Cataracts after total body irradiation and bone marrow transplantation in patients with acute leukemia in complete remission: a study of the European Group for Blood and Marrow Transplantation

PURPOSE: Advances in bone marrow transplantation (BMT) have consistently improved long-term survival. Therefore, evaluation of late complications such as cataracts is of paramount importance. METHODS AND MATERIALS: We analyzed data of 2149 patients from the EBMT registry. A cohort of 1063 patients were evaluable for survival and ophthalmologic status after transplant for acute leukemia (AL) in first or second complete remission. Conditioning therapy included either single-dose total body irradiation (STBI) or fractionated TBI (FTBI) grouped in different dose rates (low: LDR < or = 0.04 Gy/min; high: HDR > 0.04 Gy/min). RESULTS: The overall 10-year estimated cataract incidence (ECI) was 50%. It was 60% in the STBI group, 43% in the FTBI group < or = 6 fractions, and 7% in the FTBI group > 6 fractions (p < 10(-4)). It was significantly lower (30%) in the LDR than in the HDR groups (59%;p < 10(-4)). Patients receiving heparin for veno-occlusive disease prophylaxis had fewer cataracts than those who did not (10-year ECI: 33% vs. 53%, respectively;p = 0.04). The 10-year ECI was 65% in the allogeneic vs. 46% in the autologous BMT patients (p = 0.0018). Factors independently associated with an increased risk of cataract were an older age (> 23 years), higher dose rate (> 0.04 Gy/min), allogeneic BMT, and steroid administration (> 100 days). The use of FTBI was associated with a decreased risk of cataract. Heparin administration was a protective factor in patients receiving STBI. In terms of cataract surgery, the unfavorable factors for requiring surgery were: age > 23 yr, STBI, dose rate > 0.04 Gy/min, chronic graft-vs.-host disease (cGvHD), and absence of heparin administration. Among the patients who required cataract surgery (111 out of 257), secondary posterior capsular opacification was observed in 15.7%. CONCLUSION: High dose rate and STBI are the main risk factors for cataract development and the need for surgery, and the administration of heparin has a protective role in cataractogenesis.     

Alprazolam as an alternative to low-dose haloperidol in older, cognitively impaired nursing facility patients

BACKGROUND: Using unrelated bone marrow, there is an increased risk of graft-versus-host disease (GVHD). METHODS: HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow was given to 132 patients. The diagnoses included chronic myeloid leukemia (n=43), acute lymphoblastic leukemia (n=29), acute myeloid leukemia (n=27), myelodysplastic syndrome (n=4), lymphoma (n=3), myeloma (n=1), myelofibrosis (n=1), severe aplastic anemia (n=12), and metabolic disorders (n=12). The median age was 25 years (range 1-55 years). HLA class I was typed serologically, and class II was typed by polymerase chain reaction using sequence-specific primer pairs. Immunosuppression consisted of antithymocyte globulin or OKT3 for 5 days before transplantation and methotrexate combined with cyclosporine. RESULTS: Engraftment was seen in 127 of 132 patients (96%). Bacteremia occurred in 47%, cytomegalovirus (CMV) infection in 49%, and CMV disease in 8%. The cumulative incidences of acute GVHD > or = grade II and of chronic GVHD were 23% and 50%, respectively. The 5-year transplant-related mortality rate was 39%. The overall 5-year patient survival rate was 49%; in patients with metabolic disorders and severe aplastic anemia, it was 61% and 48%, respectively. The disease-free survival rate was 47% in patients with hematological malignancies in first remission or first chronic phase and 38% in patients with more advanced disease (P=0.04). Acute GVHD was associated with early engraftment of white blood count (P=0.02). Poor outcome in multivariate analysis was associated with acute myeloid leukemia (P=0.01) and CMV disease (P=0.04). CONCLUSION: Using HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow and immunosuppression with antithymocyte globulin, methotrexate, and cyclosporine, the probability of GVHD was low and survival was favorable.     

Effects of adenosine, ATP, and UTP on chloride secretion by epithelia explanted from fetal rat lung

To determine the role of intensive chemotherapy and allogeneic bone marrow transplantation (BMT) in treatment of refractory anemia with excess of blasts (RAEB) or RAEB-t (in transformation), the outcome of 37 consecutive children, 12 with RAEB and 25 with RAEB-t, diagnosed between 1985 and 1995 was analyzed. Fourteen patients received intensive chemotherapy according to the AML-BFM protocols 83, 87, or 93 (group 1). Seven patients were treated less intensively with the 6-week consolidation phase as induction (group 2). Allogeneic BMT was performed in 10 children of group 1 and 2 after, and in eight (group 3) without prior chemotherapy. Eight children received minimal or no chemotherapy (group 4). Of 21 children (groups 1 and 2) 17 (81%) achieved complete or partial remission after chemotherapy, 12 of them (10 of group 1) remained in remission, eight after BMT. Five-year survival in 29 children treated intensively (groups 1-3) was 46%, SE 12%. Two of the other eight children (group 4) remained alive, one after spontaneous remission. Outcome after BMT was related to the blast count in the bone marrow prior to BMT. None of 10 children (including two with minimal or no chemotherapy) with < or = 12% blasts before BMT relapsed, in contrast to five of eight patients with a higher blast count (P log rank 0.02). We conclude that a substantial number of children with RAEB or RAEB-t can achieve remission with intensive AML-specific chemotherapy. In patients responding to intensive chemotherapy an increase in long-term survival after allogeneic BMT can be expected.     

ALL R-87 protocol in the treatment of children with acute lymphoblastic leukaemia in early bone marrow relapse

Seventy-three children with acute lymphoblastic leukaemia (ALL) in first bone marrow (BM) relapse, occurring within 30 months from complete remission (CR), were enrolled in an Italian cooperative study (ALL R-87 protocol). This treatment programme consisted of an induction phase with intermediate-dose cytarabine (IDARA-C) plus idarubicin (IDA) and prednisone (PDN), followed by a multidrug consolidation therapy and bone marrow transplant (BMT). 55/73 children achieved CR (75.3%); 15 (20.5%) failed to respond and three (4.2%) died during induction. The response rate was significantly higher for children with a first CR duration > or = 12 months (P=0.0005) and for those with a white blood cell (WBC) count at relapse < 20 x 10(9)/l (P=0.004). The estimated disease-free survival (DFS +/- SE) at 82 months was 0.18 +/- 0.05 for all responders, and 0.70 +/- 0.14 for allotransplanted patients versus 0.05 +/- 0.05 for those autografted (P=0.001). The estimated probabilities of survival +/- SE and event-free survival (EFS +/- SE) at 83 months were 0.16 +/- 0.07 and 0.13 +/- 0.04, respectively. for all enrolled children. Univariate analysis showed that age < 10 years at initial diagnosis and B-lineage immunophenotype favourably influenced both DFS (P=0.001) and EFS probabilities (P=0.0014 and P=0.012, respectively), whereas a first CR duration > or = 12 months and a WBC count at relapse < 20 x 10(9)/l were associated only with a better EFS rate (P=0.026 and P=0.004, respectively). Our results show the efficacy of the IDA plus IDARA-C schedule used in the ALL R-87 protocol in high-risk relapsed ALL children. Allogeneic BMT proved effective for patients with an HLA sibling donor. In a multivariate analysis, age > or = 10 years at initial diagnosis (P=0.016) and WBC count at relapse > or = 20 x 10(9)/l (P=0.048) were independently associated with a worse disease outcome.     

Early neurologic complications following allogeneic bone marrow transplant for leukemia: a prospective study

BACKGROUND: Bone marrow transplant (BMT) is used for both neoplastic and nonneoplastic diseases. Following BMT, particularly during the first 3 months, patients have a number of neurologic complications. We evaluated the early neurologic complications following BMT and their influence on survival. METHODS: We prospectively followed 115 consecutive patients having BMT for leukemia, for a median period of 90 days after transplantation. RESULTS: Sixty-four patients (56%) had neurologic complications. Sixteen developed more than one complication. Twenty-seven patients (25%) had major neurologic complications: metabolic encephalopathy (8), seizures (8), psychiatric symptoms (3), cerebral hemorrhage (1), cerebral abscess (1), leukemic meningitis (1), peripheral neuropathies (5), and myopathies (2). Forty patients (35%) had minor complications, including headache (16) and tremor (31). Major neurologic complications occurred after engraftment in most patients. Metabolic encephalopathy correlated with graft-versus-host disease (GVHD) (p < 0.03). Seven percent of patients had generalized seizures that occurred without signs of structural cerebral lesions. Probability of survival at day 90 was lower in patients with than in those without major central nervous system complications (63% versus 87.5%, p < 0.01). CONCLUSIONS: Neurologic complications are frequent during the first 3 months following BMT and affect patient survival. Drug neurotoxicity and acute GVHD are the main factors influencing their occurrence.     

Prognostic factors in bone marrow transplantation for beta thalassemia major: experiences from Iran

This study concerns the effects of several pre-transplant features on outcome for patients with beta thalassemia major who underwent bone marrow transplantation (BMT). Seventy patients with beta thalassemia major underwent bone marrow transplantation during the period 1991-1997 in Shariati Hospital in Tehran, Iran. The survival and rejection curves levelled off at 8 and 18 months after transplantation at 82.6% and 11.4%, respectively. Pre-transplant clinical features (age, serum ferritin, portal fibrosis, hepatomegaly and quality of chelation therapy) were examined for their effects on survival and recurrence of thalassemia in this group of patients who were less than 16 years old. Increasing age, presence of portal fibrosis and increasing serum ferritin were significantly associated with reduced probability of survival (P = 0.0047, P = 0.016 and P = 0.024, respectively). Hepatomegaly and inadequate pre-transplant chelation therapy which were documented as poor prognostic factors in previous studies, were not evaluable in this study. We also showed the benefits of transplanting more than 5.5 x 10(8)/kg cells in this group of patients with no increase in complications.     

Unrelated donor marrow transplantation for chronic myelogenous leukaemia

Between January 1989 and July 1995 the search for an unrelated donor (UD) was started for 379 consecutive Italian patients with Philadelphia positive (Ph+) chronic myelogenous leukaemia (CML). 89 (23%) were transplanted. The overall probability of transplant before and after December 1991 was 16% and 49%, respectively (P=0.0001), and average interval between search activation and graft was 23 months and 13 months, respectively (P=0.0001). Disease-free survival (DFS) following 60 consecutive transplants performed before February 1996 was 41.5% at 48 months and was 64% for patients grafted after January 1993. In univariate analysis, five variables had a favourable effect on DFS: year of bone marrow transplantation (BMT) after 1993 (P=0.0002), HLA-DRB1 donor/recipient (D/R) match (P=0.0006), total body irradiation (TBI) containing regimen (P=0.0006), graft-versus-host disease (GvHD) prophylaxis including 'early' cyclosporin before the transplant, and a marrow cell dose > 3 x 10(8)/kg of recipient body weight (P=0.04). Multivariate analysis confirmed that HLA identity (P=0.006), TBI-containing regimen (P=0.0001) and 'early cyclosporin' (P=0.04) were associated with higher DFS. Transplant-related mortality (TRM) was 67% in patients grafted before January 1993 and 30% in patients grafted subsequently (P=0.002). Multivariate analysis confirmed DRB1 identity (P=0.03) and TBI-containing regimen (P=0.0005) to be independent factors predictive of low TRM. This suggests that the outcome of patients transplanted from an HLA DRB1 matched donor, after a TBI-containing preparative regimen, is similar to results recently reported in patients transplanted from geno-identical siblings. These results indicate that the search should be initiated at diagnosis for patients < 45 years of age and UD BMT should be considered early in the disease course for those with an available DRB1-matched unrelated donor.     

Levels of the terminal complement complex, C3a-desArg and C1-inhibitor in adult patients with capillary leak syndrome following bone marrow transplantation

Capillary leak syndrome (CLS) is a severe complication after bone marrow transplantation (BMT). To investigate whether there is a pathogenetic role of the complement system, we monitored the levels of the terminal complement complex C5b-9 (TCC) and C3a-desArg as indicators of an activation of the complement system and the inhibitor of the classical pathway of the complement cascade, C1 inhibitor (C1-INH), in 48 bone marrow transplant recipients from 1 week before to 5 weeks after transplantation. Capillary leak syndrome developed in 7 out of 48 patients between days 1 and 12 after BMT. Complement activation as indicated by TCC levels was more pronounced in patients with CLS (n = 7) from day -8 to +28 (p < 0.05; day -1) and the elevation of TCC levels lasted longer in CLS patients (peak day 21) than in patients without this complication (peak day 7). Mean C3a-desArg levels were highest in patients with CLS reaching a peak at day 7. During the early posttransplant period a significant elevation of C1-INH levels (p < 0.01 and p < 0.05 respectively) compared with baseline levels (day -8) was found in patients with and without CLS, which was more pronounced in those patients with CLS (p < 0.05). Although we could not observe an absolute C1-INH deficiency as compared to healthy individuals our data support the presence of a relative deficiency of the inhibitor which might explain the reported beneficial effects of C1-INH substitution in BMT related CLS.     

Tissue-separating capacity of growth cartilages

During 1989, 28 centers of the Association for Academic Research in Vascular Surgery (AURC) reported all cases involving patients with infrarenal abdominal aortic aneurysm (AAA) who reached the operating room alive. In a total series of 1107 procedures, 834 were performed electively. During 1993 and 1994, an effort was made to contact and, if possible re-examine the 794 (95.2%) patients who survived these elective procedures in order to establish survival curves, determine the causes of late death, and ascertain the predictive value for long-term survival of 628 perioperative variables recorded in 1989. Survival curves were calculated using the actuarial and Kaplan-Meier methods and compared with those obtained from national statistical records in a control population matched for age and sex. Variables with potential predictive value for late death were selected by univariate statistical analysis using either the chi2 or student t-test. In the group of 794 (92.5%) patients who survived elective AAA repair in 1989, survival rates were 93.9 +/- 1.8% at 1 year, 89.5 +/- 3.2% at 2 years, 83.5 +/- 3.2% at 3 years, 77.6 +/- 3.9% at 4 years, and 66.9 +/- 10.6% at 5 years. These rates were significantly lower than those observed in the control population. The mean annual death rate from cardiovascular disease was 1.8%, which was higher than in the control population matched for age and sex. Analysis using the Cox proportional risk model showed that the following variables were significant, independent predictors of late death: diameter of aneurysm (p < 0.02), choice of surgical approach in function of general status (p < 0.02), left ventricular insufficiency (p < 0.02), age (p < 0.02), carotid artery occlusion (p < 0.03), use of a surgical approach other than lobotomy (p < 0.04), cardiac arrhythmia (p < 0.04), duration of aortic clamping (p < 0.05), ECG evidence of myocardial ischemia (p < 0.05), abnormality at the upper limit of the aneurysm (p < 0.05), and advanced renal insufficiency (p < 0.05). Life expectancy in patients that undergo successful AAA repair is lower than in the general population. Although death is often unrelated to AAA or the repair procedure, the incidence of morbidity due to cardiovascular disease is higher than in a control population matched for age and sex. These findings suggest that better management of concurrent cardiovascular disease during the perioperative period and long-term follow-up holds the key to improving life expectancy in patients undergoing AAA repair.     

Bone marrow transplantation for adults with acute leukaemia and 11q23 chromosomal abnormalities

Adults with acute leukaemia and abnormalities of chromosome 11q23 have a poor prognosis when treated with conventional chemotherapy. To determine whether more intensive therapy can improve outcome for patients with this karyotypic finding, a retrospective analysis of all patients with acute leukaemia and 11q23 abnormalities treated at our centre was performed. 12 patients were treated with conventional chemotherapy alone (CC); 20 patients received high-dose chemo/radiotherapy (HDCT) with autologous (seven patients) or allogeneic (13 patients) bone marrow transplantation (BMT). The treatment-related mortality was 25% [95% Confidence Interval (CI) 7-69%] for the CC group and 46% (CI 25-73%) for the BMT group (P = 0.69). Cumulative risk of leukaemia progression was 89% (CI 61-100%) in the CC patients and 38% (CI 12-69%) in the BMT patients (P = 0.001). The 2-year event-free survival for patients treated with CC was 8% (CI 0-31%) and for patients receiving HDCT and BMT was 34% (CI 14-54%) (P = 0.03). These results confirm that conventional chemotherapy is rarely curative for adults with acute leukaemia and 11q23 abnormalities but that HDCT with BMT can result in long-term survival in a significant proportion of patients.     

In situ hybridization with riboprobes: an overview for veterinary pathologists

Although preliminary reports indicate that fatigue is a common symptom of human immunodeficiency virus (HIV) disease, little empirical research has focused on its prevalence or characteristics among patients with acquired immunodeficiency syndrome (AIDS). We assessed the frequency of fatigue and its medical and psychological correlates, in a cross-sectional survey of ambulatory AIDS patients. Ambulatory patients with AIDS who participated in a study of quality life (N = 427) were classified into fatigue/no fatigue groups based on their responses to fatigue items on the Memorial Symptom Assessment Scale (MSAS) and the AIDS physical symptom checklist. Self-report inventories were also administered to assess psychological distress, depressive symptoms, and overall quality of life. Medical information was elicited through clinical interview and review of medical chart. Fifty-four percent of the patients endorsed both of the fatigue items from the MSAS and the AIDS physical symptom checklists, and were classified as having fatigue. Women were significantly more likely to report fatigue than men (chi square = 5.28, df = 1, P < 0.03), and patients reporting homosexual contact as their transmission risk factor were significantly less likely to report fatigue than were patients reporting injection drug use or heterosexual contact (chi square = 5.13, df = 2, P < 0.03). The presence of fatigue was significantly associated with the number of current AIDS-related physical symptoms [t(425) = 8.00, P < 0.0001], current treatment for HIV-related medical disorders (chi square = 12.51, df = 1, P < 0.0001), anemia [t(174) = -2.35, P < 0.02], and pain (chi square = 36.36, df = 1 P < 0.0001). Patients with fatigue also had significantly poorer physical functioning ability [Karnofsky: t(422) = -6.27, P < 0.0001], as well as greater degree of overall psychological distress and lower quality of life [F(5,418) = 23.79, P < 0.0001], as measured by the Brief Symptom Inventory, Beck Depression Inventory, Beck Hopelessness Scale, Functional Living Inventory for Cancer (modified for AIDS), and the MSAS Psychological Distress Subscale. Fatigue is a common symptom in ambulatory AIDS patients and is associated with significant physical and psychological morbidity.     

Treatment of Ph1-positive chronic myelogenous leukemia in children: comparison between allogeneic bone marrow transplantation and conventional chemotherapy. Spanish Working Party for BMT in Children (GETMON)

BACKGROUND AND OBJECTIVE: To compare the estimated survival and disease-free survival between children with Ph1-positive chronic myeloid leukemia treated with allogeneic bone marrow transplantation or conventional chemotherapy. DESIGN AND METHODS: In this retrospective study we compared the results obtained in a group of 14 children who received allogeneic bone marrow transplantation (BMT) between 1983 and 1993, and another group of 27 children treated with busulfan, hydroxyurea or alpha-interferon during the same time period. Patients were transplanted at a median of 7 months from diagnosis and all except one were in their first chronic phase. Conditioning consisted in total body irradiation and cyclophosphamide in 12 cases, and busulfan was added in two. RESULTS: Of the 14 patients treated with BMT, two died of transplant-related complications and two relapsed 18 and 48 months after the BMT. Ten children remain alive and disease free at a median follow up of 60 months. The probability of DFS at 5 years is 70%. Of the 27 patients treated with chemotherapy, 22 have died at a median of 36 months from diagnosis. The probability of survival at 5 years is 5% versus 83% for the BMT group (p = 0.001). INTERPRETATION AND CONCLUSIONS: Allogeneic BMT is a safe and very effective treatment for Ph-positive CML in children. Patients who have an HLA-identical sibling donor must receive a transplant as soon as possible after being diagnosed.     

Dolichoectasia of the intracranial arteries in patients with first ischemic stroke: a population-based study

OBJECTIVE: The objective of this study was to estimate the frequency of intracranial arterial dolichoectasia among patients with first ischemic stroke and to compare clinical characteristics, survival, and recurrence in those with and without the abnormality. BACKGROUND: Dolichoectasia may cause cerebral infarction by thrombosis, embolism, stenosis, or occlusion of deep penetrating arteries. METHODS: The chi-square, Fisher's exact, and logrank tests were used to compare clinical characteristics, survival, and recurrence for patients with and without dolichoectasia among the 387 residents of Rochester, MN, who had brain CT or MRI for first cerebral infarction from 1985 through 1989. RESULTS: Twelve patients (3.1%) had dolichoectasia. Patients with dolichoectasia were more likely to have had stroke fitting a clinical and radiographic pattern of lacunar infarction than those without (42% and 17% respectively; p=0.04). Dolichoectasia was detected in the vertebrobasilar system in eight patients (66.7%), in the carotid system in two patients (16.7%), and in both circulatory systems in two patients (16.7%). There were no significant differences in the following characteristics among those with and without dolichoectasia: age, sex, hypertension, diabetes, smoking, and preceding transient ischemic attack. Patients with dolichoectasia had better survival (relative risk [RR] for death, 0.26; p=0.04) after first cerebral infarction but higher rates of stroke recurrence (RR, 2.4; p=0.02). CONCLUSIONS: Dolichoectasia is detected in 38 of patients with first cerebral infarction and is associated with better survival but higher rates of stroke recurrence.     

Prognostic significance of B-lineage leukemic cell growth in SCID mice: a Children's Cancer Group Study

Primary leukemic cells isolated from children (N = 681 ) with newly diagnosed B-lineage ALL enrolled on risk-adjusted treatment protocols of the Children's Cancer Group (CCG) were injected via the tail vein into 7-10 week old SCID mice. Leukemic cells from 104 of 681 patients (15.3%) were able to engraft and proliferate in one or more SCID mouse organs. These SCID+ patients were somewhat more likely than SCID patients to be older than 10 years of age (p = 0.03) and have WBC counts >20,000/microL (p = 0.04), but the groups were similar with respect to all other presenting features. Event-free survival (EFS) outcome at 3 years of follow-up was similar for SCID+ patients compared with SCID- patients (79.2%, SD = 5. 1% vs. 84.8%, SD = 2.8%; p = 0.20). Overall survival also was similar between the two groups (p = 0.93). This result was maintained within the subgroups of lower risk (N = 448) and higher risk (N = 233) patients. However, there were trends for poorer outcome among patients whose cells caused overt leukemia in SCID mice and infiltrated either 6 or more organs (p = 0.03), skeletal muscle (p = 0.0003), kidney (p = 0.05), or spleen (p = 0.06). Thus, engraftment of primary leukemic cells in SCID mice was not a significant predictor of outcome for the aggregate population of B-lineage ALL patients, the majority of whom were low risk, treated according to contemporary intensive chemotherapy programs of the CCG. However, development of disseminated overt leukemia and infiltration of SCID mouse skeletal muscle by primary leukemic cells from adjacent bone marrow may reflect a biologically more aggressive disease and identify patients at higher risk for treatment failure.     

Two models of epileptic spike-and-wave rhythm in rats are differently influenced by ethosuximide

One hundred and thirty-seven consecutive patients who received bone marrow or peripheral blood stem cell transplantation were studied retrospectively to identify the risk factors for hepatic veno-occlusive disease (VOD). Of the 137 recipients, twenty (14.6%) patients were diagnosed with VOD using the McDonald's criteria. In these 20 patients with VOD, we analyzed various clinical parameters, including age, sex, HLA status, conditioning regimen, irradiation, immunosuppressive agents, mode of transplantation, history of hepatic dysfunction, pre-transplant hepatic and renal function, infectious episodes, antibiotics use, and serum viral titers. A history of hepatic dysfunction and low levels of pseudocholinesterase before transplantation were found to be statistically significant (P = 0.04 and 0.04). Low levels of pseudocholinesterase were significant by multivariate analysis using the logistic regression model (P = 0.02). These results suggest that pseudocholinesterase levels before transplant are important markers of VOD in patients receiving BMT.     

Unification of protein families

OBJECTIVE: To evaluate the prognostic significance of isolated tumor cells detected by a panel of various monoclonal antibodies. SUMMARY BACKGROUND DATA: Previously, we showed by using immunocytology that cancer cells are frequently found in bone marrow and peritoneal cavity samples of gastrointestinal cancer patients. METHODS: Findings in bone marrow and peritoneal cavity samples were compared and correlated with the 4-year survival rate of 84 gastric and 109 colorectal patients with cancer. RESULTS: Although positive results in the bone marrow showed little prognostic significance, the peritoneal cavity results correlated with the 4-year survival rate (gastric cancer: p = 0.0038; colorectal cancer: p = 0.0079). Additionally, in subgroups of patients with early (gastric cancer: p = 0.02, colorectal cancer: p = 0.48) and advanced (gastric cancer: p = 0.02, colorectal cancer: p < 0.0001) tumor stages, a correlation of immunocytologic findings and the survival rate was seen. CONCLUSIONS: The detection of minimal residual disease in the peritoneal cavity serves as a new prognostic marker.     

Busulfan-based regimens and allogeneic bone marrow transplantation in patients with myelodysplastic syndromes

Preparative regimens containing busulfan (BU) followed by allogeneic bone marrow transplantation (BMT) were used in 27 consecutive patients with myelodysplastic syndromes (MDS). The median age was 33 years (range, 4 to 54). Ten were female and 17 male. Sixteen patients had primary MDS, 11 other patients had antecedent hematologic diseases or developed MDS after cytotoxic and/or radiation therapy. Six patients had leukemic transformation and received antileukemic therapy before BMT. Pre-BMT cytogenetic studies showed complex chromosomal abnormalities in 13 patients, a simple abnormality in 5 patients, and normal chromosome in 8 patients. Three BU-based preparative regimens were used: 1 patient received BU 4 mg/kg orally (PO) daily for 4 days and cyclophosphamide (CY) 50 mg/kg intravenously (IV) daily for 4 days (BUCY-4); 24 patients received BU 4 mg/kg PO daily for 4 days, cytosine arabinoside (ara-C) 2 g/m2 IV every 12 hours for 4 doses, and CY 60 mg/kg IV daily for 2 days (BAC); and 2 patients with preceding Fanconi anemia received BU 2 mg/kg PO daily for 4 days followed by total lymphoid irradiation of 5 Gy. Seventeen of 27 patients are alive with no evidence of disease. Ten patients have died: 2 from hepatic veno-occlusive disease, 3 from sepsis, 1 from a cerebral bleed, 1 from a massive gastrointestinal (GI) bleed associated with acute graft-versus-host disease, 1 from hemolytic uremic syndrome with adult respiratory distress syndrome, 1 from bronchiolitis obliterans, and the only patient who did not engraft died from acute myeloid leukemia. Regimen-related toxicities (RRT) include GI tract (diarrhea, 14; stomatitis, 11), liver (9), cardiac (1), and skin (5). Patients who received a genotypically matched marrow graft had a significantly better disease-free survival (DFS) than patients who received a nongenotypic marrow graft (P = .02). The Kaplan-Meier analysis projects an overall DFS of 56% +/- 13% and 78% +/- 10% for patients who received a genotypically matched marrow graft. With the exception of a child who did not engraft, there was no relapse of MDS or leukemia. Excellent DFS, acceptable RRT, and the ease of administration are advantages of this regimen.     

Pulmonary toxoplasmosis in patients with human immunodeficiency virus infection. 21 cases

OBJECTIVES: Assess expression of pulmonary toxoplasmosis, the second most frequent localization after brain, in patients infected with the human immunodeficiency virus (HIV). METHODS: Twenty-one HIV-infected patients (18M, 3F) were admitted for pulmonary toxoplasmosis between September 1987 and February 1995. Mode of HIV transmission was unprotected homosexual sexual activity (n = 16), intravenous drug abuse (n = 3) and transfusion (n = 2). RESULTS: Isolated pulmonary toxoplasmosis was found in 11 patients. In 10 patients pulmonary toxoplasmosis was associated with cerebral (n = 4), bone marrow (n = 2), ocular (n = 1) and multifocal (n = 3) localizations. Seven patients were admitted for acute pulmonary distress. Fever (reported for 20 patients) and nonproductive cough (reported for 16 patients) were the most common clinical symptoms. Chest roentgenogram revealed bilateral pulmonary infiltrates in 16 (76%) patients. Mean absolute CD4 count was 25 +/- 57 (range 0-110). Serologic evidence of past infection was observed in 18 patients. Serology tests were not done for two patients and negative for one. Two patients presented co-infection with Pneumocystis carinii. Fourteen patients had elevated serum lactic dehydrogenase (LDH) concentration. Among those, 4 patients whose LDH concentration was elevated more than ten fold died of respiratory distress. Patients received pyrimethamine and sulfadiazine (n = 13) or clindamycin (n = 8). Seven patients died during the first month after diagnosis was made. For the other patients, mean survival was 8 months. No relapse of toxoplasmosis was observed. All the patients took a secondary prophylaxis. CONCLUSION: No difference between patient with isolated pulmonary toxoplasmosis and patients with associated extra-pulmonary localization was noted for clinical, biological, radiological presentations and outcome.     

Characteristics of non-participants and reasons for non-participation in a population survey in Kin-Hu, Kinmen

We analyzed the pattern of failure and clinicopathologic factors influencing the disease-free survival of 78 patients who died after macroscopic curative resection for pancreatic cancer. Local recurrence was a component of failure in 56 patients (71.8%) and hepatic recurrence in 48 (61.5%), both accounting for 97% of the total recurrence rate. About 95% of recurrences occurred by 24 months after operation. Median disease-free survival time was 8 months, and cumulative 1-, 3-, and 5-year actuarial disease-free survival rates were 66%, 7%, and 3%, respectively. Multivariate analysis showed that tumor grade (p = 0.04), microscopic radicality of resection (p = 0.04), lymph node status (p = 0.01), and size of the tumor (p = 0.005) were independent predictors of disease-free survival. Patterns of failure and disease-free survival were not statistically influenced by the type of surgical procedure performed. Median survival time from the detection of recurrence until death was 7 months for local recurrence versus 3 months for hepatic or local plus hepatic recurrence (p < 0.05). From our experience and the data collected from the literature, it appears that surgery alone is an inadequate treatment for cure in patients with pancreatic carcinoma. Effective adjuvant therapies are needed to improve locoregional control of pancreatic cancer after surgical resection.