Cynthia Aristei

BACKGROUND: In this study we tried to achieve successful transplantation in patients with acute leukemia with the use of hematopoietic stem cells from donors who shared only one HLA haplotype with the recipient (a "full-haplotype mismatch"). To prevent graft failure, large doses of T-cell-depleted hematopoietic stem cells were transplanted after a conditioning regimen of enhanced myeloablation and immunosuppression was administered to the recipient. METHODS: Forty-three patients with high-risk acute leukemia who were scheduled for transplantation received total-body irradiation, thiotepa, fludarabine, and antithymocyte globulin. The graft consisted of peripheral-blood progenitor cells that had been mobilized in the donor with recombinant granulocyte colony-stimulating factor and also, in 28 cases, bone marrow. Bone marrow from the donor was depleted of T lymphocytes by processing with soybean agglutinin and E-rosetting. T-cell depletion of peripheral-blood mononuclear cells was achieved by E-rosetting followed by positive selection of CD34+ cells. No post-transplantation prophylaxis against graft-versus-host disease (GVHD) was administered. RESULTS: In all the patients, full donor-type engraftment was achieved. In none of the patients who could be evaluated did acute or chronic GVHD develop. Regimen-related toxicity was minimal. Eleven of the 23 patients with acute lymphoblastic leukemia had a relapse, as did 2 of the 20 patients with acute myeloid leukemia. Transplantation-related mortality was 40 percent. After a median follow-up of 18 months (range, 8 to 30), 12 of the 43 patients were alive and free of disease. All surviving patients had a good quality of life. CONCLUSIONS: The main limitations of transplantation of bone marrow from donors who are matched with the recipient for only one HLA haplotype GVHD and graft failure - can be overcome. Since most patients have a relative with one haplotype mismatch, advances in this method will increase the availability of hematopoietic-cell transplantation as curative therapy for acute leukemia.

A retrospective analysis was conducted to evaluate the incidence of nodal failure in a subgroup of patients who had T1-T2 breast cancer and four or more positive nodes. Sixty-four 5 patients ranging in age from 29 to 73 years (median, 51) received conservative surgery followed by radiotherapy to the breast between November 1980 and May 1995. Adjuvant chemotherapy was administered to 56 patients, 27 of whom were also treated with tamoxifen, which was used alone in 5 patients. Three patients received no adjuvant treatment. Sixty-two patients are evaluable for regional node failure. There were 10 nodal failures, 4 in the axillary and 6 in the supraclavicular regions, in 9 patients, at a median of 56.5 and 27 months, respectively. There was no internal mammary node failure. Median follow-up was 72.6 months. The 10-year probability of developing axillary and supraclavicular failure is 13.9 +/- 7.7% and 10.5 +/- 4.1%, respectively. Prognosis was better for patients with axillary and breast recurrence and worse when relapse was in the supraclavicular region. On the basis of our results and data already published in premenopausal patients, we believe that radiotherapy to the supraclavicular region should be considered in patients with four or more positive axillary nodes, after a complete dissection.

This review analyzes PET images in radiotherapy treatment planning for lung cancer patients and discusses the most controversial current issues. Computed tomography images are commonly used to assess location and extension of target volumes and organs at risk in radiotherapy treatment planning. Although PET is more sensitive and specific, contouring on PET images is difficult because tumor margins are indistinct, due to heterogeneous (18)fluorodeoxyglucose uptake distribution and limited spatial resolution. The best target delineation criteria have not yet been established. In non-small-cell lung cancer, PET appears to improve sparing of organs at risk and reduce the risk of toxicity; prescribed doses can be increased. Data are scarce on small-cell lung cancer.

As a component of myeloablative conditioning before allogeneic hematopoietic stem cell transplantation (HSCT), Total Body Irradiation (TBI) is employed in radiotherapy centers all over the world. In recent and coming years, many centers are changing their TBI setup to a conformal isocentric technique, providing superior homogeneity and control of the target prescription dose, and more freedom for individualized organ-at-risk sparing or dose-escalation. Also, more specifically bone-marrow- and/or lymphatics-targeted therapies such as Total Marrow (+ Lymphoid) Irradiation (TMI / TMLI), and Total Lymphoid Irradiation (TLI) are established and prospectively evaluated in several centers. With each center developing their own methods, a new practice heterogeneity is arising, as was the case for decades with conventional TBI. To provide a ground base - and therefore more options for more homogeneous and comparable practice - for centers who are implementing conformal isocentric techniques, a group of early adopters of isocentric conformal TBI and TM(L)I came together to convey issues they encountered during clinical implementation, and form consensus recommendations for delineation and planning targets, based on available literature evaluation and shared experience. These recommendations follow previously published recommendations regarding technical setup of conformal isocentric TBI / TM(L)I techniques.