeoxyuridine. The observation of growth-state-dependent expression of c-fos after irradiation might indicate a functional relationship between c-fos and growth control in the DNA damage response, e.g. a potential role of c-fos in the control of replicative proteins.

3T3 Cells↗
PubMed1995

Estimation of pneumonitis risk in three-dimensional treatment planning using dose-volume histogram analysis.

PURPOSE: Investigations to study correlations between the estimations of biophysical models in three dimensional (3D) treatment planning and clinical observations are scarce. The development of clinically symptomatic pneumonitis in the radiotherapy of thoracic malignomas was chosen to test the predictive power of Lyman's normal tissue complication probability (NTCP) model for the assessment of side effects for nonuniform irradiation. METHODS AND MATERIALS: In a retrospective analysis individual computed-tomography-based 3D dose distributions of a random sample of 46/20 patients with lung/esophageal cancer were reconstructed. All patients received tumor doses between 50 and 60 Gy in a conventional treatment schedule. Biological isoeffective dose-volume histograms (DVHs) were used for the calculation of complication probabilities after applying Lyman's and Kutcher's DVH-reduction algorithm. Lung dose statistics were performed for single lung (involved ipsilateral and contralateral) and for the lung as a paired organ. RESULTS: In the lung cancer group, about 20% of the patients (9 out of 46) developed pneumonitis 3-12 (median 7.5) weeks after completion of radiotherapy. For the majority of these lung cancer patients, the involved ipsilateral lung received a much higher dose than the contralateral lung, and the pneumonitis patients had on average a higher lung exposure with a doubling of the predicted complication risk (38% vs. 20%). The lower lung exposure for the esophagus patients resulted in a mean lung dose of 13.2 Gy (lung cancer: 20.5 Gy) averaged over all patients in correlation with an almost zero complication risk and only one observed case of pneumonitis (1 out of 20). To compare the pneumonitis risk estimations with observed complication rates, the patients were ranked into bins of mean ipsilateral lung dose. Particularly, in the bins with the highest patient numbers, a good correlation was achieved. Agreement was not reached for the lung functioning as a paired organ. CONCLUSIONS: Realistic assessments for the prediction of radiation-induced pneumonitis seem to be possible. In this respect, the implementation of DVH-analysis in 3D planning could be a helpful tool for the evaluation of treatment plans.

Dose-Response Relationship, Radiation↗
PubMed1995

External radiotherapy of pituitary adenomas.

PURPOSE: To evaluate therapeutic outcome and side effects of radiotherapy in pituitary adenomas as sole or combined treatment. METHODS AND MATERIALS: Retrospective analysis of 138 patients (74 male, 64 female) irradiated for pituitary adenoma from 1972 to 1991 was performed. Mean age was 49.7 years (15-80 years). Regular follow-up (in the mean 6.53 +/- 3.99 years) included radiodiagnostical [computed tomography (CT), magnetic resonance imaging (MRI), x-ray], endocrinological, and ophthalmological examinations. Seventy patients suffered from nonfunctional pituitary adenoma, 50 patients suffered from growth-hormone producing adenomas, 11 had prolactinomas, and 7 patients had adrenocorticotropic hormone (ACTH) producing pituitary adenomas. In 99 patients surgery was followed by radiotherapy in case of suspected remaining tumor (invasive growth of the adenoma, assessment of the surgeon, pathologic CT after surgery, persisting hormonal overproduction). Twenty-three patients were treated for recurrence of disease after surgery and 16 patients received radiation as primary treatment. Total doses from 40-60 Gy (mean: 45.5 Gy) were given with single doses of 2 Gy 4 to five times a week. RESULTS: Tumor control was achieved in 131 patients (94.9%). In seven patients, recurrence of disease was diagnosed in the mean 2.9 years (9-98 months) after radiotherapy and salvaged by surgery. A statistically significant dose-response relationship was found in favor of doses > or = 45 Gy. Ninety percent of the patients with hormonally active pituitary adenomas had a benefit from radiotherapy in means of complete termination (38%) or at least reduction (52%) of hormonal overproduction. Partial or complete hypopituitarism after radiotherapy developed, depending on hormonal axis, in 12 (prolactin) to 27% (follicle-stimulating hormone FSH) of patients who had not already had hypopituitarism prior to radiation. Two out of 138 patients suffered reduction of visual acuity, which was, in part, related to radiotherapy. Both therapeutic effects and side effects occurred after a latency period of 3 months up to 9 years. CONCLUSION: We conclude that radiotherapy of pituitary adenomas, using modern treatment planning techniques, is effective and safe. To achieve optimal tumor control, doses of 45-48 Gy (conventionally fractionated) should be applied.

Adenoma↗
PubMed1995

Comparison between the alkaline unwinding technique and neutral filter elution using CHO, V79 and EAT cells.

Induction and repair of DNA strand breaks were measured in X-irradiated CHO, V79 and EAT cells using either the alkaline unwinding or the neutral filter elution techniques. After irradiation on ice, the cells were incubated at 37 degrees C for various times to allow for repair. The repair curves obtained were quite similar and the fast initial decline was always characterized by a half-time of 6-8 min and the final slow phase by a half-time of about 200 min independently of the technique used. The curves were found to differ only in the relative fraction of damage repaired during the fast or slow phase. From the similarity of the half-times it is concluded that the fast phase recorded by alkaline unwinding reflects the repair of single-strand breaks but also the repair of fast rejoining double-strand breaks. Comparing the known ratio of induced single- and double-strand breaks with the measured ratio of fast and slowly rejoining strand breaks as derived from the kinetics, it can be further concluded that the slow phase measured by alkaline unwinding covers the repair of both slowly rejoining double strand breaks as well as slowly rejoining single strand lesions.

Animals↗
PubMed1995

Comparison of proliferating cell nuclear antigen (PCNA) staining and BrdUrd-labelling index under different proliferative conditions in vitro by flow cytometry.

PC10 is a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The staining pattern in immunochemistry depends on fixation and detergent extraction treatment. The aim of this study was to validate the flow cytometric PCNA assay against Bromodeoxyuridine-labelling index (BrdUrd-LI) under different proliferative conditions in vitro. Expression of PCNA in methanol fixed cells with, and without, prior detergent extraction with EDTA/Triton was compared to BrdUrd-labelling index in NIH-3T3 fibroblasts and human Caski tumour cells in exponential phase and under confluent conditions. Serum stimulation and serum starvation conditions were studied. The results for BrdUrd-LI and PCNA-index after extraction showed good correlation for 3T3 fibroblasts and for Caski cells, with some differences for serum withdrawn Caski cells. There was no correlation between the number of cells that were positive for PCNA without extraction and BrdUrd-LI. Spheroid cells with G1-DNA-content showed an almost synchronous recruitment and progression through the cell cycle after trypsination and replating. Tightly bound PCNA paralleled this synchronicity whereas total PCNA did not change significantly. The results demonstrate that immunochemical detection of non-extractable PCNA-index gives similar results as compared with BrdUrd-labelling index under different proliferative conditions in vitro for different monolayer cell lines, whereas without extraction PCNA does not correlate with BrdUrd-LI in these fast growing cell lines due to its long half-life. PCNA expression parallels the progression through the cell cycle in V79 spheroids, a primitive model of tumour growth.

Animals↗
PubMed1995

[The problem of radiogenic and chemotherapy-induced mucositis of the mouth and and oropharynx exemplified by accelerated radiochemotherapy with carboplatin in patients with inoperable squamous epithelial carcinomas of the head-/neck area. Heidelberg experiences].

Despite numerous treatment measures mucositis of the mouth and pharynx due to radiochemotherapy frequently remains refractory to therapy. In most cases high doses of pain medications are till required. However, mucositis as a strong early reaction may be controllable by limiting cancer therapy. Within the current framework of accelerated radiochemotherapy with carboplatin, 50 patients with inoperable squamous cell carcinomas of the head and neck were followed from 1992 to 1994. Acute toxicity was documented from the first through eighth week after starting therapy. From the fifth week on, the degree of mucositis found was > 3 (WHO scale) in 24 patients. The extent of mucositis in 5 patients required interrupting therapy for 10 days on average. In 14 cases the average stay in hospital had to be prolonged by 10.2 days because of severe inflammation. In all, the average duration of mucositis after the end of the therapy amounted to 9.6 weeks. Twenty patients required bypass feedings with transnasal stomach tubes or percutaneous gastrostomy (PEG) tubes that were later removed. In addition, the incidences of dysphagia, xerostomia, hoarseness, skin reactions, nausea or vomitus and myelotoxicity were recorded. Descriptions of the supportive care concepts used at the University of Heidelberg are given and the supportive care concepts available scientific literature is updated.

Adult↗
PubMed1995

[The belly-board technic for the sparing of the small intestine. Studies on positioning accuracy taking into consideration conformational irradiation technics].

BACKGROUND: The immobilization error of patients positioned on the open table-top device in prone position as well as the movement of the small bowel out of the pelvis by this positioning technique was determined. The positioning error is of special importance for the 3-dimensional treatment planning for conformational radiotherapy. PATIENTS AND METHODS: The positioning error was determined by superpositioning 106 portal films with the corresponding simulator films from 21 patients with carcinoma of the rectum who-received 3D-planned conformational radiotherapy (3-field technique with irregular blocks). The movement of the small bowel out of the pelvis was studied by comparing simulator films after barium swallow in supine and open table-top position as well with 3D-treatment plans of the same patient in both positions in 3 cases. RESULTS: The positioning error along the medio-lateral, dorso-ventral and cranio-caudal axis was 1.4/0.6/1.8 mm and the standard deviation 4.4/6.8/6.3 mm, respectively. In comparison to the supine position more rotation errors in the sagittal view were observed (37% and 9% respectively) with a median of 5.1 degrees. Six out of 22 patients showed no adhesions of the small bowel and a complete movement out of the treatment field was achieved. 14 out of 16 Patients with adhesions revealed a partial movement of the small bowel out of the treatment field. Comparing 3D-treatment plans in both positions again demonstrated a marked reduction of the irradiated small bowel volume with the use of the open table-top device. CONCLUSIONS: The open table-top device positioning technique is a simple and cheap positioning support to reduce small bowel obstructions by radiation therapy of pelvic and retroperitoneal tumors. For the radiation treatment planning the data suggest a safety margin to compensate positioning errors of approximately 1.5 cm referring to the 95% confidence interval.

Administration, Oral↗
PubMed1994

Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma.

For patients with advanced-stage or poor-prognosis malignant lymphoma, high-dose therapy with peripheral blood progenitor cell (PBPC) support may become a first-line treatment. The duration of severe cytopenia in this setting is inversely related to the number of PBPCs autografted. In a retrospective analysis, we therefore looked for factors influencing the yield of PBPCs in 61 patients (16 with high-grade and 29 with low-/intermediate-grade non-Hodgkin's lymphoma [NHL], and 16 with Hodgkin's disease) who received cytotoxic chemotherapy and filgrastim (R-metHuG-CSF, 300 micrograms/d; median, 4.2 micrograms/kg/d; range, 2.7 to 6.6 micrograms/kg/d; subcutaneously). Sixteen patients had active disease, while 45 were in partial remission (PR) or complete remission (CR) after conventional therapy. A median of three leukaphereses (range, one to 10) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 0.03 to 31.1 x 10(6)). Previous cytotoxic chemotherapy and irradiation adversely affected the yield of CD34+ cells. Each cycle of chemotherapy is associated with an average decrease of 0.2 x 10(6) CD34+ cells/kg per leukapheresis in nonirradiated patients, while large-field radiotherapy reduces the collection efficiency by an average of 1.8 x 10(6)/kg CD34+ cells. The collection efficiency was also significantly lower in patients with Hodgkin's disease. However, except for one, all had been previously irradiated. In contrast, age, sex, disease status, bone marrow involvement during mobilization, and the time since the last chemotherapy or radiotherapy were not significantly related to the collection efficiency. Following high-dose conditioning therapy, 42 patients were autografted with filgrastim-mobilized PBPCs. Hematological recovery (neutrophils > or = 0.5 x 10(9)/L and an unsupported platelet count > or = 20 x 10(9)/L) within 2 weeks was observed in patients autografted with > or = 2.5 x 10(6) CD34+ cells/kg. In seven patients, the quantity of CD34+ cells reinfused was below this threshold. They required a median of 17 days (range, 11 to 34) and 31 days (range, 13 to 141) for neutrophil and platelet recovery, respectively. If autografting with PBPCs in malignant lymphoma with poor prognosis is being considered, mobilization and harvesting should be planned early after initial diagnosis to avoid exhaustion of hematopoiesis by cumulative toxicity.

Adolescent↗
PubMed1994

Influence of the positioning error on 3D conformal dose distributions during fractionated radiotherapy.

The influence of patient immobilization error on 3D planned conformal radiation therapy in tumors of the thorax and pelvis was studied. The mean positioning error in 43 patients with carcinomas of the thorax and pelvis undergoing 3D conformal radiotherapy (laser supported alignment, no immobilization device) was measured. A total of 194 portal films were superposed with the corresponding simulator radiographs according to anatomic landmarks and using a subtrascope. x-, y- and z-axis deviation was determined within a coordinate system. Using specialized software including Fourier transformation the mean positioning error was employed to recalculate the dose distributions of all cases under the influence of random (Gaussian) immobilization uncertainty. The mean two-dimensional positioning error using the data from all patients was 5.5 (+/- 3.7) mm. The distribution was Gaussian. Dose volume histograms (DVHs) of each patient with and without consideration of positioning uncertainty were compared on the base of tumor control probability estimations (TCP) using published DVH reduction and TCP algorithms. Inclusion of the positioning error resulted in a mean decrease in TCP (given as the difference between the TCP assuming no positioning error and the TCP modified by the positioning error) of 2% in a series of esophagus carcinomas and of 5% in the prostate carcinomas when looking at gross tumor volume (GTV), only. Planning target volume (PTV) exhibited a relative decrease in TCP of 5% and 11%, respectively.

Algorithms↗
PubMed1994

Hepatotoxicity in irradiated nephroblastoma patients during postoperative treatment according to SIOP9/GPOH.

This report describes liver toxicity in the risk group qualifying for combined postoperative irradiation and chemotherapy according to SIOP9/GPOH and diagnosed between January 1989 and June 1992 in hospitals participating in the GPOH studies (German Pediatric Oncology Hematology Group). Of 269 Wilms' tumor patients receiving postoperative treatment, 58 had abdominal irradiation (local SIOP, Stages II N+ and III standard histology [SH, n = 42]; and local Stages II and III, unfavorable histology [UH, n = 16]). Age was between 6 months and 22 years. Parallel to abdominal irradiation the patients were treated with polychemotherapy of differing combination depending on surgical stage and histology. All of them received actinomycin D (ACT D) and vincristine. However, ACT D was given according to protocol for standard histology Stage II and III in a dose of 15 micrograms/kg on 5 consecutive days and as single injection of 30 micrograms/kg in Stage IV standard and in unfavorable histology. For 37/58 children the major part (> 50%) of the liver was within the irradiation portals and 28/37 had whole liver irradiation. Doses ranged between 12 and 22.5 Gy and in 9 children parts of the liver received additional irradiation up to a total of 30 Gy. Eleven of 58 children (18%) developed hepatotoxicity and 4 of them veno-occlusive disease (VOD). Liver toxicity in irradiated patients occurred at a median of 6.5 weeks after start of postoperative treatment. The rate of toxicity was 4/14 versus 7/23 in patients receiving > 20 versus < 20 Gy to the major part of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Conservative treatment of breast cancer: modified irradiation technique for women with large breasts.

Seven patients with large, pendulous breasts received external beam irradiation to the whole breast (50 Gy in 25 fractions plus boost) after lumpectomy. A special breast holding mask was shaped for each patient. Three-dimensional treatment plans and dose-volume histograms of the same patient with and without a mask were compared. Day-to-day variance was checked. This technique provides improvements in dose homogeneity, reproducibility, and sparing of normal tissues. Cosmetic outcome at present is good.

Breast↗
PubMed1994

Influence of cisplatinum and 5-fluorouracil on the oral mucosa.

In a prospective study we examined the effect of preoperative chemotherapy with cisplatinum and 5-fluorouracil (5FU) in 40 patients with a carcinoma of the oral cavity. Histopathological grading, cell kinetic and immuno-histochemical parameters of the mucosa were determined at two different locations. Prior to therapy histological dysplasias "close" to the tumour were observed in the mucosa of 75% of the patients. Dysplastic changes of the mucosa "far" from the tumour were also found in more than one third of the patients. Our results show that more advanced dysplasias improve under the influence of preoperative systemic chemotherapy only temporarily. Moreover, new dysplasias which appeared during chemotherapy and persisted after its termination are probably induced.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

A modified computer-assisted colorimetric microtitre assay (MTT) to assess in vitro radiosensitivity of V79, CaSki, HeLa and WiDr cells.

The non-clonogenic MTT assay, based on the reduction of a tetrazolium salt to a purple formazan precipitate by living cells, was modified and a new procedure of analysis is proposed. The colorimetric assay could be performed semi-automatically using microtitre plate reader connected to a personal computer. Data are processed and plotted with a customized program. To ensure that both control and irradiated microtitre plates contain exponentially growing cells at the time of analysis, the calculation of relative survival is based on a series of well-defined cell numbers initially seeded. To make the two endpoints of non-clonogenic and clonogenic assays comparable, i.e. counting of living cells versus counting of colonies, radiation-induced progression delay was incorporated into the calculation. Radiation-induced cell killing and progression delay could be determined in a single analysis, but in an independent way. X-ray survival curves were generated for V79, CaSki, WiDr and HeLa cells using the non-clonogenic and a standard clonogenic assay. Using the linear-quadratic formula, the resulting parameters alpha, beta and the mean inactivation dose were not significantly different. The described assay is a feasible and reproducible technique for determination of cellular survival, which may be able to incorporate progression delay. The equivalence to a clonogenic survival assay could be proven.

Animals↗
PubMed1994

Effect of chronic alcohol consumption on the morphology of the oral mucosa.

Chronic alcohol consumption is a major risk factor for oral and pharyngeal cancer. Besides other mechanisms a toxic effect of ethanol and/or its metabolite acetaldehyde on the oral mucosa and resulting increased cell regeneration seem to play an important role in tumor promotion. In the present study the effect of chronic ethanol consumption on the morphology of the oral mucosa of 40 male wistar rats that had been fed nutritionally adequate liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrates for 6 months was investigated. Morphometric analysis showed that in the ethanol rats the size of the basal cell nuclei of the oral mucosa from the floor of the mouth, the edge of the tongue and the base of the tongue were significantly enlarged (p < 0.001). The size of the basal cell layer in these rats was increased, and the stratification of the cells was altered. The percentage of cells in the S-phase of the cell cycle was significantly higher in the ethanol-fed rats (p < 0.01). Mean epithelial thickness of the mucosa from the floor of the mouth was significantly reduced in the ethanol rats (p < 0.01). In conclusion, the reported findings indicate, that chronic ethanol consumption causes oral mucosal atrophy associated with hyper-regeneration, which may result in an enhanced susceptibility of the mucosal epithelium toward chemical carcinogens.

Alcohol Drinking↗
PubMed1994

Sequential high-dose therapy with peripheral-blood progenitor-cell support in low-grade non-Hodgkin's lymphoma.

PURPOSE: To evaluate the feasibility of a sequential high-dose therapy with peripheral-blood progenitor-cell (PBPC) support in patients with follicular lymphoma. PATIENTS AND METHODS: Since July 1991, we have included 30 patients (17 men and 13 women) with a median age of 41 years (range, 26 to 55) in the study. At the time of study entry, 17 patients were in first and six in second or higher remission. Another six patients had relapse of disease and one had tumor progression. PBPC were collected during filgrastim-supported leukocyte recovery following high-dose cytarabine (ara-C)/mitoxantrone (HAM). RESULTS: A median of two leukaphereses (range, one to seven) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 2.9 to 23.7 x 10(6). A distinct population of B-lymphoid progenitors (CD34+/CD19+) was not detectable in the autografts, and the content of CD19+ B cells was remarkably low, comprising a median of 0.07% of the mononuclear cells. Using the polymerase chain reaction (PCR) assay for the major breakpoint regions (MBR) of the bcl-2/immunoglobulin H (IgH) translocation, 22 patients had autografts positive for the t(14;18) translocation, whereas seven patients had PCR-negative transplants. The autograft of one patient could not be assessed. Following myeloablative therapy, hematologic recovery was rapid without cytokine support. The median times to reach a platelet count > or = 20 x 10(9)/L and neutrophil count > or = 0.5 x 10(9)/L were 11 and 13 days, respectively. Nonhematologic toxicity was moderate. Twenty-nine patients were alive in remission after a median follow-up duration of 6 months (range, 1 to 18). Of 22 patients autografted with t(14;18)-positive harvests, 11 had PCR-detectable cells in bone marrow and/or peripheral blood as long as 16 months posttransplantation. In contrast, six patients became PCR-negative between 3 and 16 months after reinfusion. Follow-up examinations with PCR data for the remaining five patients are not yet available. CONCLUSION: Conversion to PCR negativity in patients autografted with PCR-positive harvests suggests that the myeloablative regimen is effective and that any reinfused t(14;18)-positive cells may not be sustained. Because conventional chemotherapy provides no cure, we believe that high-dose therapy including total-body irradiation (TBI) should be explored in these particularly radiosensitive lymphomas.

Adult↗