Brenda Shank

Allogeneic Bone Marrow Transplantation after Hyperfractionated Total-Body Irradiation and Cyclophosphamide in Children with Acute Leukemia

Ninety-seven children with either acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) received HLA-identical bone marrow transplants from sibling donors, after preparation with 1320 cGy of hyperfractionated total-body irradiation and high-dose cyclophosphamide. Kaplan-Meier product-limit estimates (means +/- SE) of disease-free survival at five years among patients with ALL in second remission, third remission, and fourth remission or relapse were 64 +/- 9, 42 +/- 14, and 23 +/- 11 percent, respectively, with probabilities of relapse of 13 +/- 7, 25 +/- 13, and 64 +/- 16 percent. Among patients with AML in first remission, second remission, and third remission or relapse, five-year disease-free survival estimates were 66 +/- 10, 75 +/- 15, and 33 +/- 19 percent, with respective relapse probabilities of 0, 13 +/- 12, and 67 +/- 19 percent. The most frequent cause of death in patients in early remission (ALL in second or third remission or AML in first or second remission) was bacterial sepsis, fungal sepsis, or both, most often in the presence of acute or chronic graft-versus-host disease. Among patients with ALL who received transplants while in second remission, the duration of the initial remission had no effect on the probability of relapse after transplantation. The only pretransplantation factor that significantly affected outcome was the disease status at the time of transplantation; patients in early remission had better disease-free survival. We conclude that transplantation after preparation with hyperfractionated total-body irradiation and cyclophosphamide is an effective mode of therapy in children with refractory forms of acute leukemia.

The patient's perception of her breast following radiation and limited surgery

Seventy-four patients followed from 1 to 8 years post completion of breast-conserving surgery and radiation for early-stage breast cancer were asked to answer a questionnaire exploring their perception and awareness of the treated breast. The questionnaire was divided into several sections, including Daily Activities, Pre-menstrual Changes, Sexual Activities, and a summary Satisfaction Index section; when appropriate, comparisons were sought between the treated and untreated breasts. Preliminary results from this study indicate that 70% of all patients are aware of their treated breast in some way during everyday activities. The Satisfaction Index of this patient group is very high, with 75% rating their cosmetic result, and 81% their functional result 8 or higher on a scale of 0 to 10,10 indicating best or normal.

Can total body irradiation be supplanted by busulfan in cytoreductive regimens for bone marrow transplantation

INTRODUCHON Total body irradiation (TBI) has been one of the primary components of cytoreductive regimens for bone marrow transplantation (BMT) since its early development, usually in combination with cyclophosphamide (CY) f other agents. With modification of irradiation treatment parameters, most importantly the fractionation scheme, TBI regimens have been found to be effective and the morbidity of the entire regimen has been decreased substantially. Investigators have been searching for other effective and potentially less toxic regimens that do not involve TBI. Such chemotherapy-only regimens could have logistic benefits (no transporting of immunosuppressed patients through busy hospital corridors and no scheduling delays for large blocks of treatment time in active departments). The important questions are: (a) Can any chemotherapyonly regimen yield an equivalent or better survival than a TBI-containing regimen? and (b) Can morbidity be reduced by such a regimen? Autologous BMT In this issue, Dusenbery et al. (5) have compared, in a study with only 35 patients, the results of autologous BMT using either BU/CY (busulfan/cyclophosphamide) or CY/ TBI for patients with acute myeloid leukemia (AML) in first or greater remission. Although disease-free survival and relapse rates appear to favor CY/TBI, the differences seen are not statistically significant with such small patient numbers in each arm, and the authors appropriately conclude that CY/TBI provided an “equivalent or better outcome” than BU/CY. In the subgroup of patients with AML in greater than first remission, there was a 42% disease-free survival (DFS) at 2 years for the 12 patients who received CY/TBI compared with only 9% for the 11 patients who received BU/CY (p = 0.06). Clearly, for autologous BMT, more studies with a larger number of patients need to be performed before any definitive conclusions can be made. We have more data available regarding the results of allogeneic BMT and CML for acute leukemias comparing CY/TBI or other TBI-containing cytoreduction regimens with BU/CY. Allogeneic BMT (acute leukemia) A French randomized study (GEGMO) (1) comparing CY/TBI with BU/CY for 101 patients with AML in first remission had a significantly better DFS, overall survival (OS), and relapse rate (RR) in the CY/TBI arm. At 2 years, DFS was 72% for CY/TBI vs. 47% for BU/ CY; OS was 75% and 5 l%, respectively, and RR was 14% and 34%. Another French study (7) in children I 16 years old with AML in first remission (nonrandomized) demonstrated no difference in RR or event-free survival (EFS), when a BU/CY regimen with 200 mg/kg CY was used (as in the Dusenbery study in this journal) compared with CY/TBI (RR = 13% and 10% and EFS = 82% and 80%, respectively). Busulfan/CY with only 120 mg/kg CY was significantly inferior, with RR of 54% and EFS of only 46%. A retrospective study of 123 patients from the Japanese Bone Marrow Transplant Registry (6) demonstrated a significantly better OS (77%) and RR (16%) at 2 years for the 8 1 patients who had a TBI-containing regimen (mostly CY/TBI) compared with the 42 patients who had chemotherapy-only regimens (mostly BU/CY), who had an OS of 5 1% and RR of 37%. Interstitial pneumonitis was not significantly different between the two regimens. Allogeneic BMT (chronic myelogenous leukemia)

Bone marrow transplantation in two multiply transfused patients with thalassaemia major.

Bone marrow transplantation has generally been unsuccessful when applied to patients with thalassaemia major over the age of 6 years. We report here two successful transplants for this disorder in a 7‐year‐old boy and an 11‐year‐old girl following a pre‐transplant cytoreductive/immunosuppressive regimen of total body irradiation and cyclophosphamide. Complete durable engraftment of donor haematopoietic and lymphoid populations was documented through several approaches, including cytogenetic analysis, haemoglobin electrophoresis, globin chain synthetic ratios, red cell typing and DNA restriction enzyme analysis. Both patients are surviving in good health, 28 and 9 months from transplantation. The successful outcome in these patients demonstrates the feasibility of marrow transplantation for the treatment of thalassaemia in multiply transfused and, presumably, highly sensitized patients.