No abstract

Summary. The number of long-term survivors after allogeneic bone marrow transplantation (BMT) has been increasing over the past years, and quality of life (QOL) has become an important end-point. We studied 244 patients undergoing an allogeneic BMT to identify factors and events influencing psychosocial outcome. Patients enrolled received the Psychosocial Adjustment to Illness Scale (PAIS) questionnaire assessing psychological and social adjustment to chronic illness or its sequelae. Eightytwo per cent of patients had a haematological disease. The median age was 28 years at BMT, and the median follow-up was 61 months. The median overall PAIS score for all patients was 56 (range 22±76): 25% (n 61) of patients were considered to have a good QOL (# 25 percentile score); 44% (n 108) of patients had an intermediate QOL (26± 75 percentile score) and 31% (n 75) had a poor QOL (. 75 percentile score). Factors associated with a poor QOL in multivariate analysis were: patients' age at BMT (. 25 years, P , 0´01); presence of long-term sequelae (P , 0´01); chronic graft-versus-host disease (GVHD) (P , 0´05); and a short interval from BMT (, 5 years; P , 0´05). The QOL improved with time: 12% of patients reported a good QOL within 5 years compared with 38% after this time point and, conversely, 38% reported a poor QOL within 5 years compared with 24% after this time point (P , 0´0001). Older patients had significantly poorer QOL compared with younger patients (# 25 years; P 0´01). Females had significantly poorer scores when compared with males in the sexual (P , 0´0001) and psychological domains (P 0´001). The data suggest that (i) one-third of patients undergoing allogeneic BMT report a poor QOL; (ii) factors associated with poor QOL are older age, presence of long-term sequelae, chronic GVHD and short follow-up; (iii) QOL is superior in long-term survivors; and (iv) BMT affects different aspects of life in males and females. A longitudinal study is ongoing to prove the effect of time on quality of life.

Platelet recovery after allogeneic haemopoietic stem cell transplant (HSCT) and predictive factors were analysed in 342 patients with haematological malignancies. All patients were prepared with cyclophosphamide plus total body irradiation, and received an unmanipulated HSCT from an HLA‐identical sibling (n = 270), a matched unrelated donor (n = 67) or an identical twin (n = 5). The source of stem cells was peripheral blood (n = 15) or bone marrow (n = 327). Graft‐vs.‐host disease (GvHD) prophylaxis consisted of cyclosporin A with or without methotrexate. The proportion of patients with < 50 × 109/l platelets on d +50, d +100, d +200 and d +365 after HSCT was 26%, 27%, 14% and 11% respectively. Thrombocytopenia was independent of the degree of complete donor chimaerism. Four variables were predictive of platelet recovery: donor type, acute GvHD, cytomegalovirus (CMV) infection and number of cells infused at transplant. Recipients of an unrelated graft had lower platelet counts (49 × 109/l) on d +50 than identical sibling grafts (108 × 109/l) (P < 0·001) and twin grafts (149 × 109/l) (P < 0·001). Patients with GvHD grades 0, I, II, III and IV had significantly different platelet counts on d +50 (153 × 109/l, 102 × 109/l, 85 × 109/l, 32 × 109/l and 22 × 109/l; P < 0·001) and thereafter. Thrombocytopenia was more frequent in patients with high‐level CMV antigenaemia (> four positive cells/2 × 105) (P < 0·0001) and in patients who received a low cell dose at transplant (≤ 4·1 × 108/kg) (P = 0·009). Platelet counts predicted transplant‐related mortality (TRM) and were higher at all time intervals in patients surviving the transplant. Patients with grade II GvHD and > 50 × 109/l platelets had a lower TRM than patients with grade II GvHD and ≤ 50 × 109/l platelets (14% vs. 40%, P < 0·0001). In conclusion, (i) a significant proportion of allogeneic HSCT recipients are thrombocytopenic long‐term, irrespective of complete donor chimaerism, (ii) thrombocytopenia identifies patients at greater risk of lethal complications, and (iii) platelet recovery is influenced by GvHD, donor type, CMV infections and cell dose, not by stem cell source or other patient–disease‐related variables.

We have studied the impact of cell dose on short-and long-term graft function and outcome in 905 patients undergoing an unmanipulated allogeneic bone marrow transplantation (BMT) from an HLAidentical sibling (n ‫؍‬ 735), a one-antigen mismatched related donor (n ‫؍‬ 35), or a matched unrelated donor (n ‫؍‬ 135). Median number of nucleated cells infused was 3.4 ؋ 10 8 /kg (25th percentile 2.4 ؋ 10 8 /kg, 75th percentile 5 ؋ 10 8 /kg). Patients were stratified according to cells infused in 3 groups: < 2.4 ؋ 10 8 /kg (n ‫؍‬ 247; low dose); >2.4 ؋ 10 8 /kg and < 5 ؋ 10 8 /kg (n ‫؍‬ 452; intermediate dose); and >5 ؋ 10 8 /kg (n ‫؍‬ 206; high dose). Patients receiving high cell dose had significantly higher platelet counts on days ؉20, ؉50, ؉100, ؉180, and ؉365 after BMT (P < .01) and higher white blood cell counts on days ؉50, ؉100, and ؉180 after BMT (P < .01) as compared with other patients. The actuarial 5-year transplantrelated mortality (TRM) was 41% versus 36% versus 28% (P ‫؍‬ .01); overall survival was 45% versus 51% versus 56% (P ‫؍‬ .0008); and disease-free survival was 41% versus 42% versus 48%, respectively, (P ‫؍‬ .04) in patients receiving low, intermediate, or high cell dose. The cell dose effect was more pronounced in patients older than 30 years of age, with advanced disease, with chronic myeloid leukemia, and with alternative donors. In multivariate Cox analysis on TRM, cell dose was a significant predictor (P ‫؍‬ .002; relative risk 0.6) together with donor type (P ‫؍‬ .0001), year of transplantation (P ‫؍‬ .0001), conditioning regimen (P ‫؍‬ .02), and recipient age (P ‫؍‬ .02). In conclusion, transplantation of high marrow cell dose is associated with reduced transplant mortality and improved survival and results in improved graft function both short and long term. (Blood. 2002;100:3930-3934)

Summary:This trial was designed to compare foscarnet with ganciclovir as pre-emptive therapy for CMV infection in patients undergoing allogeneic hemopoietic stem cell transplant (HSCT). Thirty-nine patients were randomized to receive foscarnet 90 mg/kg every 12 h (n = 20) or ganciclovir 5 mg/kg every 12 h (n = 19) for 15 days at the time of development of CMVAg-emia. Primary-end points of the study were (1) outcome of CMVAg-emia; (2) progression to CMV disease; and (3) side-effects of treatment. The secondary end-point was transplant-related mortality (TRM). The two groups were comparable for diagnosis, status of disease, donor type, acute graft-versus-host (aGVHD) prophylaxis, interval between HSCT and CMVAg-emia and number of CMVAg positive cells; the donor and recipient age were borderline older in the foscarnet group. Increments of serum creatinine in the foscarnet group, and cytopenia in the ganciclovir group were controlled by reducing the administered dose: in the first 15 days of therapy 9/20 foscarnet and 10/19 ganciclovir patients had a dose reduction greater than 20% (P = 0.43). Clearance of CMVAg-emia was faster in the foscarnet group although with borderline statistical significance. Failures of treatment occurred in 3/20 patients in foscarnet group vs 8/19 patients in ganciclovir group (P = 0.06): causes of failure were the need for combination therapy to control antigenemia (1/20 vs 5/19), and reactivation during treatment for 2 vs 3 patients, respectively. CMV disease was diagnosed in 1 vs 2 patients (P = 0.5) who subsequently died. The actuarial 1-year TRM was 25 vs 12%, respectively (P = 0.3). This study suggests that foscarnet and ganciclovir are both effective for pre-emptive therapy of CMVAg-emia, although the number of failures would seem to be slightly higher in the ganciclovir patients. Side-effects are seen in both groups and can be managed with appropriate dose reduction.