Breed differences over time and heritability estimates for production and reproduction traits of dairy goats in the United States.

To aid in improvement of breeding programs for production and reproduction traits of US dairy goats, breed differences over time were documented and genetic parameters were estimated. Data were from herds with ≥2 breeds (Alpine, LaMancha, Nubian, Oberhasli, Saanen, or Toggenburg), but only purebred data were analyzed. Three kidding periods were examined: 1976 through 1984, 1985 through 1994, and 1995 through 2005. Univariate repeatability mixed models were used to estimate least squares means by kidding period-breed and genetic parameters for milk, fat, and protein yields, combined fat and protein yield, fat and protein percentages, protein:fat ratio, age at first kidding, and kidding interval. Trends across kidding periods were favorable for most yield traits for all breeds but generally unfavorable for reproduction traits. Saanens had the highest milk (1,063 to 1,125 kg) and protein yields (31 to 33 kg). Nubians had the highest fat yields (37 to 40 kg) and lowest milk yields (791 to 851 kg). Oberhaslis had the lowest fat (31 to 33 kg) and protein (23 to 27 kg) yields. Alpines had the largest increase in milk yield (7.4%); Oberhaslis had the largest increase in protein (17.4%) and combined fat and protein (13.2%) yields. Combined fat and protein yield was higher for Nubians, Saanens, and Alpines (65 to 72 kg) than for LaManchas, Toggenburgs, and Oberhaslis (53 to 67 kg). Nubians had the highest fat (4.7 to 4.8%) and protein (3.6 to 3.8%) percentages. Only Nubians increased in fat percentage (2.1%); protein percentage increased most for Toggenburgs (7.4%) and Alpines (7.1%). Protein:fat ratio was highest for Toggenburgs (0.84 to 0.89) and lowest for Nubians (0.76 to 0.81), but Nubians had the largest increase in protein:fat ratio (6.6%). Saanens were oldest at first kidding (509 to 589 d), and Toggenburgs and LaManchas generally were youngest (435 to 545 d); age at first kidding increased most for Alpines (21.8%) and LaManchas (21.6%). Kidding intervals generally were shorter for Oberhaslis, LaManchas, and Nubians (350 to 377 d) than for Toggenburgs, Alpines, and Saanens (373 to 387 d). Kidding interval increased most for Nubians (3.9%) and Saanens (3.8%) and decreased only for Oberhaslis (5.4%). Heritability estimates across breeds were 0.35 for milk and fat yields, 0.37 for protein yield and protein:fat ratio, 0.36 for combined fat and protein yield, 0.52 for fat percentage, 0.54 for protein percentage, 0.23 for age at first kidding, and 0.05 for kidding interval. Genetic selection within breed is feasible for production and reproduction traits of US dairy goats.

Reproductive status of Holstein and Jersey cows in the United States.

Reproductive information since 1995 from the USDA national dairy database was used to calculate yearly Holstein and Jersey means for days to first breeding after calving (DFB), 70-d nonreturn rate, conception rate (CR), number of breedings per lactation (NB), interval between first and last breedings during the lactation, days to last breeding after calving (DLB), pregnancy rate (PR), calving interval (CI), and interval between consecutive breedings. Data were from nearly 20 million breedings during >8 million lactations of >5 million cows in >23,000 herds. Means were also calculated for some traits by parity and breeding number for both breeds and by geographical region and synchronization status for Holsteins. The DFB declined for Holsteins from 92 d in 1996 to 85 d in 2007; the trend in yearly differences was not as consistent for Jerseys. First- and all-breeding 70-d nonreturn rate declined 5 to 9 percentage units over time. First- and all-breeding CR declined 2 to 4 percentage units. The DFB were longer for later parities of Holsteins than for early parities. Second- and third-breeding CR were sometimes 1 to 2 percentage units above first-breeding CR for Holsteins but lower (1 to 7 percentage units) for Jerseys. The CR within breeding number declined across parities for both breeds. The NB increased by 0.3 to 0.4 breedings over time but remained constant (2.5 or 2.6 breedings) across parities for Holsteins and increased (from 2.2 to 2.4 breedings) for Jerseys. Holstein DFB were fewest in the Northwest (78 d) and greatest in the Mountain region (92 d). Regional CR was highest for the Northeast and Southwest (33%) and lowest for the Southeast (26%); NB was fewest for the Northeast (2.3) and greatest for the Southeast (2.7). Mean DLB was fewest for the Southwest (127 d) and greatest for the Mountain region (157 d); CI was shortest for the Southwest (406 d) and longest for the Mideast (434 d). Mean PR was highest for the Southwest (28.3%) and lowest for the Mideast and Southeast (22.2%). Use of timed artificial insemination following synchronized estrus appears to have reduced DFB, lowered CR, and increased NB while reducing DLB and CI. However, synchronized breeding was not a primary cause of Holstein regional differences for reproductive traits. Since 2002, phenotypic performance for CR, DLB, and CI as well as genetic merit for daughter PR have stopped their historical declines and started to improve.

Genetic and environmental factors that affect gestation length in dairy cattle.

Genetic and environmental factors that might affect gestation length (GL) were investigated. Data included information from >11 million parturitions from 1999 through 2006 for 7 US dairy breeds. Effects examined were year, herd-year, month, and age within parity of conception; parturition code (sex and multiple-birth status); lactation length and standardized milk yield of cow; service sire; cow sire; and cow. All effects were fixed except for service sire, cow sire, and cow. Mean GL for heifers and cows, respectively, were 277.8 and 279.4 d for Holsteins, 278.4 and 280.0 d for Jerseys, 279.3 and 281.1 d for Milking Shorthorns, 281.6 and 281.7 d for Ayrshires, 284.8 and 285.7 d for Guernseys, and 287.2 and 287.5 d for Brown Swiss. Estimated standard deviations of GL were greatly affected by data restrictions but generally were approximately 5 to 6 d. Year effects on GL were extremely small, but month effects were moderate. For Holstein cows, GL was 2.0 d shorter for October conceptions than for January and February conceptions; 4.7 and 5.6 d shorter for multiple births of the same sex than for single-birth females and males, respectively; 0.8 d longer for lactations of < or =250 d than for lactations of > or =501 d; and 0.6 d shorter for standardized yield of < or =8,000 kg than for yield of > or =14,001 kg. Estimates for GL heritability from parities 2 to 5 were 33 to 36% for service sire and 7 to 12% for cow sire; corresponding estimates from parity 1 were 46 to 47% and 10 to 12%. Estimates of genetic correlations between effects of service sire and cow sire on GL were 0.70 to 0.85 for Brown Swiss, Holsteins, and Jerseys, which indicates that those traits likely are controlled by many of the same genes and can be used to evaluate each other. More accurate prediction of calving dates can help dairy producers to meet management requirements of pregnant animals and to administer better health care during high-risk phases of animals' lives. However, intentional selection for either shorter or longer GL is not recommended without consideration of its possible effect on other dependent traits (e.g., calving ease and stillbirth).

Rejection with hemodynamic compromise: objective evidence for efficacy of photopheresis.

BACKGROUND: Photopheresis therapy (photo) has been advocated as a therapy to improve outcome after recalcitrant or severe rejection, but objective evidence of a beneficial effect has been elusive. This study examined the hypothesis that photo provides protection against rejection, rejection with hemodynamic compromise (HC), and death from rejection after cardiac transplantation. METHODS: Between 1990 and 2003, 36 adult patients (from 343 adult transplant recipients) received at least 3 months of photo (2-day treatment every 3 to 6 weeks for a target of 18 months) after HC rejection (n = 12), recurrent/recalcitrant rejection (n = 20), or as prophylaxis in the presence of anti-donor antibodies (n = 4). Survival and risk factors were examined by analysis using multivariate hazard function modulated renewal function. RESULTS: Patients selected for photo were at greater risk for rejection (p < 0.0001) and HC rejection (p < 0.0001) than non-photo patients. After 3 months of photo therapy, rejection risk was decreased (p = 0.04). More importantly, the hazard for subsequent HC rejection or rejection death was significantly reduced toward the risk-adjusted level of lower-risk non-photo patients (p = 0.006). CONCLUSIONS: This study provides objective evidence that photo reduces the risk of subsequent HC rejection and/or death from rejection when initiated for patients with high rejection risk. Photopheresis is recommended as an important therapeutic modality after rejection with hemodynamic compromise, although further studies are needed to define the precise mechanism of the effect and the potential for benefit in other patient sub-sets.

The Cancer Informatics Infrastructure: a new initiative of the National Cancer Institute.

OBJECTIVES: To inform oncology nurses about the National Cancer Institute (NCI) Cancer Informatics Infrastructure initiative that will transform cancer care through more effective and efficient information exchanges among all involved in cancer research. DATA SOURCES: Published articles and reports from the NCI pertaining to the initiative. CONCLUSIONS: Clinical trials represent the primary mechanism for evaluating promising new strategies to prevent, diagnose, and treat cancer. Advances in information technology and the exponential increase in the use of the internet are providing unprecedented opportunities to streamline the operation and administration of the clinical trials the NCI supports. IMPLICATIONS FOR NURSING PRACTICE: The revitalized system will be more flexible and inclusive and will facilitate input from oncology nurses and others with a commitment to improving cancer care.

Alternating MOPP and ABVD chemotherapy plus mantle-field radiation therapy in patients with massive mediastinal Hodgkin's disease.

PURPOSE: To evaluate the efficacy and toxicity of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy plus mantle-field radiation therapy in the treatment of patients with massive mediastinal Hodgkin's disease of any stage. PATIENTS AND METHODS: Eighty patients presented with Hodgkin's disease and a mediastinal mass greater than one third the greatest chest diameter on chest radiograph. Patients were staged and treated with MOPP alternated with ABVD chemotherapy for a total of six cycles. Patients then received 10 Gy mantle-field radiation therapy delivered to the original extent of disease followed by 25 to 35 Gy to the residual abnormalities. RESULTS: The complete response (CR) rate was 89%. With a median follow-up duration of 10 years, disease-free survival of the complete responders is 78% at 15 years and overall survival is 75% at 15 years. For patients with stage I or II disease, disease-free survival was 76% at 15 years and overall survival was 79%; for those with stage III or IV disease, disease-free survival was 82% at 15 years and overall survival was 64%. Age, stage, sex, B symptoms, number of extranodal sites, lactate dehydrogenase (LDH) levels, erythrocyte sedimentation rate, and platelet count did not influence treatment outcome. Treatment-related pneumonitis was noted in 16% of patients (fatal in one), mainly in those older than age 35 years who received total doses of radiation therapy greater than 42 Gy. Fertility is more often preserved with MOPP/ABVD therapy than with MOPP chemotherapy and there appears to be less pulmonary and cardiac disease than with ABVD chemotherapy. Two patients have developed second solid tumors within radiation ports and one relapsed patient developed acute leukemia after MOPP salvage therapy. CONCLUSION: MOPP/ABVD followed by mantle-field radiation therapy is an effective treatment for all stages of Hodgkin's disease that present with a large mediastinal mass. Our data suggest that the large mediastinal mass is a more dominant determinant of prognosis than Ann Arbor stage or other clinical prognostic factors.

Variance component estimation and multitrait genetic evaluation for type traits of dairy goats.

Covariance components for final score and 13 linear type traits of dairy goats were estimated by multitrait REML using canonical transformation with an animal model. Data were 10,932 type appraisals from 1988 through 1994 from herds with > or = 40 appraisals. Heritabilities were estimated as 0.27 for final score, 0.52 for stature, 0.29 for strength, 0.24 for dairyness, 0.38 for teat diameter, 0.21 for rear legs, 0.32 for rump angle, 0.27 rump width, 0.25 for fore udder attachment, 0.25 for rear udder height, 0.19 for rear udder arch, 0.25 for udder depth, 0.33 for suspensory ligament, and 0.36 for teat placement. Genetic correlations of linear type traits and final score were positive except for dairyness (-0.15) and teat diameter (-0.10); the largest correlations with final score were 0.66 for fore udder attachment, 0.44 for rear udder arch, 0.36 for rump width, and 0.30 for strength. The largest positive correlation among linear traits was 0.63 for stature and rump width; the largest negative correlation was -0.51 for strength and dairyness. Multitrait evaluations were calculated with data from all herds. Correlations between PTA calculated with animal and sire models ranged from 0.44 to 0.70 for bucks that had a PTA with a reliability of > or = 30%.

NCI's cancer information systems--bringing medical knowledge to clinicians.

The National Cancer Institute's computerized information systems have been designed to help physicians cope with the information explosion by translating the medical literature into usable forms. Systems developed by the NCI's International Cancer Information Center provide access to a comprehensive source of bibliographic citations on cancer research (the CANCERLIT database) and to current, peer-reviewed syntheses of state-of-the-art clinical information on cancer (the PDQ database). This article describes how the PDQ databases were developed and are kept up-to-date, and how physicians and other health professionals can access PDQ and other NCI information by computer and fax.

Diffuse small noncleaved-cell, non-Burkitt's lymphoma in adults: a high-grade lymphoma responsive to ProMACE-based combination chemotherapy.

PURPOSE: To review the efficacy of cyclophosphamide, doxorubicin, etoposide, methotrexate with leucovorin, and prednisone (ProMACE)-based combination chemotherapy programs in the treatment of patients with diffuse small noncleaved-cell non-Burkitt's lymphoma. PATIENTS AND METHODS: Thirty-three patients with diffuse small noncleaved-cell non-Burkitt's lymphoma were accrued: eight with localized disease were treated with modified ProMACE-mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) plus involved-field radiation therapy, and 25 with advanced-stage disease were treated with ProMACE/MOPP flexitherapy (n = 8), ProMACE-MOPP (n = 9), or ProMACE-cytarabine, bleomycin, vincristine, and methotrexate with leucovorin (CytaBOM) (n = 8). The median follow-up duration is 10 years. RESULTS: All eight patients with localized disease achieved a complete response, none have relapsed, and one died of intercurrent illness. Among patients with advanced-stage disease, five of eight (63%) flexitherapy-treated patients, six of nine (67%) ProMACE-MOPP-treated patients, and eight of eight (100%) ProMACE-CytaBOM-treated patients achieved a complete response. If the two ProMACE-MOPP-based groups are considered together, disease-free and overall survival rates at 15 years are projected at 61% and 35%, respectively. In contrast, only one patient has relapsed from a ProMACE-CytaBOM-induced complete remission, and overall survival of ProMACE-CytaBOM-treated patients (88%) is significantly higher than that for flexitherapy and ProMACE-MOPP (P2 = .04). CONCLUSION: Adult patients with diffuse small non-cleaved-cell non-Burkitt's lymphoma may be effectively treated with regimens that are effective in other aggressive lymphomas (eg, diffuse large-cell lymphoma).

Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure.

PURPOSE: The study was undertaken to evaluate clinical prognostic factors, probability of response to therapy, duration of response, and overall survival of patients with Hodgkin's disease relapsing from a chemotherapy-induced complete remission. PATIENTS AND METHODS: Study population comprised 107 patients with Hodgkin's disease treated with combination chemotherapy at the National Cancer Institute who relapsed after achieving a complete remission. RESULTS: Half of the relapses occurred within the first year of achieving complete remission; among patients in remission 5 years or longer, only 4% relapsed. The overall survival of the relapsed patients is projected to be 17% at 20 years, calculated from the date of relapse. Primary treatment regimen, presence of B symptoms, stage, sex, liver involvement, pleural involvement, marrow involvement, and histologic subtype did not affect the survival of relapsed patients. Only age at diagnosis (older or younger than 30 years) and length of initial remission (shorter or longer than 1 year) made a significant impact on survival. Patients whose initial remission was longer than 1 year had significantly higher complete response rates to salvage therapy, significantly more durable second remissions, and significantly longer survival than patients whose initial remission was shorter than 1 year. Survival beyond 11 years from relapse of patients with long initial remissions was 24%; for those with short initial remissions, 11% (P2 = .027). Despite the fact that with salvage therapy, patients with long initial remission had an 85% complete response rate to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) with a disease-free survival of 45% at 20 years, acute leukemia and other treatment-related complications combined to lower the survival rate of this more favorable subset. CONCLUSIONS: These data with conventional-dose salvage therapy provide results for comparison with novel salvage approaches including myeloablative therapy with autologous marrow or peripheral-blood stem-cell support.

The calculation of actual or received dose intensity: a comparison of published methods.

Two recent reports of the same combination chemotherapy program, cyclophosphamide, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, bleomycin, and prednisone (ProMACE-CytaBOM), in similar subsets of patients with advanced-stage aggressive-histology lymphoma used two different methods to report the actual dose-intensity (DI) data. One method treats DI as a property of a particular cycle of treatment within the entire population that received that cycle. The other treats DI as a characteristic of a particular patient's entire treatment course. We have applied both methods to the same set of data and provide evidence that the latter method is preferable for at least two reasons: (1) it more accurately reflects actual DI by clearly incorporating the duration of the actual treatment course and, thus, can be used to compare the administration of same or related regimens to distinct patient populations; and (2) it allows assignment of a numerical value to an individual patient's treatment course or a group of patients' treatment courses such that DI can be examined for its impact on treatment outcome just like any other prognostic factor. The observed differences in treatment outcome between the Southwest Oncology Group (SWOG) and National Cancer Institute (NCI) studies are not clearly related to differences in distribution of clinical prognostic factors in the two study populations. The differences in methods of reporting DI prohibit evaluation of the influence of dose-related variables on outcome in the two studies. Adoption of a standard method of calculating and reporting DI data would facilitate evaluation of the prognostic significance of DI.

Treatment-related morbidity in patients with lymphoma.

The evolution of effective therapies for lymphoma has led to cures for many patients. In addition to the acute morbidity associated with cytotoxic therapy, significant delayed treatment-related effects have been identified. Complications include immunologic, cardiovascular, pulmonary, thyroid, and gonadal dysfunction as well as the development of second neoplasms. These complications results from tissue injury caused by the administration of radiation or chemotherapy, persistent immunologic deficits related to the underlying malignancy or its therapy, and complications of surgical staging and splenectomy. Disease or treatment-related immunosuppression and the mutagenic effects of therapy appear to predispose these patients to an increased risk of second cancers. This article reviews data from the recently published literature on these issues.

Treatment of advanced-stage Hodgkin's disease: alternating noncrossresistant MOPP/CABS is not superior to MOPP.

One hundred twenty-five assessable patients with advanced-stage Hodgkin's disease were randomized to receive mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or MOPP alternating with lomustine (CCNU), doxorubicin, bleomycin, and streptozocin (CABS). The median follow-up is 7.7 years. The complete response rate was 60 of 66 MOPP-treated patients (91%) and 54 of 59 MOPP/CABS-treated patients (92%) (difference not significant). The level of the disease-free survival curve at longest follow-up is 65% for MOPP-treated patients and 72% for MOPP/CABS-treated patients (difference not significant). The overall survival at 12 years is projected at 68% for MOPP-treated patients and 54% for MOPP/CABS-treated patients (difference not significant). Thus, there were no significant differences in efficacy between MOPP and MOPP/CABS. However, MOPP/CABS was more emetogenic than MOPP, and four MOPP/CABS-treated patients went on to develop secondary acute leukemia. No MOPP-treated patients developed leukemia. High initial erythrocyte sedimentation rate (ESR) and high platelet counts adversely affected treatment outcome. MOPP-treated patients who received greater than 81% of the projected dose intensity of vincristine over the first three cycles had significantly improved disease-free survival rates over those receiving less than 81%. MOPP/CABS-treated patients who received greater than 82% of the projected dose intensity of vincristine had significantly better overall survival than those who received less than 82%. Disease-free survival on both arms was significantly better in patients who received greater than 84% of the projected dose intensity of all agents. The effect of dose intensity was particularly apparent in patients with poor prognostic factors where those who received greater than 84% of the projected dose intensity of all agents had significantly improved disease-free and overall survival.

Radiation therapy versus combination chemotherapy in the treatment of early-stage Hodgkin's disease: seven-year results of a prospective randomized trial.

The study population included 136 patients with stage IA, IB, IIA, IIB, or IIIA1 Hodgkin's disease. The median follow-up is 7.5 years. Among the 30 patients with peripheral IA disease, all patients achieved a complete response (CR) with radiation therapy, and no patient has relapsed. Patients of other stages were randomized to receive radiation therapy or mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). Among the 51 patients randomized to receive radiation therapy, 49 (96%) achieved complete remission, 17 (35%) have relapsed, and 10 (20%) have died. Fifty-two of the 54 (96%) assessable patients randomized to receive MOPP obtained CRs, seven (13%) have relapsed, and four (7%) have died. The projected 10-year disease-free survival of patients randomized to receive radiation therapy is 60%; for those randomized to receive MOPP, it is 86% (P2 = .009 in favor of MOPP). The projected 10-year overall survival for patients randomized to radiation therapy is 76%, and for MOPP-treated patients it is 92% (P2 = .051 in favor of MOPP). When the randomized patients with massive mediastinal disease or stage IIIA1 disease were excluded from the analysis, the disease-free (67% for radiation v 82% for MOPP) and overall survival (85% for radiation v 90% for MOPP) were not significantly different between the two arms. Subset analysis showed significant superiority of MOPP in the treatment of the following patient groups: stage IIIA1 or massive mediastinal disease, no B symptoms, initial erythrocyte sedimentation rate greater than 20 mm, four or more sites of disease, and younger than age 40 years. Preliminary analysis of this ongoing study shows that MOPP chemotherapy is at least as effective as radiation therapy in the treatment of the specific groups of early-stage Hodgkin's disease patients randomized. The final assessment of these two diverse treatment options will depend largely on the long-term survival and the incidence of early- and late-treatment complications for which patients are continuing to be observed.

Treatment of advanced-stage massive mediastinal Hodgkin's disease: the case for combined modality treatment.

In the initial series of 198 patients treated at the National Cancer Institute (NCI) with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy for Hodgkin's disease, a review of presenting chest radiographs available on 192 of these patients showed 49 patients with mediastinal masses greater than one third the greatest posteroanterior chest diameter. Five patients had stage IIB disease, and 44 had stage III or IV disease. Thirty-five (71%) patients achieved a complete remission with MOPP chemotherapy. Fourteen (40%) of the complete responders relapsed, but four of these achieved durable remissions in response to subsequent therapy. Thirty (61%) patients have died (14 induction failures, nine relapsed patients, seven complete responders in remission). Thus, with a median follow-up of 20 years (range, 15 to 23), the overall survival for the group is 39%, and the disease-free survival for the complete responders is 60%. A subset of 10 patients received mantle radiation therapy after maximal response to MOPP. One of these patients failed to achieve complete remission, but among the nine complete responders only one has relapsed. In contrast, 13 of 26 (50%) patients achieving a complete response to MOPP alone have relapsed (P2 = .0536). Although MOPP alone was not prospectively compared with MOPP plus radiation therapy in the treatment of advanced-stage massive mediastinal Hodgkin's disease in this series, the retrospective analysis shows a nearly significant difference in disease-free survival favoring combined modality treatment. The difference in tumor mortality between MOPP-treated (44%) and combined modality-treated patients (80%) was also nearly significant (P2 = .055). However, overall survival differences between patients treated with MOPP alone and those treated with combined modality therapy were not significantly different (P2 = 0.23) because of the mortality related to late complications of combined modality treatment.

Superiority of ProMACE-CytaBOM over ProMACE-MOPP in the treatment of advanced diffuse aggressive lymphoma: results of a prospective randomized trial.

One hundred ninety-three patients with stage II, III, or IV follicular large-cell, diffuse large-cell, diffuse mixed, immunoblastic, or diffuse small noncleaved-cell (non-Burkitt's) lymphoma were randomized to receive either cyclophosphamide 650 mg/m2 intravenously (IV), doxorubicin 25 mg/m2 IV, etoposide 120 mg/m2 IV on day 1, mechlorethamine 6 mg/m2 IV, vincristine 1.4 mg/m2 (no cap at 2 mg total dose) IV on day 8, prednisone 60 mg/m2 orally daily days 1 through 14, procarbazine 100 mg/m2 orally daily days 8 through 14, and methotrexate 500 mg/m2 IV on day 15 with leucovorin 50 mg/m2 orally every 6 hours for four doses beginning 24 hours after methotrexate with cycles repeated every 28 days (ProMACE-MOPP) or same day-1 treatment as ProMACE-MOPP plus cytarabine 300 mg/m2 IV, bleomycin 5 U/m2 IV, vincristine 1.4 mg/m2 (no cap at 2 mg total dose) IV, and methotrexate 120 mg/m2 IV on day 8, leucovorin 25 mg/m2 orally every 6 hours for four doses beginning 24 hours after methotrexate, and prednisone 60 mg/m2 orally daily days 1 through 14 with cycles repeated every 21 days (ProMACE-CytaBOM). Co-trimoxazole two double-strength tablets orally twice daily throughout the period of treatment was added to the ProMACE-CytaBOM regimen when an increased risk of Pneumocystis carinii pneumonia was found in the first 35 patients receiving this combination. Median follow-up is 5 years. Among the 99 patients treated with ProMACE-MOPP, 73 achieved a complete remission (CR) (74%), 30 complete responders have relapsed (41%), and 45 patients have died (45%), including two (2%) of treatment-related causes. Among the 94 patients treated with ProMACE-CytaBOM, 81 achieved a CR (86%), 22 complete responders have relapsed (27%), and 31 patients have died (33%). The complete response rate (P2 = .048) and survival (P2 = .046) were significantly higher for patients treated with ProMACE-CytaBOM. The mortality of ProMACE-CytaBOM treatment overall was six of 94 patients (6.4%). There was no treatment-related mortality among patients treated with prophylactic co-trimoxazole (n = 59). ProMACE-CytaBOM combination chemotherapy with co-trimoxazole prophylaxis is a safe and effective treatment for patients with aggressive histology malignant lymphoma and is superior to ProMACE-MOPP.