We reviewed the medical records of 44 adults with 50 consecutive episodes of thrombotic thrombocytopenia purpura (TTP) or hemolytic uremic syndrome (HUS) seen at the University of California, San Francisco affiliated hospitals during the past decade. Patients were treated according to a uniform plan in which initial therapy included daily large volume plasmapheresis using fresh frozen plasma. Patients not responding completely to initial therapy were treated with a salvage regimen including splenectomy, dextran, and corticosteroids. At the time of diagnosis, the lactate dehydrogenase (LDH) was elevated in 98% of cases, with a median value of 1,208 U/L. Other clinical features were present inconsistently, and only 34% of “TTP” episodes involved the classic pentad of hemolytic anemia, thrombocytopenia, neurologic disorders, noninfectious fever, and renal impairment. Primary treatment with plasma exchange produced complete remission in 56% (27 of 48) of the episodes. Previously splenectomized patients uniformly responded to plasma therapy (12 of 12). In patients not responding completely to primary therapy, salvage splenectomy produced complete responses in 81% (13 of 16) of the cases. The pattern of clinical response to therapy was consistent, with initial resolution of neurologic dysfunction (median, 3 days) followed by normalization of LDH levels (5 days) and platelet count (7 days). Normalization of renal function occurred significantly later (15 days). Although short-term responses to plasma therapy in human immunodeficiency virus (HIV)-seropositive patients did not differ from other patients, no HIV-positive patient survived more than 2 years from diagnosis of thrombotic microangiopathy (TMA). We conclude that the diagnosis of TMA requires a high degree of clinical suspicion and that the diagnostic criteria should consist of microangiopathic hemolytic anemia, thrombocytopenia, and an elevated LDH. Initial therapy with plasma exchange leads to disease control in the majority of cases, but an optimal treatment strategy requires the use of alternative methods if initial remission is transient or not achieved. Salvage therapy with splenectomy, steroids, and dextran is highly effective in this setting.

We treated 109 patients with adult acute lymphoblastic leukemia (ALL) diagnosed by histochemical and immunologic techniques. Patients were excluded only for age greater than 50 years and Burkitt's leukemia. Treatment included a four-drug remission induction phase followed by alternating cycles of noncrossresistant chemotherapy and prolonged oral maintenance therapy. Eighty-eight percent of patients entered complete remission. With a median follow-up of 77 months (range, 48 to 111 months), 42% +/- 6% (SEM) of patients achieving remission are projected to remain disease-free at 5 years, and disease-free survival for all patients entered on study is 35% +/- 5%. Failure to achieve remission within the first 4 weeks of therapy and the presence of the Philadelphia chromosome are associated with a 100% risk of relapse. Remission patients with neither of these adverse features have a 48% +/- 6% probability of remaining in continuous remission for 5 years. Patients with T-cell phenotype have a favorable prognosis with 59% +/- 13% of patients achieving remission remaining disease-free compared with 31% +/- 7% of CALLA-positive patients. Intensive chemotherapy may produce prolonged disease-free survival in a sizable fraction of adults with ALL. Improved therapy is needed, especially for patients with adverse prognostic features.

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Summary:We designed and implemented a new mitoxantronebased high-dose chemotherapy regimen to minimize pulmonary injury (seen in carmustine-based regimens) in patients with breast cancer. One hundred and ninetyone breast cancer patients (99 stage II/IIIA; 27 stage IIIB; 65 stage IV responsive to conventional-dose chemotherapy) were treated with high-dose chemotherapy (CTM) delivered over 4 days (cyclophosphamide (6 g/m 2 ), thiotepa (600 mg/m 2 ), and mitoxantrone (24-60 mg/m 2 )) followed by autologous hematopoietic stem cell rescue. Stage II/III patients received chest wall radiation and tamoxifen (if hormone-receptor positive) after CTM. The 5-year event-free survival (EFS) for stage II/IIIA patients with 10 or more involved axillary lymph nodes (n = 80) was 62 ؎ 12%. Hormone receptor-positive patients with 10 or more nodes did significantly better than negative patients. The EFS for stage IIIB patients at 5 years was 44 ؎ 19%; for stage IV patients at 5 years was 17 ؎ 10%. Stage IV patients achieving complete response in viscera and/or soft tissue prior to CTM did significantly better than those achieving a partial response. There were six (3%) treatment-related deaths including two due to diffuse alveolar hemorrhage. There were no episodes of delayed interstitial pneumonitis. There were six severe cardiac events in 91 patients (6.6%) but none after instituting mitoxantrone dose-adjustment in the final 100 patients. We conclude that CTM is associated with a low treatment-related mortality and little pulmonary toxicity. CTM produces excellent outcomes in stage II/IIIA patients with 10 or more involved axillary lymph nodes. Bone Marrow Transplantation (2000) 26, 257-268.

We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.