Nadir Leukocyte Count Research Articles

Profile of infections and outcome in high-risk febrile neutropenia: experience from a tertiary care cancer center in India

Objective of the present study was to describe the profile of infections in febrile neutropenia (FN) in acute leukemia and hematopoietic stem cell transplant (HSCT) with emphasis on response to therapy and outcome. In a prospective, observational single-institutional study, consecutive episodes of high-risk FN were enrolled over a 1½-year period. Uniform antibiotic policy and response criteria were used. Of the 200 episodes enrolled, acute leukemia induction comprised 40.5%, consolidation with high-dose cytarabine 22.5%, HSCT 29% (auto-HSCT 84%), and others 8% of the episodes, respectively. Microbiologically documented infections comprised 30% episodes, while bacteremia was documented in 26% episodes. Gram-negative isolates were more common (55.7%). Cefoperazone-sulbactam had the highest in vitro efficacy against Gram-negative rods. Carbapenem resistance was most prevalent among Acinetobacter spp. (80%) and Pseudomonas aeruginosa (50%). All Gram-positive cocci other than enterococci were susceptible to vancomycin, while 2/8 enterococci were resistant to it. Cefoperazone-sulbactam and amikacin were used as first-line antibiotics. Overall mortality was 8%. On multivariate analysis, mortality was associated with a nadir leukocyte count < 200/μl and an abnormal chest radiograph. Among high-risk FN patients, inspite of a high-level of resistance to antibiotics, a frontline regime containing cefoperazone-sulbactam could restrict the use of imipenem and resulted in an acceptable mortality of 8%.

Peripheral hematopoietic progenitor cell mobilization for autologous transplantation in hematologic malignancies

In this issue of the Revista Brasileira de Hematologia e Hemoterapia, Gabus et al.(1) are publishing an interesting article about hematopoietic progenitor cell mobilization for autologous transplantation in hematologic malignancies. Although the analysis was retrospective, they utilized the abundant statistical tools and compared two successive groups of patients with similar numbers and over similar periods, in order to compare patients in respect to the origin of the growth factor used, different brands in the first group and a specific growth factor (JP Filgen - Clausen filgrastim) in the second. First, it is worth noting some features of the profile of the service in which the mobilization was analyzed that performs a large number of autologous compared to allogeneic transplants (80% and 20% respectively) and a slight predominance of patients from the Uruguayan National Health System. The target collection of CD34+ cells was consistent with the literature. Some results should be mentioned and discussed: 1. The mobilizations were very effective with collections of the desired numbers of CD34+ cells using few leukapheresis procedures from most patients; 2. The 10% mobilization failure rate corroborates medical literature, both for the overall proportion, in respect to age and autologous transplantation and active disease. However, many patients with multiple myeloma had mobilizations even though characteristically these patients mobilize well, better than those with Hodgkin's lymphoma, for example. One possible explanation for this may be related to the chemotherapy used, melphalan, which used to be considered a single line chemotherapy before, but with significant negative impact on mobilization, much more than a number of other chemotherapy lines; 3. The strategy to try to collect from bad mobilizers in this series was very effective whether by repeating the mobilization (majority) or collecting cells directly from bone marrow; 4. Another important feature to be commented on is the relative small proportion of patients mobilized with filgrastim associated with chemotherapy (14.6%) as most were mobilized with growth factor alone (85.4%). As the paper states, the use of chemotherapy in combination with filgrastim is reserved for patients when difficulty in obtaining CD34+ cells is expected or when there is any additional benefit from chemotherapy, such as to better control the underlying disease. We believe that in vivo purging before mobilization will help patients to enter the autologous transplantation procedure closer to remission, even considering the higher cost (more growth factors, hospital, antibiotics, transfusions, etc) and the greater difficultly to obtain CD34+ cells. But this is still an open question in the medical literature; 5. A very important point to discuss is that Group B, i.e., those mobilized with Filgen JP (Clausen filgrastim) used a significantly lower amount of filgrastim but the quality of mobilization was similar, which may be more efficient in relation to the filgrastim used previously (Group A). Our group has been studying for several years, strategies to optimize the collection of hematopoietic progenitor cells from peripheral blood by apheresis, considering various parameters. Our first work was published in 2000,(2) when we had observed that shorter periods between chemotherapy, mobilization and recovery of total leukocytes, improve the collection in terms of fewer leukaphereses needed to obtain CD34+ cells. The parameter to begin apheresis was recovery after the nadir leukocyte count reached 1000 cells/mm3. Following that, in a study published in 2006,(3) we analyzed other parameters to predict the ideal time to start apheresis, in order to reduce the number of procedures. At that time, we began to use the same guideline that Gabus et al,(1) i.e., when the CD34+ count in peripheral blood reached 10 cells/mm3. We were able to demonstrate, through sequential daily blood cell and CD34+ counts, that the best day can be predicted by a formula that considers hemoglobin on the day of mobilization chemotherapy and the number of days between chemotherapy mobilization and when the CD34+ cell count in peripheral blood reached 10 cells/mm3. Thus, we discovered that we were collecting too early. Using this formula prospectively, we analyzed in terms of cohort, this new strategy of mobilization(4) and observed that this formula was useful in patients with lymphoma, but not with multiple myeloma. As we can see with these considerations above, this is an important issue that deserves to be further studied and published, thus supporting the initiative that Gabus et al.(1) had in publishing this article.

An analysis of a multiple-drug program in the treatment of patients with advanced breast cancer utilizing 5-fluorouracil, cyclophosphamide, and prednisone with or without vincristine

Ninety patients with advanced breast cancer received a polychemotherapeutic program composed of 5-fluorouracil, cyclophosphamide, and prednisone with or without vincristine as a control group in a series of four consecutive Phase II clinical trials of new drug programs. Objective regression rates were 59% without vincristine and 46% with vincristine. Projected mean length of regressions exceeds I year. Site of dominant disease, disease-free interval, or performance scale score (if score was 0, 1, or 2, ECOG scale) failed to influence response rates; decreasing response rates were noted as the length of time increased after menopause. No advantage existed in patients experiencing severe myelosuppression (nadir leukocyte count of less than 1,500/mn3, and appreciable response rates occurred without significant myelosuppression. The addition of vincristine to the regimen failed to increase the response rates, and only increased toxicity. The program as outlined is reasonably tolerable and effective for this group of patients with advanced breast cancer.

Chikungunya fever in Singapore: Acute clinical and laboratory features, and factors associated with persistent arthralgia

Background In Singapore, the first local outbreak of chikungunya was reported in January 2008, followed by a larger outbreak occurred in August 2008. During the initial outbreak period, a strict containment strategy was adopted and all chikungunya PCR-confirmed cases were isolated and hospitalised at the designated national outbreak management centre. Objectives To detail daily clinical and laboratory features of chikungunya cases during acute illness, and determine factors associated with persistent arthralgia at week 6. Study design Prospective cohort study of patients with PCR-confirmed chikungunya infection and hospitalised within 5 days of illness onset, from 1st August to 10th November 2008. Post-hospital discharge, patients were followed up at the specialist outpatient clinic, and assessed for arthralgia at week 6 of illness. Results Of the 97 patients in the study, the most common presenting symptoms were fever (89.7%) and arthralgia (87.6%). Mean nadir leukocyte and platelet counts were 3.5(SD 1.9) × 10 9/L and 165(SD 42) × 10 9/L respectively. Of the 39 patients who were evaluated at week 6, 14 (35.9%) had persistent arthralgia. Those with persistent arthralgia tended to be females ( p = 0.003), and had a lower peak creatinine level ( p = 0.036) than those without. Peak viral load ( p = 0.664), and duration of fever ( p = 0.056) and viremia ( p = 0.55) respectively, were not significantly different between those with persistent arthralgia and those without. Conclusions This study details the daily clinical and laboratory features of chikungunya patients during acute illness. Those with persistent arthralgia tended to be females, who had significantly lower peak creatinine level.

The use of bosentan and a prostacyclin analog in the treatment of primary pulmonary hypertension

early (range 3-7 fractions) due to minor marrow suppression or infectious complications. The mean (sd) nadir leukocyte count was 2.98 (1.34) x 10 and platelet nadir 114 (41) x 10. Seven (19%) required blood transfusion and only 2(5%) had serious infections as complications. Duration of TLI course was mean (sd) 62.8 (41.7) days. Mean (sd) rate of decline in FEV1 was 122.7 (21.6) mls/month before TLI and 25.1(7.7) mls/month after TLI, (difference in rate of decline 95% CI 48.2-146.7), p 0.0004 (students paired t-test). Total survival in the 37 treated recipients is median (range) 59 (6-146) months and the post TLI survival is 27 (0-93) months. TLI is a well tolerated treatment with only mild marrow suppression and a low incidence of serious infection. It results in a significant reduction in the rate of FEV1 decline in rapidly progressive BOS. TLI should form part of the immunosuppressive armoury in patients with aggressive BOS.

The tolerability and efficacy of total lymphoid irradiation (TLI) in the control of rapidly progressive bronchiolitis obliterans syndrome

Low dose radiotherapy (8 Gy in 10 fractions) to the lymphoid structures can be used as an adjunct to standard immunosuppressive therapy in progressive Bronchiolitis Obliterans Syndrome (BOS). Data on tolerability and efficacy of TLI is however limited. In our centre, 37 (16M:21F) recipients have received TLI for progressive BOS between 1988 and 2001. Mean (sd) recipient age was 37.6(12.7) years when they underwent 13 single, 12 bilateral and 12 heart-lung transplants. Baseline FEV1 was mean (sd) 2.60 (0.8)litres. BOS was diagnosed median (range) 18 (4 - 81) months after transplant. BOS grades at the time of TLI were BOS 1(7), BOS 2 (14), and BOS 3 (16). The mean (sd) FEV1 pre-TLI was 1.32 (0.57) litres. Twenty seven (73%) recipients successfully completed ≥8 fractions. Ten did not complete planned treatment: 2 died very early during TLI due to respiratory failure; 8 were stopped early (range 3-7 fractions) due to minor marrow suppression or infectious complications. The mean (sd) nadir leukocyte count was 2.98 (1.34) x 109 and platelet nadir 114 (41) x 106. Seven (19%) required blood transfusion and only 2(5%) had serious infections as complications. Duration of TLI course was mean (sd) 62.8 (41.7) days. Mean (sd) rate of decline in FEV1 was 122.7 (21.6) mls/month before TLI and 25.1(7.7) mls/month after TLI, (difference in rate of decline 95% CI 48.2-146.7), p=0.0004 (students paired t-test). Total survival in the 37 treated recipients is median (range) 59 (6-146) months and the post TLI survival is 27 (0-93) months. TLI is a well tolerated treatment with only mild marrow suppression and a low incidence of serious infection. It results in a significant reduction in the rate of FEV1 decline in rapidly progressive BOS. TLI should form part of the immunosuppressive armoury in patients with aggressive BOS.

Hemodialysis Neutropenia Correlates with a Decreased Filterability and an Increase in the Number of Cytoplasmic Actin Filaments in Peripheral Blood Neutrophils, Which Is Preceded by a Decrease in the Number of Surface Expression of L-Selectin

In order to clarify the precise cellular mechanism of hemodialysis neutropenia, we examined the changes in the viscoelasticity of peripheral blood neutrophils using both the micropore and the microchannel filtration methods, and the changes in the neutrophil surface expression of Mac-1, L-selectin and sialyl Lewis X and the cytoplasmic expression of the actin filaments using a flow cytometric analysis during a dialysis session. Five patients with chronic renal failure were selected who showed a nadir leukocyte count in peripheral blood at 30 min after the initiation of the dialysis session. The neutrophil count also reached a nadir at 30 min and thereafter returned to almost the predialysis level by 180 min. Both the micropore filtration time and the microchannel passage time, which reflect the viscoelasticity of the peripheral blood neutrophils, correlated inversely with the neutrophil count. At the nadir of neutropenia, the neutrophils were observed to have become both adhesive and viscoelastic. The actin filaments in the neutrophil cytoplasm gradually increased in number from the start of dialysis, reaching a peak level at 30 min, and thereafter decreasing to predialysis levels. The Mac-1 expression continuously increased up from 30 min until the end of dialysis. The L-selectin expression first decreased at 15 min, but thereafter returned to predialysis levels within 60 min. The SLe^x expression did not change throughout the course of the session. These results thus indicated the neutrophil counts during a dialysis session to inversely correlate with the viscoelasticity of the neutrophils expressed by the micropore filtration time or microchannel passage time, which possibly depends on the contents of cytoplasmic actin filaments. In addition, the shedding of L-selectin from neutrophil surface may also be involved in the first step of hemodialysis neutropenia.

Pharmacodynamics of prolonged oral etoposide in patients with advanced non-small-cell lung cancer.

This study was undertaken to investigate the pharmacodynamic relationship between etoposide drug levels on 21-day oral treatment courses and hematologic toxicities in patients with advanced non-small-cell lung cancer (NSCLC). Thirty-two patients with stage IIIB or IV NSCLC were treated with oral etoposide 50 mg/m2/d for 21 consecutive days in combination with cisplatin 100 mg/m2 on day 1. Treatment was repeated every 28 days for up to six courses. Patients had not received previous chemotherapy and had a performance status of 0 to 2. Patients were monitored weekly while on treatment for compliance with oral etoposide and toxicity, including complete blood cell counts, and a blood sample before the daily etoposide dose (drug trough levels). Etoposide concentrations were measured in the plasma by high-performance liquid chromatography (HPLC). Three patients achieved a complete response (CR) and 10 patients a partial response for an objective response rate of 41% (95% confidence interval, 24% to 58%). The median survival was 4 months (range, 1 to 23). Neutropenia was dose-limiting, and two patients died of neutropenic sepsis. Pharmacodynamic correlations for drug concentrations and hematologic toxicities were available for 27 patients and a total of 76 treatment courses, and correlations were significant for graded hematologic toxicity and nadir counts of leukocytes, neutrophils, hemoglobin, and platelets. The grade of infection (77 courses) was also related to drug levels. Using data from 27 initial courses, a pharmacodynamic model was developed to estimate the nadir leukocyte or neutrophil count (WBCn, ANCn) based on the pretreatment count (WBCp, ANCp) and the etoposide concentration (Ec) as follows: WBCn = 0.35 (1 + WBCp x e-1.12 x Ec) and ANCn = 0.32 (1 + ANCp x e-2.47 x Ec). Etoposide concentrations are related to the resulting hematologic toxicities. It is possible to predict nadir counts in the first course by a pharmacodynamic model. The above equations need to be validated prospectively and may be useful in future studies of prolonged oral etoposide.

A Phase I/II Trial of 5-Fluorouracil and Etoposide in Metastatic Colorectal Carcinoma

Twenty-two patients with metastatic colorectal carcinoma were treated in a Phase I-II study of combination therapy with 5-fluorouracil (5-FU) and etoposide (VP-16). Treatment consisted of weekly intravenous VP-16, 100-120 mg/M2, followed by 5-FU, 400-480 mg/M2, in 28-day cycles. Myelosuppression was the dose-limiting toxicity with a mean nadir leukocyte count of 3,600/mm3 and a mean nadir thrombocyte count of 101,000/mm3. There were no episodes of sepsis or bleeding. The tolerable dose for this regimen is VP-16, 110 mg/M2, and 5-FU, 440 mg/M2, weekly. A total of 63 cycles of chemotherapy were given. Although 10 patients had stabilization of disease, no partial or complete responses were documented. We conclude that there is no clinical support for the in vitro synergy observed with this combination. Further trials of this combination using this schedule in colorectal carcinoma are not indicated.

Evaluation of Menogaril in Patients with Metastatic Sarcomas and No Prior Chemotherapy Exposure

Menogaril, an anthracycline analog of nogalamycin, is reported to have greater cytotoxicity against certain malignant cell lines and less cardiotoxicity in rabbits than doxorubicin. To evaluate the possible therapeutic benefit of this drug, we studied menogaril in 21 patients with metastatic sarcomas who had received no prior chemotherapy. Menogaril was administered intravenously over 1 h every 3-4 weeks at a dose of 200 mg/m2 in 500 ml of 5% dextrose in water. One patient experienced a partial regression of pulmonary metastases from malignant fibrous histiocytoma of bone (response rate of 5% with 95% confidence interval of 0.1-23.8%). Two additional patients experienced minor reductions in tumor size. The remaining 18 patients had no improvement from menogaril. The median time to disease progression was 7 weeks in all patients treated. Toxicity was acceptable, consisting primarily of leukopenia with 12 patients (57%) and 19 patients (90%) developing nadir leukocyte counts less than 2000 and 3000/microL, respectively. Cardiac toxicity was not encountered; however, only seven patients received greater than or equal to 3 cycles of menogaril. We conclude that menogaril does not appear to be useful at this dose and schedule in the treatment of metastatic sarcomas despite the use of near maximal doses in patients with no prior chemotherapy exposure.

A phase I trial of dactinomycin intravenous infusion in patients with advanced malignancies.

Eighteen patients with advanced malignancies refractory to other forms of treatment were given dactinomycin (Act D) as continuous intravenous infusions. Their median age was 51 years (range, 36-67); their median performance status was 50 (range, 40-90) on the Karnofsky scale. Act D was administered continuously for 5 days, utilizing a central venous line and a perfusion pump. The starting dose was 0.1 mg/m2/24 hours X 5 days (total dose, 0.5 mg/m2) and was escalated according to a modified Fibonacci scale to 0.2, 0.33, and 0.5 mg/m2/24 hours X 5 days, respectively. Three, three, four, and eight patients were entered, respectively, in each dose level. Toxicities observed were: leukopenia in four patients (nadir leukocyte count less than 1000 cells/nm3 in one patient and 2000-3000 cells/mm3 in 3 patients); thrombocytopenia, with nadir platelet counts between 50,000 and 100,000 platelets/mm3 in 2 patients; stomatitis in four patients; and nausea in three patients. Vomiting was not observed during the infusions. Two patients may have had a radiation recall phenomenon. Blood count depression, nausea, and mucositis were transient, resolving after a few days. One patient at level IV died of sepsis, which was diagnosed on the fourth day of the infusion, before leukopenia intervened. No objective responses were seen. It was concluded that a higher dose of Act D can be given by continuous infusion than by a bolus injection; the authors recommended 0.5 mg/m2/day X 5 days (total dose, 2.5 mg/m2) for further studies.

High-dose cisplatin in patients with advanced malignancies.

A study was conducted to determine if cisplatin (CDDP) can be given at higher doses than usual, utilizing aggressive supportive measures. Twelve patients were entered into three dose levels of CDDP: level I, 180 mg/m2 given as a short infusion; level II, 220 mg/m2 also given as a short infusion; level III, 200 mg/m2 divided in five daily doses, each infused over 6 hours. In all cases, CDDP was dissolved and given in 250 ml of a 5% saline solution. For levels I and II, intravenous hydration with 200 to 250 ml/hour D5 1/2NS with potassium and magnesium supplements, was started 24 hours before therapy and continued for 3 to 4 days after, longer if nausea persisted. Mannitol was given before (25% solution, 50 ml bolus) and after (20% solution, 500 ml over 3 hours) CDDP. At level III hydration with the same intravenous (IV) fluids was begun the day before therapy and continued without interruption at 200 to 250 ml/hour for a minimum of 24 hours after the completion of the 5 days of chemotherapy. Each daily dose of CDDP was preceded by injection of mannitol (25% solution, 50 ml bolus) and accompanied by a 6-hour infusion of 1000 ml 20% mannitol. Three patients received five CDDP courses at level I; 4 patients, seven courses at level II; and 5 patients, seven courses at level III. Ototoxicity was dose-limiting in three patients at level II. Transient elevation of serum creatinine was seen following two courses at level I and two courses at level II. The renal impairment was asymptomatic in all cases; dialysis was not needed. At level II, leukocyte nadir counts between 1.0 and 2.0 X 10(3)/mm3 were seen following two courses and between 2.0 and 3.0 X 10(3)/mm3 following three courses. Platelet nadir counts below 50 X 10(3)/mm3 were recorded after four courses and between 50 and 100 X 10(3)/mm3 after one course. Nausea and vomiting occurred frequently, but were tolerable. At level III, myelosuppression was dose-limiting. Nadir leukocyte counts between 1.0 and 2.0 X 10(3)/mm3 followed four courses and between 2.0 and 3.0 followed one course. Nadir platelet counts below 50 X 10(3)/mm3 were seen after three courses; two patients required prophylactic platelet transfusions. Nadirs between 50 and 100 X 10(3) platelets/mm3 followed three further courses. Ototoxicity and nephrotoxicity did not occur at level III.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of lithium carbonate on chemotherapy-induced neutropenia and thrombocytopenia.

Lithium carbonate ameliorates neutropenia associated with cancer chemotherapy. The effect of lithium on platelet suppression has not, however, been well established. In the present study, five patients with ovarian carcinoma received daily lithium during alternate cycles of treatment with hexamethylmelamine, cyclophosphamide, adriamycin, and cis-platinum. Analysis of myelosuppression was performed on 24 paired consecutive cycles given at identical doses, one with and one without lithium. During lithium cycles, nadir leukocyte, neutrophil, and platelet counts were significantly higher (P less than 0.01, less than 0.01, less than 0.05 respectively) and the interval between treatments was shorter (P less than 0.01). One patient who has received 11 cycles of chemotherapy continues to receive 100% doses owing to the beneficial effect of lithium on chemotherapy-induced thrombocytopenia. Lithium was poorly tolerated by some patients because of either tremor or nausea and vomiting, in spite of nontoxic serum lithium levels. The amelioration of drug-induced platelet suppression as well as neutrophil suppression noted in this study suggests that lithium's effect on hematopoiesis is not limited to stimulation of neutrophil production. The ability of lithium to decrease chemotherapy-induced myelosuppression suggests that lithium administration may facilitate escalation of chemotherapy doses in selected patients.

The combined modality therapy of diffuse histology non-Hodgkin's lymphoma with cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) and total body irradiation

The combination of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) alternating with total body irradiation (TBI) has been shown earlier to be effective therapy in patients with malignant lymphoma who have received prior chemotherapy and/or radiation therapy. A limited institutional pilot study was therefore done by the Southwest Oncology Group between October 1977, and November 1978 to test the benefit of this program in previously untreated persons with Stages 3 and 4 diffuse histology non-Hodgkin's lymphoma. Eleven evaluable patients with the following histologies were treated: 7 poorly differentiated, 2 with histiocytic, 1 with mixed lymphoma and 1 with well-differentiated morphology. CHOP was given in the following manner: cyclophosphamide 400 Mg/M 2 IV day l, adriamycin 40 Mg/M 2 IV day 1, vincristine 2 mg IV day 1, and Prednisone 100 mg po daily × 5. Forty-five rad total body irradiation was delivered in three fractions on days 21, 23 and 25. Chemotherapy was repeated on day 42, etc., until four cycles of CHOP and three cycles TBI (135R) were delivered. Responses were seen in 8 11 patients (6 CR and 2 PR); 5 persons are currently alive and 6 are dead. Two of the living patients are alive with disease and the remainder are in unmaintained remission. Two persons died with no response and one died in complete remission of an unrelated illness. The median duration of remission is 15 months and the median survival for all patients is 48 months. The therapy was well tolerated with a mean nadir leukocyte count of 3,020 × 10 9/μ1 (range 1.2–5.5) and a mean nadir platelet count of 188 × 10 9/μl (range 016–270). As delivered, this program is capable of producing durable remissions and needs to be verified in a larger series of patients.

Prognostic significance of changes in serum transcobalamin levels in cancer patients with chemotherapy-induced granulocytopenia.

Serum transcobalamin (TC) levels were determined daily in 14 adults suffering from advanced nonhematological malignancies and hospitalized because of chemotherapy-induced leukopenia and fever. Even during the nadir leukocyte count, TCI and TCIII serum levels were normal or only slightly decreased indicating that bone marrow activity was not completely suppressed. A significant increase in serum TCII level was observed in all patients, with peak values occurring an average of 4.5 days from admission at a time when the median leukocyte count was 2,300/mm 3. Full white cell count recovery followed this peak TCII elevation within a mean of 5.5 days in all patients, coinciding with a fall in TCII levels to basal values. The rise in serum TCII level appears to be an early indicator for imminent bone marrow recovery in myelosuppressed patients.

The combined modality therapy of diffuse histology non-hodgkin lymphoma with combination chemotherapy and total body irradiation

The combination of cyclophosphamide, adriamycin, vincristine, and orednisone (CHOP) alternatina with total bodv irradiation (TBIl is effective therapy in patients with malignant lymphoma who have received prior chemotherapy and/or radiation therapy. 1 A limited institutional pilot study was done by the SWOG between January, 1977 and July, 1978 to test the benefit of this program in untreated persons with stages 3 & 4 non-Hodgkin lymphoma of diffuse histology. Thirteen patients were treated and are evaluable. Histologies included: seven with poorly differentiated, four with histiocytic and two with mixed lymphana. CHOP was given in the following manner: cyclophosphamide 40Omg/m* I.V. Dl, adriamycin 4Omg/m* I.V. Dl, vincristine 2mg I.V. Dl, and prednisone 1OCmg p.o. daily x 5. 45 Rads total body irradiation were delivered in 3 fractions on days 21, 23 and 25. Chemotherapy was repeated on 042, etc., until 4 cycles CHOP and 3 cycles TBI (135R) were delivered. Responses were seen in 9/13 patients and 8 remain alive. Four persons died with no response and one died in complete remission of an unrelated illness. The median duration of remission is in excess of 3 years and the median survival has not been reached. Therapy was well-tolerated with a mean nadir leukocyte count of 36OO/cu.mn. (Range 1200-7700) and a mean nadir platelet count of 109 (Range 032-270). The activity of this program may be superior to that reported for chemotherapy alone and warrants confirmation in a larger series of patients. The techniques employed and a detailed analysis will be presented.