Empiric prednisone therapy for pulmonary toxic reaction after high-dose chemotherapy containing carmustine (BCNU).

STUDY OBJECTIVE: To determine pretreatment factors that predict for pulmonary toxic reactions after high-dose chemotherapy containing carmustine (BCNU) and to determine the utility of prednisone in preventing pulmonary toxic reactions. DESIGN: Retrospective review. SETTING: Tertiary care referral center. PATIENTS: Forty-five patients with relapsed or refractory lymphoma and 27 patients with breast cancer with normal cardiopulmonary function were treated with one of two high-dose combination chemotherapeutic regimens containing the same dose of BCNU. MEASUREMENTS: Recorded pretreatment patient characteristics included previous chemotherapy or radiation therapy, history of pulmonary metastases, history of chronic obstructive pulmonary disease, and history of smoking. Spirometry and single-breath carbon monoxide diffusing capacity (DCO) were obtained before and after high-dose chemotherapy. INTERVENTIONS: Patients were treated with prednisone for a 5% or more drop in postchemotherapy DCO whether or not symptoms were present. RESULTS: Fifty-nine patients were evaluable. No pretreatment characteristic predicted for declines in pulmonary function postchemotherapy. The FEV1/FVC ratio did not change significantly after high-dose chemotherapy, but the DCO decreased 12.1% (p < 0.001). Of the 59 evaluable patients, 30 were treated with prednisone for declines in postchemotherapy DCO. Sixteen (53%) of these 30 patients were asymptomatic. The DCO increased 10.3% in patients treated with prednisone compared with a decrease of 2.3% in patients not treated (p = 0.017). There was no statistically significant difference in FEV1/FVC in patients treated with prednisone compared with those not treated. Regression analysis of pretreatment characteristics, type of high-dose chemotherapy received, and treatment with prednisone identified only treatment with prednisone as a significant variable in predicting an increase in DCO (p = 0.03; regression coefficient = +11.5%, SE = +/- 5.2%) after high-dose chemotherapy containing BCNU. CONCLUSIONS: High-dose BCNU-containing chemotherapeutic regimens cause decreases in DCO that are often asymptomatic and likely represent subclinical pulmonary toxic reactions. Pretreatment clinical parameters cannot predict which patients will manifest pulmonary toxic reactions after high-dose chemotherapy. Empiric treatment with prednisone will reverse chemotherapy-induced decreases in DCO. Earlier institution of glucocorticoids for evidence of pulmonary dysfunction is recommended.

Eosinophilia after allogeneic bone marrow transplantation using the busulfan and cyclophosphamide preparative regimen.

Eosinophilia may complicate allogeneic bone marrow transplantation (BMT) after treatment with preparative regimens that include total body irradiation (TBI). This complication is of uncertain significance and has not been reported after treatment protocols which do not contain TBI. We reviewed our experience using busulfan and cyclophosphamide (CY), instead of TBI, as the preparative regimen for allogeneic BMT to study the incidence and relationship to graft-versus-host disease (GVHD) of post-treatment eosinophilia. Fifty-five consecutive patients receiving busulfan 16 mg/kg and CY 120 mg/kg for the treatment of leukemia were reviewed. All patients received non-T cell-depleted, HLA-matched sibling or unrelated donor marrow 2 days after chemotherapy was complete. Cyclosporine (CYA) and methylprednisolone were given to prevent GVHD. Thirty-nine patients surviving 100 days post-transplant were evaluated; 11 (28%) patients developed eosinophilia (defined as an absolute eosinophil count of > 500 x 10(6)) after transplant. Only 2 patients were still taking methylprednisolone at the onset of eosinophilia. At the onset of eosinophilia 5 of these 11 patients (45%) and GVHD that worsened within 2 months. In the other 6 patients (55%), GVHD was not present initially but developed in all 6 patients at a median of 4 months after the onset of eosinophilia. We conclude that eosinophilia can complicate allogeneic BMT not preceded by TBI and that it often heralds the onset of worsening of, or de novo, GVHD.

Survival after ABO-incompatible allogeneic bone marrow transplant after a preparative regimen of busulfan and cyclophosphamide.

The use of an ABO-incompatible donor for BMT after total body irradiation (TBI) has no adverse effect on engraftment, incidence of GVHD or survival when donor erythrocytes and plasma are depleted from the infused marrow. The outcome of ABO-incompatible BMT following a non-TBI-containing preparative regimen has not been as well studied. We therefore performed a retrospective review of consecutive patients undergoing allogeneic BMT for myeloid leukemia after treatment with high-dose busulfan and cyclophosphamide (BUCY) between January 1984 and January 1993. Of the 199 evaluable patients, 100 had AML or myelodysplastic syndrome, 30 of which were ABO-incompatible, and 99 had CML, 35 of which were ABO-incompatible. All patients undergoing transplant received erythrocyte and plasma-depleted marrow but 14 major ABO-incompatible patients also underwent plasma exchange before transplant. T cell-depletion and purging techniques were not employed. All records were reviewed for prognostic factors including patient age, sex, diagnosis, remission status at the time of transplant, and incidence and severity of acute and chronic GVHD. Compatible and incompatible patients with myeloid leukemia did not differ with respect to age, sex, remission status of disease at the time of transplant or incidence of GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

G-CSF post-autologous progenitor cell transplantation: a randomized study of 5, 10, and 16 micrograms/kg/day.

G-CSF is routinely administered after autologous bone marrow or peripheral blood progenitor cell transplantation to enhance neutrophil engraftment. However, many different doses of G-CSF have been described with no clear consensus on the most cost-effective dose. We performed a prospective randomized trial examining the efficacy of three different doses of G-CSF post-autologous transplant (5, 10, or 16 micrograms/kg/day). Fifty-seven consecutive patients with breast cancer (n = 30), non-Hodgkin's lymphoma (n = 16), Hodgkin's disease (n = 6), multiple myeloma (n = 2), acute leukemia (n = 2), and testicular cancer (n = 1) were randomized, with 19 patients enrolled in each of the three treatment groups. All patients underwent a high-dose chemotherapy preparative regimen and received an autologous peripheral blood progenitor cell (PBPC) transplant (without bone marrow), with G-CSF beginning on day 0. There was no difference in time to neutrophil engraftment among the three treatment groups (mean 10.2 to 10.8 days). There is a trend towards earlier platelet engraftment in the patient group receiving 5 microgram/kg/day of G-CSF. The total cost of G-CSF by dose group was $2900, $4400, and $6500 per patient. We conclude that there was no advantage to the use of higher doses of G-CSF after autologous transplantation, and that lower doses are associated with lower costs.

Clinical status of the new cytoprotective agent, amifostine.

In summary, the data presented and reviewed at this symposium provide a strong rationale for the use of amifostine as a cytoprotective agent. Amifostine has been shown to reduce morbidity in cancer patients receiving radiation and chemotherapy without compromising the antineoplastic activity of the cancer therapies employed. Amifostine has been investigated extensively and appears particularly effective with cisplatin and cyclophosphamide, which operate via direct binding to the active species of these alkylating agents. It may also have a role in the protection of normal hematopoietic stem cells during bone marrow purging prior to bone marrow transplantation. Finally, amifostine may act synergistically with hematopoietic growth factors (ie, G-CSF) to protect and accelerate the recovery of hematopoietic stem cells exposed to high doses of radiation.

High-dose busulfan and cyclophosphamide followed by autologous bone marrow transplantation and/or peripheral blood progenitor cell rescue for metastatic breast cancer.

High doses of combination alkylating agents have shown promise in the treatment of breast cancer but are complicated by significant toxicity. Busulfan and cyclophosphamide (BuCy) is a high-dose combination alkylating agent regimen that is well-tolerated when given for hematologic malignancy. We prospectively studied the effects of BuCy followed by autologous bone marrow transplant (ABMT) or peripheral blood progenitor cell (PBPC) rescue in 21 patients with metastatic breast cancer who had responded to either standard chemotherapy or radiotherapy. The mean patient age was 44 years. Nine patients were either estrogen- or progesterone-receptor positive, ten were negative, and two were unknown. Fourteen patients had local recurrence, ten had bone metastases, six had visceral disease, and two had a nonlocal soft tissue recurrence. Busulfan 16 mg/kg and cyclophosphamide 120 mg/kg (BuCy2) was given and followed by either ABMT, PBPC rescue, or both. Grade III to IV extramyeloid toxicity occurred in 6 (29%) patients. One patient died of hepatic venoocclusive disease but there was no other treatment-related mortality. Pulmonary infiltrates with hypoxia of uncertain origin developed in 2 patients after discharge. Of the 10 patients with measurable disease, 4 had complete responses, and 3 had partial responses to high-dose therapy for a total response rate of 70%. The estimated 2-year disease-free survival is 25% (95% CI = 6% to 44%). Our study found BuCy to be a well-tolerated preparative regimen for ABMT in the treatment of patients with metastatic breast cancer.

Clinical decision-making: acute myelogenous leukemia in first complete remission.

SUMMARY: Most patients with acute myelogenous leukemia achieve complete remission but are not cured with chemotherapy alone. Bone marrow transplantation is an alternative to chemotherapy, but there is controversy as to which patients benefit from transplantation. KEY POINTS: Outcome can be predicted by, and therapy tailored to, specific prognostic factors such as age and karyotype. Younger patients with good-risk karyotypes such as t(8;21) and inv16 have a long-term disease-free survival rate of 75% or more with chemotherapy alone. Patients with poor-risk karyotypes have a survival rate less than 10% with chemotherapy alone and may benefit from bone marrow transplantation, which is associated with cures in up to 50% of patients. Most patients do not have a compatible donor for allogeneic transplantation. High-dose chemotherapy and autologous bone marrow transplantation is an option for patients with no marrow donor, and has cure rates of as high as 50%. Patients with intermediate-risk karyotypes generally have a survival rate between 20% and 50% with chemotherapy alone. It is uncertain if allogeneic or autologous bone marrow transplantation offers any additional advantage in this group.

Hemorrhagic ascites secondary to endometriosis.

Ascites secondary to endometriosis is extremely uncommon, but curable. We therefore report hemorrhagic ascites in a young woman with this disorder, and provide a literature review and summary of clinical features. The pathogenesis of ascites in this setting is unknown.