Summary:Chemo-and radiotherapy may have injurious effects on developing teeth. In this long-term follow-up study among poor-risk neuroblastoma (NBL) survivors our aims were: (1) to assess both the type and extent of the side-effects of the anticancer treatment on tooth development; and (2) to develop an index for expressing total damage to the permanent dentition. We studied the dental development from panoramic radiographs (PRG) of 18 long-term survivors treated under the age of 6 years with high-dose (HD) chemotherapy and autologous stem cell transplantation (ASCT) for poor-risk NBL. The myeloablative therapy was either HD chemotherapy and fractionated total body irradiation (TBI) of 10-12 Gy (TBI group, n = 10) or HD chemotherapy only (non-TBI group, n = 8). A defect index (DeI) was developed to describe the damage to the permanent dentition. The DeI was also tested in 18 healthy adolescents. All NBL patients had disturbances in dental development including short roots, arrested root development, microdontia and tooth aplasia. After TBI, 9/10 patients had very severe root defects, in contrast to none in the non-TBI group. All children in the TBI group had 2-12 (mean 6.6) missing permanent teeth, while 2/5 in the non-TBI group (3/8 excluded due to young age) had two and four missing permanent teeth, respectively. Microdontia was found at equal frequency in both groups. The mean value of the DeI was 70.0 (range 28-117) in the TBI group, 15.2 (range 4-34) in the non-TBI group (P Ͻ 0.001, Mann-Whitney U test) and 1.8 (range 0-15) in healthy adolescents. Disturbances in dental development may compromise occlusal function in poor-risk NBL patients after ASCT, especially when TBI is included in the conditioning regimen. Long-term dental follow-up and rehabilitation is required.

Summary:We studied the use of autologous bone marrow transplantation (ABMT) as treatment for acute myeloid leukemia (AML) in adults up to age 60. We used a preparative regimen of busulfan 16 mg/kg plus etoposide 60 mg/kg and bone marrow purged with 100 g/ml of 4-hydroperoxycyclophosphamide (4HC). We treated 50 first remission patients; there were two treatmentrelated deaths and 13 relapses. With median follow-up of 6.8 years (minimum 4.5) disease-free survival (DFS) is 70%, relapse rate 27% and overall survival 72%. Patients with favorable cytogenetics had DFS 78% and relapse 18% whereas unfavorable patients had DFS 63% and relapse rate 35%. For 25 patients in second or third remission there were five treatment-related deaths and seven relapses. DFS is 52% and relapse rate 35%. None of six patients with primary refractory AML had long-term disease control. These data support the use of ABMT with an intensive preparative regimen and purged bone marrow as a highly effective treatment for adults with AML. Keywords: ABMT; AML; 4HC During the past decade there have been a number of improvements in the treatment of young adults with acute myeloid leukemia. All-trans retinoic acid (ATRA) has been identified as an important new agent in the treatment of acute promyelocytic leukemia. 1 High-dose Ara-C (HDAC) has been confirmed as superior to standard-dose Ara-C for post-remission therapy. 2 HDAC has been identified as especially helpful in the favorable cytogenetic groups with t(8; 21) and inversion 16q. 3 However, the majority of young adults with AML lacking favorable prognostic factors still fare poorly with conventional chemotherapy. Even with the use of repeated courses of HDAC post-remission therapy, only 20-25% of these patients will remain in long-term remission. 2 Experience with allogeneic bone marrow transplantation demonstrates that intensive therapies can lower the relapse rate and improve disease-free survival (DFS) for young adults with AML. 4 Furthermore, studies comparing preparative regimens have demonstrated the principle that more intensive preparative regimens can lower the relapse rate. 5 However, in the allogeneic transplant setting, these improvements in disease control have been offset by increases in treatment-related mortality (TRM). The use of targeted radiation through radioimmunoconjugates has produced very promising results and may allow this impasse to be broken. 6 Although allogeneic transplantation consistently produces improved DFS when compared to conventional chemotherapy, this treatment is limited by donor availability and by the 25% TRM which raises the question as to whether reserving allogeneic transplant as a salvage therapy would be an equal or better strategy.Autologous bone marrow transplantation (ABMT) has been actively investigated as an alternative way to improve outcome for AML patients. The treatment is attractive because of the potential for broad use in adults up to and perhaps beyond age 60 and because of relatively low TRM. Because of the absence of graft-versus-host ...

We studied the efficacy of a two-step approach to autologous stem cell transplantation for patients with advanced acute myeloid leukemia. Step 1 consisted of consolidation chemotherapy using cytarabine 2000 mg/m(2) twice daily for 4 days plus etoposide 40 mg/kg by continuous infusion over the same 4 days. Peripheral blood stem cells were collected under granulocyte colony-stimulating factor (G-CSF) stimulation during recovery from this chemotherapy. Step 2, autologous stem cell transplantation, utilized the preparative regimen of oral busulfan 16 mg/kg followed by etoposide 60 mg/kg i.v. During step 1, there were no treatment-related deaths among 28 patients, but two patients did not proceed to transplantation because of failure of mobilization. A median CD34+ dose (x10(6)/kg) of 13.6 was collected. Of 26 patients undergoing autologous transplant, there was one treatment-related death and 12 relapses. With a median follow-up of 5.4 years, 5 year event-free survival (EFS) of all patients entered is 54%. The most important prognostic factor was cytogenetic changes. All seven patients with t(15,17) remained in long-term remission whereas EFS for other patients was 38%. We conclude that this two-step approach to autologous transplantation produces excellent stem cell yields, allows a high percentage of patients to receive the intended therapy, and provides effective treatment.

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.