Data on 405 patients with chronic myelogenous leukemia who received bone marrow transplants in chronic phase were analyzed for factors predictive of outcome. The 4-year actuarial probability of relapse was 19% (95% confidence interval [CI], 12% to 28%) and of survival, 55%. In multivariate analyses the probability of relapse was higher for recipients of T-cell-depleted bone marrow compared with recipients of non-T-cell-depleted bone marrow (relative risk, 5.4; P less than 0.0001) and for patients who did not develop chronic graft-versus-host disease (95% CI, 50% to 60%) with patients who did (relative risk, 3.1; P less than 0.01). The probability of survival was lower for patients who developed moderate to severe acute graft-versus-host disease than for patients with no or mild acute graft-versus-host disease (relative risk, 3.7; P less than 0.0001), and in patients aged 20 or older than in younger patients (relative risk, 2.6; P less than 0.0002). Duration of disease before transplant was not associated with outcome. Bone marrow transplantation done in the chronic phase of chronic myelogenous leukemia offers some patients prolonged leukemia-free survival. The T-cell-depleted grafts are associated with an increased probability of relapse.

Acute graft-versus-host disease (GvHD) is an important complication of bone marrow transplantation in humans. Risk factors are imprecisely defined and controversial. We analysed data from 2036 recipients of HLA-identical sibling transplants for leukaemia or aplastic anaemia to identify risk factors for GvHD. Analyses indicate that grading of GvHD can be reproducibly divided into absent or mild versus moderate to severe; 2-year actuarial probability was 54% (95% confidence interval 52-56%) for absent or mild and 46% (44-48%) for moderate to severe. Factors predictive of development of moderate to severe GvHD include donor/recipient sex-match (female----male greater than others, relative risk 2.0, P less than 0.001). This risk was markedly increased if female donors for male recipients were previously pregnant or transfused (relative risk 2.9, P less than 0.0001). Older patients were at increased risk of GvHD (relative risk 1.6, P less than 0.001), but the age gradient was modest, even the youngest patients had a substantial risk of GvHD and, if parous or transfused female----male transplants were excluded, age was not a significant risk factor. Cyclosporine or methotrexate were equally effective at preventing GvHD and were superior to no prophylaxis (relative risk 2.3, P less than 0.01). These data should be useful in estimating the risk of acute GvHD in an individual patient and in designing clinical trials to investigate methods to modify or prevent GvHD.

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Summary:Autologous haemopoietic stem cell transplantation (HSCT) represents a potential therapy for severe rheumatoid arthritis (RA). As a prelude to clinical trails, the safety and efficacy of haemopoietic stem cell (HSC) mobilisation required investigation as colony-stimulating factors (CSFs) have been reported to flare RA. A double-blind, randomised placebo-controlled dose escalation study was performed. Two cohorts of eight patients fulfilling strict eligibility criteria for severe active RA (age median 40 years, range 24-60 years; median disease duration 10.5 years, range 2-18 years) received filgrastim (r-Hu-methionyl granulocyte(G)-CSF) at 5 and 10 g/kg/day, randomised in a 5:3 ratio with placebo. Patients were unblinded on the fifth day of treatment and those randomised to filgrastim underwent cell harvesting (leukapheresis) daily until 2 ؋ 10 6 /kg CD34 ؉ cells (haemopoietic stem and progenitor cells) were obtained. Patients were assessed by clinical and laboratory parameters before, during and after filgrastim administration. RA flare was defined as an increase of 30% or more in two of the following parameters: tender joint count, swollen joint count or pain score. Efficacy was assessed by quantitation of CD34 ؉ cells and CFU-GM. One patient in the 5 g/kg/day group and two patients in the 10 g/kg/day group fulfilled criteria for RA flare, although this did not preclude successful stem cell collection. Median changes in swollen and tender joint counts were not supportive of filgrastim consistently causing exacerbation of disease, but administration of filgrastim at 10 g/kg/day was associated with rises in median C-reactive protein and median rheumatoid factor compared with placebo. Other adverse events were well recognised for filgrastim and included bone pain (80%) and increases in alkaline phosphatase (four-fold) and lactate dehydrogenase (two-fold). With respect to efficacy, filgrastim at 10 g/kg/day was more efficient with all patients (n = 5) achieving target CD34 ؉ cell counts with a single leuCorrespondence: Dr JA Snowden, Department of Haematology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK Received 2 May 1998; accepted 21 July 1998 kapheresis (median = 2.8, range = 2.3-4.8 ؋ 10 6 /kg, median CFU-GM = 22.1, range = 4.2-102.9 ؋ 10 4 /kg), whereas 1-3 leukaphereses were necessary to achieve the target yield using 5 g/kg/day. We conclude that filgrastim may be administered to patients with severe active RA for effective stem cell mobilisation. Flare of RA occurs in a minority of patients and is more likely with 10 than 5 g/kg/day. However, on balance, 10 g/kg/day remains the dose of choice in view of more efficient CD34 ؉ cell mobilisation.