The CD34 antigen is present on 1-4% of human marrow

A randomized trial of 12.0 Gy versus 15.75 Gy of total body irradiation (TBI) was performed in patients with acute myeloid leukemia undergoing allogeneic marrow transplantation while in first complete remission. All patients received 120 mg/kg cyclophosphamide followed by TBI and marrow from HLA-identical siblings. Cyclosporine and methotrexate were used for prophylaxis against acute graft-versus-host disease (GVHD). Thirty-four patients received 2.0-Gy fractions of irradiation daily for 6 days and 37 received 2.25-Gy fractions daily for 7 days. The 3-year actuarial probabilities for relapse-free survival were 0.58 for the patients who received 12.0 Gy and 0.59 for those who received 15.75 Gy. The 3-year probabilities of relapse were 0.35 for the 12.0 Gy group and 0.12 for the 15.75 Gy group (P = .06). The 3-year probabilities of transplant-related mortality were 0.12 and 0.32, respectively (P = .04). The probability of moderate to severe acute GVHD was 0.21 for the 12.0 Gy group and 0.48 for the 15.75 Gy group (P = .02). Patients exposed to the higher irradiation dose received less immunoprophylaxis against, and had a higher incidence of, acute GVHD. The increased dose of TBI significantly reduced the probability of relapse but did not improve survival because of increased mortality from causes other than relapse.

Abstract. Peripheral blood stem cells (PBSC) are increasingly utilized in lieu of marrow for hematopoietic support due to the ease of collection and the rapid kinetics of recovery relative to bone marrow (BM). Neutrophil and platelet recovery times after PBSC transplantation average less than 8-12 days after infusion in contrast to the usual two to four weeks experienced after BM transplantation. This has simplified autologous transplantation and made it safer because patients require fewer days of antibiotic and blood component support and are discharged earlier from the hospital. The administration of hematopoietic growth factors during recovery from high-dose chemotherapy increases the number of circulating hematopoietic progenitor cells to levels as much as 1,000-fold greater than levels normally found in blood and 10-50 times greater than with chemotherapy alone. More recently, it has been shown that adequate numbers of PBSC can be collected using growth factors alone without prior chemotherapy.Although not yet universally accepted, the CD34 + cell content of PBSC appears to be the single most powerful predictor of recovery kinetics in patients receiving myeloablative therapy and PBSC infusion. Infusion of >5 × 10 6 CD34 + cells/kg is associated with a rapid engraftment of neutrophils and platelets, although successful engraftment has also been reported with the infusion of 2.5-5 × 10 6 CD34 + cells/kg. By measuring the CD34 or colony forming units-granulocyte-macrophage (CFU-GM) content of PBSC collections, mobilization chemotherapy and cytokine regimens, age, marrow disease, prior radiation and prior chemotherapy treatment have been found to be important factors influencing the numbers of stem cells collected. The current challenge for clinical investigators is to improve methods of identifying patients who will fail to mobilize sufficient numbers of PBSC prior to collection and to utilize new strategies for stem cell mobilization. The relative ease of collection and the rapid engraftment after myeloablative therapy suggest that PBSC will likely supplant marrow for both allogeneic and autologous transplantation in the next five years.

The purpose of this study was to determine the effectiveness of second mobilization strategies in patients who yielded < 2.5 x 10(6) CD34+ PBSC/kg after initial mobilization. Repeat mobilization attempts were made with chemotherapy and G-CSF (n = 61) or G-CSF alone (n = 58) in patients who failed initial mobilization with chemotherapy and G-CSF (n = 92) or G-CSF alone (n = 27). A median of 0.27 x 10(6) CD34+ cells/kg per apheresis was collected after the second mobilization, compared with 0.16 with initial harvests (p = 0.0001). Forty-eight percent achieved a target CD34+ cell dose > or = 2.5 x 10(6)/kg when harvests from the first and second mobilizations were combined. Fifteen of 17 patients (88%) with > or = 1.5 x 10(6) CD34+ cells/kg harvested after first mobilization had > or = 2.5 x 10(6) CD34+ cells/kg collected when first and second harvests were combined, as compared with 42 of 102 (41%) achieving < 1.5 x 10(6) CD34+ cells/kg with first PBSC harvests (p = 0.0001). Second mobilizations with chemotherapy and G-CSF or G-CSF alone resulted in similar CD34+ cell yields. Toxicities of second mobilizations were comparable with those of first mobilizations. Seventy-nine patients (66%) received high-dose chemotherapy with PBSC support, with recovery of neutrophils and platelets in a median of 11 and 15 days, respectively. Transplant-related mortality was 4%, and event-free survival at 2 years was 0.34. It was concluded that second mobilization attempts in patients who fail to achieve > or = 2.5 x 10(6) CD34+ cells/kg on initial mobilization were successful in 48% of patients. G-CSF alone was as effective as chemotherapy plus G-CSF in mobilizing CD34+ cells and was associated with less morbidity.

It was concluded that filgrastim alone or sequential sargramostim and filgrastim were superior to sargramostim alone for the mobilization of CD34(+) cells and reduction of toxicities after MC.

A prospective randomized study was conducted comparing two conditioning regimens for the treatment of patients with chronic myeloid leukemia in chronic phase by marrow transplantation from HLA identical siblings. Sixty-nine patients received 60 mg/kg of cyclophosphamide on each of 2 successive days followed by 6 fractions of total body irradiation each of 2.0 Gy (CY-TBI), and 73 patients received 16 mg/ kg of busulfan delivered over 4 days followed by 60 mg/kg CY on each of 2 successive days (BU-CY). There was no significant difference between the CY-TB1 and the BU-CY groups in the 3-year probabilities of survival (0.80 for both), relapse (0.13 for both), or event-free survival (CY-TBI, 0.68; BU-CY, 0.71) or in speed of engraftment or incidence MARKED IMPROVEMENT in the results of marrow transplantation for treatment of chronic myeloid leukemia (CML) in chronic phase (CP) has been reported over the past 10 years."4 A major factor in producing this improvement was the introduction of a regimen using both methotrexate (MTX) and cyclosporine (CSP) for the prevention of acute graft-versus-host disease (GVHD).' Most regimens used for transplant conditioning during this period included total body irradiation (TBI), and the most widely used such regimen was cyclophosphamide (CY) administered at a dose of 60 m g k g on each of 2 successive days, followed by 2.0 Gy of TB1 administered on each of 6 successive days (CY-TBI).' In 1987, Tutschka reported the use of a conditioning regimen consisting of busulfan (BU; 16 mg/kg administered over 4 days), followed by 60 m g k g CY on each of 2 successive days (BU-CY).' This regimen had low toxicity, was effective in facilitating allogeneic engraftment, and appeared to be particularly effective in the treatment of patients with myeloid malignancy. Although this regimen has been used increasingly in the treatment of patients with CML in CP,' no formal comparison with the CY-TB1 regimen has been reported. In 1988, we began a randomized study comparing these regimens in patients receiving marrow transplants from HLA-identical related donors for the A From The Fred Hutchinson Cancer Reseurch Center and the Vet-The pUblicUtiCJn costs of this article were defruved in part by page charge payment. This urticle must therefore he herebv marked "advertisement" in accorhnce with 18 U.S.C. section 1734 solel)) to indicate this juct. S e d r , WA, 98104-2092. 0 1994 by The Americun Society qf Hemutoiogy. 0006-497//94/8406-0022$3.00/0 2036 of venocclusive disease of the liver. The 4-year probabilities of survival and event-free survival for patients transplanted within 1 year of diagnosis were 0.86 and 0.72, respectively, for each group. Significantly more patients in the CY-TB1 group experienced major creatinine elevations. There was significantly more acute graft-versus-host disease in the CY-TB1 group. Fever days, positive blood cultures, hospitalizations, and inpatient hospital days were significantly more common in the CY-TB1 group than in the BU-CY group. In conclusion, the BU-CY regimen...

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