Physical activity and blood pressure in 10,000 Mediterranean adults: The EPIC-Florence cohort.

BACKGROUND AND AIMS: The relevant role of physical activity (PA) in cardiovascular risk prevention is widely agreed. We aimed to evaluate, in a large Mediterranean population, the influence of PA on systolic (SBP) and diastolic blood pressure (DBP), taking into account individual characteristics and lifestyle habits. METHODS AND RESULTS: In the Florence section of the European Prospective Investigation into Cancer and Nutrition 10,163 individuals, 35-64 years, without a previous diagnosis of hypertension were recruited. Information on occupational and leisure-time PA and blood pressure were collected at recruitment, together with data on lifestyle, dietary habits and anthropometry. Multivariate regression models were applied to evaluate the effect of total, occupational and leisure-time PA on SBP and DBP. Mean values of SBP and DBP in the study subjects were 124.4 (SD 15.6) and 79.7 mmHg (SD 9.4), respectively. Overall, a total PA index and an index including cycling, fitness and occupational PA (Cambridge index) were inversely associated with DBP (beta -0.87, p-value 0.02 actives vs inactives, p for trend 0.02 and beta -0.84, p value 0.003 actives vs inactives, p for trend 0.002, respectively), while SBP was associated only with the latter index (beta -1.14, p-value 0.01 actives vs inactives, p for trend 0.006). An inverse association emerged between manual/heavy manual occupation and DBP (p 0.02, ref sedentary/standing occupation) and between increasing cycling activity and SBP (p for trend 0.04). CONCLUSIONS: In this large cohort of Mediterranean adults without a diagnosis of hypertension we confirm the role of overall PA in modulating SBP and DBP values. Cycling and manual occupations were associated with lower DBP values.

Inflammatory marker changes in a 24-month dietary and physical activity randomised intervention trial in postmenopausal women.

Chronic low-grade inflammation plays a role in the pathogenesis of several chronic diseases including cancer. Physical activity (PA) and diet have been supposed to modulate inflammatory markers. We evaluated the effects of a 24-month dietary and/or PA intervention on plasma levels of pro-inflammatory cytokines, a secondary analysis in the DAMA factorial trial. The 234 study participants (healthy postmenopausal women with high breast density, 50-69 years, non smokers, no hormone therapy) were randomised to four arms: (1) isocaloric dietary intervention mainly based on plant-foods; (2) moderate-intensity PA intervention with at least 1 h/week of supervised strenuous activity; (3) both interventions; (4) general recommendations on healthy dietary and PA patterns. Interleukins (IL)-1α, -1ß, -6, tumor necrosis factor-α and C-reactive protein were measured at baseline and at the end of the intervention. Intention-to-treat-analyses were carried out using Tobit regression. Although all cytokines tended to increase over time, after 24 months women in the PA intervention (arms 2 + 3) showed lower levels of IL-1α (exp(ß) = 0.66; p = 0.04) and IL-6 (exp(ß) = 0.70; p = 0.01) in comparison with women in the control group (arms 1 + 4). No effects of the dietary intervention emerged. In healthy postmenopausal women with high breast density a moderate-intensity PA appears to slow the age-related increase of pro-inflammatory cytokines.

Improved outcome in young adults with de novo acute myeloid leukemia in first remission, undergoing an allogeneic bone marrow transplant.

We assessed the outcome of 170 patients with AML in first complete remission, aged 1-47 years (median 29), who had undergone an allogeneic BMT before or after 1990 (n=80 and n=90, respectively); all patients were prepared with cyclophosphamide and TBI; the median follow-up for surviving patients was 13 years. The donor was an HLA-identical sibling in 164 patients. Transplant-related mortality (TRM) was 30% before and 7% after 1990 (P<0.001); relapse-related death (RRD) was 26 and 11% (P=0.002); and actuarial 10-year survival was 42 and 79% (P<0.00001). Patients transplanted after 1990 were older, had a shorter interval diagnosis-BMT, had less FAB-M3 cases, received a higher dose of TBI, a higher marrow cell dose and combined (cyclosporine+methotrexate) GVHD prophylaxis. Patients relapsing after transplant had an actuarial survival of 0 vs 31% if grafted before or after 1990 (P=0.01), and their median follow-up exceeds 10 years. In conclusion, the overall survival of first remission AML undergoing an allogeneic BMT has almost doubled in the past two decades, despite older age and fewer M3 cases. Improvement has come not only from changes in transplant procedures, but also from effective rescue of patients relapsing after transplant.

Allogeneic hemopoietic stem cell transplants for patients with relapsed acute leukemia: long-term outcome.

We assessed the long-term outcome of patients with relapsed acute myeloid (n=86) or acute lymphoid leukemia (n=66), undergoing an allogeneic hemopoietic stem cell transplantation in our unit. The median blast count in the marrow was 30%. Conditioning regimen included total body irradiation (TBI) (10-12 Gy) in 115 patients. The donor was a matched donor (n=132) or a family mismatched donor (n=20). Twenty-two patients (15%) survive disease free, with a median follow-up of 14 years: 18 are off medications. The cumulative incidence of transplant related mortality is 40% and the cumulative incidence of relapse related death (RRD) is 45%. In multivariate analysis of survival, favorable predictors were chronic graft-versus-host disease (GvHD) (P=0.0003), donor other than family mismatched (P=0.02), donor age less than 34 years (P=0.02) and blast count less than 30% (P=0.07). Patients with all four favorable predictors had a 54% survival. In multivariate analysis of relapse, protective variables were the use of TBI (P=0.005) and cGvHD (P=0.01). This study confirms that a fraction of relapsed leukemias is cured with an allogeneic transplant: selection of patients with a blast count <30%, identification of young, human leukocyte antigen-matched donors and the use of total body radiation may significantly improve the outcome.

Catastrophic relapse of Evans syndrome five years after allogeneic BMT notwithstanding full donor chimerism. Terminal hemolytic-uremic syndrome.

A patient with severe Evans syndrome received an allo-BMT from his HLA-identical sister on November, 2000. Full marrow and blood donor chimerism were achieved only after 5 donor lymphocyte infusions (DLI), and coincided with complete clinical remission and disappearence of auto-antibodies. Five years later, hemolytic anemia recurred with rapid increase of serum bilirubin to over 50 mg%: he responded to combined therapy, but died on day +17 from admission of an acute hemolytic uremic syndrome (HUS). All circulating blood cells, including erythrocytes, were 100% donor. Ex vivo cultured and expanded T and B cells from the peripheral blood were also 100% donor. The supernatants from B cell cultures, containing either IgM or IgG, did not react with a panel of erythrocytes. Thus in this typical autoimmune disease with a predominant B cell pathogenesis the donor immune system resulted "innocent of autoimmunity". The persistence of long-lived recipient autoreactive plasma-cell lines in survival niches, still producing autoantibodies, may be hypothesized for this and similar cases. The postulated graft-versus-autoimmunity (GVA) effect was apparently not sufficient to eradicate autoimmunity in this patient.

Nine years' experience with ABMT in 128 patients with Hodgkin's disease: an Italian study group report.

One-hundred, twenty-eight patients with Hodgkin's disease in remission or who had failed a mechlorethamine, vincristine, procarbazine and prednisone (MOPP), a doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and/or lomustine, etoposide and prednimustine (CEP) regimens have been treated with a high-dose therapy (HDT) containing cyclophosphamide, etoposide, carmustine (CVB) and autologous bone marrow transplantation (ABMT). Forty patients were treated while they were in resistant or progressive disease states using alternating MOPP/ABVD protocol; 15 patients received ABMT in first relapse; 51 patients had a complete remission (CR) with first-line therapy but later relapsed and then received conventional salvage therapy; 16 achieved no response or progression ("resistant relapse" patients) and 35 responded partially or completely ("sensitive-relapse" patients). The other 22 patients received ABMT in remission. Following HDT, 56 patients (52.8%) achieved CR and 23 patients (21.6%) achieved a partial remission for an overall response rate of 74.4%. Sixteen patients failed to respond and died in progressive disease 1 to 10 months (median 6 months) after ABMT. High-dose therapy produced severe toxicity including vomiting (100%), mucositis (75%) and liver enzymes and alkaline phosphatase elevations (51%). There were 10 treatment-related deaths. A multivariate analysis identified poor performance status and resistant-relapse patients as very important adverse risk factors for survival immediately after ABMT. These results, while validating this procedure for inducing remissions in advanced highly-treated patients, at the same time confirm the need of employing this approach in first relapse or in second complete remission after standard therapy and before ABMT or, in first complete remission in very high risk Hodgkin's disease patients. Our experience in 15 very poor prognosis Hodgkin's disease patients transplanted in first CR demonstrated to be much significant.

Allogeneic bone marrow or peripheral blood cell transplants in adults with hematologic malignancies: a single-center experience.

This is a retrospective study of 97 patients who received either allogeneic bone marrow transplant (BMT) (n=52) or peripheral blood cell transplant (PBCT) (n=45) at our institution from human leukocyte antigen (HLA)-identical sibling donors between January 1994 and January 1997. The two groups were comparable with respect to diagnosis, age, sex, interval from diagnosis, and disease phase. They were prepared with cyclophosphamide (CY) and fractionated total-body irradiation (TBI) (n=51) or CY and thiotepa (n=46). Graft-vs.-host disease (GVHD) prophylaxis consisted of cyclosporin A and methotrexate. Patients who received PBCT exhibited faster neutrophil engraftment (day 14 vs. day 16, p = 0.002) than those in the BMT group, as well as higher platelet counts on day 20 (32x10(9)/kg vs. 21x10(9)/kg, p = 0.001), but graft function as assessed by platelet counts on days 50, 100, and thereafter was comparable. The number of days spent in the hospital, days on intravenous antibiotics, and days of fever were lower in the PBCT group, but not significantly. Acute GVHD, chronic GVHD, and cytomegalovirus infections were comparable between the two groups. The overall actuarial 3-year transplant-related mortality (TRM) rate for BMT vs. PBCT patients was 20 vs. 33% (p = 0.1), the survival rate was 53 vs. 48% (p = 0.3), and the relapse rate was 42 vs. 43% (p = 0.8). For patients in first complete remission, these figures were TRM 12 vs. 22% (p = 0.2), survival rate 75 vs. 70% (p = 0.4) and relapse rate 31 vs. 9% (p = 0.4), respectively, for the BMT and PBCT groups. These data suggest that the short-term outcome of allogeneic PBCT is not significantly different from that of allogeneic BMT in patients with hematologic malignancies. Long-term results are not available at present.

ABO compatibility and acute graft-versus-host disease following allogeneic bone marrow transplantation.

If ABO antigens/antibodies play any role in the pathogenesis of acute graft-versus-host disease (GVHD), one would expect the highest incidence of GVHD in recipients of minor ABO-mismatched grafts, followed by ABO-matched grafts, and the lowest incidence in major ABO-mismatched transplants. To test this hypothesis 174 patients receiving an HLA-identical allogeneic bone marrow transplant (BMT) for aplastic anemia (n = 32) or leukemia (n = 142) were analyzed for factors associated with acute GVHD. Variables analyzed included diagnosis, sex, age, blood group of donor and recipient, ABO compatibility, Rhesus compatibility, sex compatibility, number of bone marrow cells given at BMT, year of transplant, day of engraftment, and GVHD prophylaxis. We first carried out an exploratory contingency table analysis: minor ABO incompatibility was associated with a significantly higher risk of severe acute GVHD when compared with ABO-matched and major-ABO mismatched pairs (P = 0.003): 14/9, 57/67, and 5/22 patients developed, respectively, 0-I/II-IV acute GVHD in ABO major-mismatched, matched, and minor-mismatched pairs. Donors of group 0, (P = 0.06), older recipient's age (P = 0.08), fast engraftment (P = 0.03), and older donor's age (0.08) were also associated with a higher risk of GVHD. Recipient's ABO group, diagnosis, year of transplant, Rhesus group of donor or recipient, Rhesus compatibility, sex of donor or recipient, sex compatibility, and type of GVHD prophylaxis were not predictive of GVHD. A Cox multifactorial proportional hazards analysis confirmed that ABO matching was the single most significant factor associated with GVHD (P = 0.006). The cumulative incidence of GVHD grade II+ was 39%, 54%, and 82% for ABO major-mismatched, matched, and minor-mismatched pairs (P = 0.01). This study suggests that ABO antigens may play a role in the development of acute GVHD.

Combined foscarnet-ganciclovir treatment for cytomegalovirus infections after allogeneic hemopoietic stem cell transplantation.

In a previous study, we showed that patients undergoing allogeneic hemopoietic stem cell transplantation (HSCT) who had cytomegalovirus (CMV) antigenemia with more than 4 CMV antigen-positive cells/200,000 have a high transplant-related mortality (TRM) rate, despite treatment with ganciclovir or foscarnet. In an attempt to reduce TRM, 32 allogeneic HSCT recipients, between the ages of 16 and 55 years (median, 35 years), with CMV antigenemia (> or = 5 positive cells) developing at a median interval from HSCT of 49 days, were given combination treatment with foscarnet and ganciclovir for 15 days. The prescribed dose was 180 mg/kg/day of foscarnet and 10 mg/kg/day of ganciclovir: the median administered dose in the first 15 days, after adjusting for creatinine levels and peripheral blood counts, was 64% for foscarnet and 53% for ganciclovir. Maintenance was given with foscarnet and ganciclovir on alternate days for an additional 2 weeks. Thirty-one of 32 patients were on cyclosporine, 30 were on systemic antibiotics, and 9 were on intravenous amphotericin. Median laboratory values on days 1 and 15 of treatment were 1.0 and 1.1 mg/100 ml creatinine, 5.7 x 10(9)/L, and 4.1 x 10(9)/L white blood cells, and 78 x lO(9)/L and 72 x 10(9)/L platelets. All patients cleared CMV antigenemia by day +15, although CMV antigenemia recurred in 5 patients on maintenance therapy and in 14 patients off maintenance therapy: the dose of foscarnet (but not ganciclovir) received in the first 15 days was significantly lower in patients in whom antigenemia recurred within 30 days (P=0.0002). Six patients died, one with interstitial pneumonia, one with multiorgan failure, and four with infections. Twenty-six patients survived 119-1051 days after transplant. The actuarial TRM rate at 1 year is 23%. Eighteen patients who had received unmanipulated bone marrow transplants from HLA-identical siblings were compared with 15 matched controls who had been treated with a single drug (either foscarnet or ganciclovir) for CMV antigenemia (> or = 5 cells): the actuarial 1 year TRM rate was 13% for patients receiving combined treatment, compared with 47% for controls receiving a single drug (P=0.02). This study shows that combined foscarnet-ganciclovir is one therapeutic option for allogeneic HSCT recipients who develop CMV antigenemia with a high number of CMV antigen-positive cells. Treatment can be given together with cyclosporine and antibiotics with appropriate dose reductions. It produces prompt clearing of CMV infection, and may reduce TRM rates in comparison to single-agent therapy.

Failure of autologous stem cell transplantation in refractory thrombocytopenic purpura.

A 44-year-old man with splenectomised refractory autoimmune thrombocytopenic purpura (AITP) of 10 years' duration underwent an autologous, T cell-depleted marrow transplant following conditioning with thiotepa and CY. There was no response to the transplant procedure. This is the fourth case in the literature to show failure following autologous stem cell transplantation, although complete, steroid-independent remissions were obtained in the first two patients for over 1 year.

Hepatitis B virus (HBV) infection and liver disease after allogeneic bone marrow transplantation: a report of 30 cases.

Among 145 consecutive patients undergoing bone marrow transplantation (BMT) for leukemia or aplastic anemia. 30 (21%) were found positive for hepatitis B surface antigen (HBsAg) in serum either before or after BMT. Their serologic profile and clinical outcome are described. Nine out of 30 patients were HBsAg positive before BMT: four were chronic carriers and five were found HBsAg+ at transplant. Three of the former and one of the five latter patients remained persistently HBsAg+ after transplant with signs of liver disease; none developed liver failure, indicating that HBsAg positivity is not an absolute contra-indication to BMT. Among the remaining 21 patients. HBsAg was detected early (n = 12) or late (n = 9) after transplant. All 21 cleared the antigen during follow-up and liver disease was either mild and asymptomatic (nine cases) or clinically overt (12 cases), but none had life-threatening liver disease. Several HBV-infected patients were constantly seronegative for antibody to HBcAg even in the presence of active HBV replication. These results show that the serologic pattern of HBV markers in BMT patients is unpredictable. HBV infection was rarely associated with severe hepatitis and HBsAg carriage.

Autologous bone marrow transplantation as adjuvant treatment for high-risk Hodgkin's disease in first complete remission after MOPP/ABVD protocol.

Fifteen patients with very poor prognosis Hodgkin's disease in remission after MOPP/ABVD regimen, were treated with high-dose chemotherapy (HDC) and autologous marrow transplantation (ABMT) immediately after achieving complete remission (CR). Thirteen patients (86.6%) remain alive in unmaintained CR at a median time of 36 months (range 10-64 months) post-transplant. In the other two patients reasons for failure included relapse of Hodgkin's disease (one patient) and death due to interstitial pneumonitis secondary to carmustine therapy. These patients were compared with a historical control group consisting of 24 patients with the same poor prognostic factors, who achieved CR with MOPP/ABVD and did not receive other treatment. Eight out of 24 patients (33%) remain alive and well in unmaintained CR at a median time of 42 months (range 19-83 months). The administration of MOPP/ABVD combined with HDC and ABMT was not associated with an increased incidence of major toxicity. The results achieved support the early sequential treatment of a highly effective drug combination followed by HDC/ABMT that can substantially improve the likelihood of cure in these advanced stage very poor prognosis Hodgkin's disease patients.

Allogeneic bone marrow transplantation versus chemotherapy for childhood acute lymphoblastic leukaemia in second remission.

Thirty-six children with acute lymphoblastic leukaemia (ALL) in second remission were treated with conventional chemotherapy or with cyclophosphamide and fractionated total-body irradiation followed by an allogeneic bone marrow transplant; the choice of treatment was dictated by the availability of an HLA-identical sibling. The age, sex, clinical data at presentation of the disease and duration of first remission were comparable for the two groups of patients. In the bone marrow transplantation group two patients died of graft-versus-host disease and five of leukaemia. Ten patients survive, nine disease free, 13-53 months from second remission (6-51 months post-bone marrow transplantation). In the chemotherapy group 14 patients died of leukaemia (2-29 months from second remission) and five survive (22-34 months from second remission). The actuarial survival for patients with bone marrow transplantation is 48% at 4 years as compared with 22% for those of the chemotherapy group (P = 0.04); the actuarial probabilities of being in remission are 58 and 18% in the two groups respectively (P = 0.01). This study confirms that allogeneic bone marrow transplantation is superior to chemotherapy in patients in second remission with ALL and should be considered in the presence of an HLA-identical sibling.

Multivariate analysis of risk factors for survival and relapse in chronic granulocytic leukemia following allogeneic marrow transplantation: impact of disease related variables (Sokal score).

Patients with chronic granulocytic leukemia (CGL) can be classified in different groups according to risk factors at diagnosis (Sokal). The aim of the present study was to assess the impact of Sokal's risk factors in 100 patients with CGL undergoing allogeneic BMT. Patients were in first chronic phase (CP) (n = 65), or with advanced disease (n = 35), grafted from an HLA-identical sibling following conditioning with cyclophosphamide and total body irradiation (TBI). Median follow up for survivors is 1783 days (429-3533 days). Variables recorded at diagnosis to calculate Sokal's prognostic index were: leukocyte, platelet and peripheral blood blast cell counts, age and spleen volume. The median value of the Sokal index was 0.87. Projected survival for all patients at 9 years was 28% (95% confidence limits (CL) 6-49), 48% (34-62) for first CP patients and 15% (0-36) for more than first CP patients (p = 0.04). Survival was 25% and 31% for all patients with a Sokal index of < 0.87/> or = (p = 0.07) and 55% vs 39% for first CP patients only (p = 0.03). The relapse rate was similar for patients with Sokal index < 0.87/> or = (41% vs 39%, p = 0.9) and this was also true for first CP patients (33% vs 26%, p = 0.8). In multivariate analysis, an interval between diagnosis and BMT of > 2 years was the most significant negative predictor for survival for the whole group of patients (p = 0.01) and more so for first CP patients (p = 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporin A and chronic graft versus host disease.

One hundred and seventeen patients undergoing allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (n = 18) or leukemia (n = 99) who were alive on day +180, were analysed for the incidence and severity of chronic graft-versus-host disease (cGVHD), developing before or after discontinuation of cyclosporin A (CSA). All patients received CSA for GVHD prophylaxis for 94 to greater than 988 days post-BMT. cGVHD developed in 74 patients (63%) before CSA discontinuation (de novo n = 12, progression from acute GVHD n = 42, following resolution of acute GVHD n = 20). CSA was discontinued in 112 patients: electively (n = 80), because of toxicity (n = 8), or following relapse of leukemia (n = 24). In five patients CSA was never discontinued. After discontinuation of CSA, progression or de novo cGVHD was seen in 25 patients, with a significant difference in patients treated for more or less than 150 days (8% vs 41%, p = 0.0007). In 15 patients CSA had to be re-instituted and in 14 it could be discontinued a second time. Overall 111/117 (94%) patients have finally discontinued CSA. In conclusion cGVHD will progress or appear de novo in 41% of patients receiving CSA for less and in 8% of those receiving CSA for more than 150 days respectively, indicating that the drug should be administered for at least 5 months post-BMT. Most patients (94%) will eventually become CSA independent.

Early treatment of CMV infections in allogeneic bone marrow transplant recipients with foscarnet or ganciclovir.

Twenty-five patients with hematologic malignancies (n = 21) or aplastic anemia (n = 4) undergoing an allogeneic BMT from an HLA-identical sibling developed cytomegalovirus (CMV) antigenemia at a mean interval from BMT of 41 days (range 16-141 days). All patients were treated at the time of antigenemia in the absence of other signs of CMV disease with ganciclovir (n = 13) or foscarnet (n = 12) if the WBC count was < 2.5 x 10(9)/l or the patient had aplastic anemia. The two groups were comparable for age, sex and disease status. There were more patients receiving T cell-depleted grafts in the foscarnet group (58% vs 15%, p = 0.003). The first course of treatment was planned to last a minimum of 10 days: foscarnet was given at 180 mg/kg/day, and ganciclovir at 10 mg/kg/day. Patients still showing pp65-positive cells continued treatment in the absence of adverse effects such as cytopenia and/or increased creatinine levels. Maintenance treatment was given for 3-4 weeks. End-points of the study were (1) clearing of CMV antigenemia, (2) tolerance and side-effects, and (3) progression to CMV disease. Both agents were effective in clearing CMV antigenemia: 14 of 25 patients were CMV antigen-negative by day 14 of treatment and all surviving patients were negative by day +50. Renal toxicity was seen mainly in the foscarnet group but caused discontinuation of the drug only in one patient. Myelotoxicity was seen in the ganciclovir group and again could be controlled in 12 of 13 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

CMV prophylaxis with foscarnet in allogeneic bone marrow transplant recipients at high risk of developing CMV infections.

Eleven patients underwent bone marrow transplant (BMT) from an HLA-identical sibling following single dose total body irradiation (TBI), with in vivo and ex vivo T cell depletion (TCD). In spite of CMV prophylaxis with acyclovir and high-dose i.v. Ig, 10 of 11 patients developed CMV antigenemia, at a median interval from BMT of 34 days (range 16-72 days) and five died with CMV disease. Foscarnet was then given prophylactically in 11 additional TCD patients to test whether we could (1) prevent CMV reactivation, and (2) reduce transplant-related mortality. Foscarnet was given daily from days +10 to +15 (180 mg/kg/day), then thrice weekly (90 mg/kg/day) until day +100. Five patients developed CMV antigenemia at a median interval from BMT of 42 days (range 16-65 days); one progressed to CMV pneumonitis and died. The risk of developing CMV antigenemia within day 100 is currently 91% for the historical control group and 45% for the foscarnet group (p = 0.005). At diagnosis of CMV, the median number of CMV antigen-positive cells was 6.5 (range 1-13) vs 1 (range 1-5) in acyclovir vs foscarnet patients (p = 0.02) and the median highest number of CMV antigen-positive cells was 7 (range 3-110) vs 1 (range 1-12), respectively, (p = 0.03). The actuarial 1 year transplant-related mortality (TRM) is 49% and 13% in the two groups (p = 0.08). This study suggests that foscarnet prophylaxis starting on day +10 post-BMT may be helpful in reducing the risk of CMV disease and early mortality following TCD BMT.

Allogeneic bone marrow transplantation for acute myeloid leukemia in first complete remission: the effect of FAB classification and GVHD prophylaxis.

Ninety-one patients with de novo acute myeloid leukemia (AML) in first complete remission (CR) undergoing an HLA-identical sibling BMT and with a minimum follow-up of 12 months were analyzed for disease-related and transplant-related variables predicting survival and relapse. The overall actuarial 5 year survival is 53% and the relapse rate 29%, with a medium follow-up for surviving patients of 1552 days (range 365-4094 days). In univariate analysis the following variables were found to be associated with an increased risk of failure: high-dose cyclosporin (CsA), M4-M6 FAB subtype and a long interval (> or = 180 days) between diagnosis and BMT. Other disease-related variables at presentation were not significant, including WBC count > 50 x 10(9)/l, marrow blasts < 70%, time to enter remission > 40 days and > 2 courses to enter remission. Survival was 58% vs 43% for M1-M3 vs M4-M6 FAB subtypes (p = 0.03) and 71% vs 42% for low-dose vs high-dose CsA (p = 0.01). A multivariate analysis was then run separately on survival, relapse and transplant related mortality (TRM). Survival was negatively influenced by M4-M6 FAB subtypes (p = 0.009), high-dose CsA (p = 0.03) and a long interval between diagnosis and BMT (p = 0.04). Leukemia relapse was higher in patients receiving high-dose CsA (p = 0.003) and in females (p = 0.04). Transplant-related mortality was higher in FAB M4-M6 patients (p = 0.01) and patients grafted late after diagnosis (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Poor graft function associated with graft-versus-host disease after allogeneic marrow transplantation.

This is a retrospective analysis of marrow function in 171 recipients of an HLA-matched bone marrow transplant (BMT). Only patients with detectable hemopoiesis as indicated by leukocyte counts greater than 1.0 x 10(9)/l and platelet counts greater than 25 x 10(9)/l who were alive on day 30 were entered in the study. Poor marrow function was detected in 24 (14%) patients as indicated by a decrease in the peripheral blood counts to less than 40% of the maximal preceding values post-transplant in association with reduced marrow cellularity. Leukopenia (n = 4), thrombocytopenia (n = 3) or a combination of the two (n = 17) occurred 62 +/- 23 (SEM) days post-transplant and was associated with acute graft-versus-host disease (AGVHD) grade II or more and infection (n = 19) in the absence of clear rejection or persistence/recurrence of malignant disease. A multivariate analysis showed that AGVHD was the major risk factor (p = 0.001) for developing poor graft function. In the 24 patients with poor graft function, hemopoietic recovery was strongly associated with resolution of AGVHD and of infections. Their survival (27%) was the same as survival for other patients matched for GVHD who had no pancytopenia. The causes of death were GVHD (n = 13), pneumonia (n = 3) and infections (n = 1). This study draws attention to a particular type of poor graft function following allogeneic BMT that is characterized by (1) normal timing and quality of engraftment, (2) AGVHD of grade II or greater, (3) progressive and severe pancytopenia, and (4) multiple infections with poor clinical condition.(ABSTRACT TRUNCATED AT 250 WORDS)

CMV-antigenemia after allogeneic bone marrow transplantation: correlation of CMV-antigen positive cell numbers with transplant-related mortality.

One hundred and thirty-four consecutive patients undergoing HLA-identical BMT were prospectively followed on a weekly basis for the development of CMV antigenemia (CMVAg-emia). End-points of the study were (1) incidence, (2) risk factors, and (3) predictive effect on transplant-related mortality (TRM). Fifty-six patients developed CMVAg-emia between day 8-366 (median 40) with an overall actuarial risk of 43%. The median number of positive cells a diagnosis was 4 (range 1-48) the median maximum number was 6.5 (range 1-435). Positive cells are expressed as number/2.5 x 10(5) cells. In multivariate analysis, T cell depletion (TCD) (RR 2.9, P = 0.0009) and acute graft-versus-host disease (RR 2.1, P = 0.01) were the two risk factors predictive for CMVAg-emia. The risk of developing CMV-IP was significantly higher in patients with, as compared to patients without, CMVAg-emia (P = 0.0005) and occurred mostly in patients who received TCD marrow (P = 0.0009) despite treatment with gancyclovir or foscarnet at the time of CMVAg-emia. TRM was 24% in patients not developing CMVAg-emia; it was 21 and 47% in patients with "4" positive cells at diagnosis of CMV (P = 0.008), and 12 vs 54% for patients with "6" positive cells during infection (P = 0.0003). Both were predictive of TRM in multivariate analysis (P = 0.04 and P = 0.002). In conclusion, the risk of developing CMVAg-emia post-allo BMT is influenced by the marrow T cell content and by the occurrence of acute GVHD. High numbers of CMV antigen positive cells are associated with considerable transplant-related mortality, and may therefore identify patients eligible for early aggressive therapy.