Biomedical subjects
Publications and source records attributed to E Conde.
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PURPOSE: To analyze the outcome of patients with multiple myeloma (MM) who were potential candidates for early high-dose therapy (HDT) intensification followed by autotransplantation from a series treated with conventional chemotherapy. PATIENTS AND METHODS: From January 1985 through December 1989, 487 patients with symptomatic MM were entered onto a randomized study to compare melphalan and prednisone (MP) versus vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) /vincristine, carmustine (BCNU), doxorubicin, and prednisone (VBAP). The sub-group of 77 patients who could have been candidates for early intensification with HDT followed by stem-cell support (ie, < 65 years of age, stage II or III disease, performance status < 3, and objective or partial response to initial chemotherapy) are the subjects of this report. RESULTS: Seventy-seven of 487 patients could have been candidates for early intensification. The median age was 56 years (range, 27 to 64). At diagnosis, 12% had abnormal renal function, 16% hypercalcemia, and 42% serum beta 2-microglobulin level > or = 6 mg/L; 62% had stage III disease at diagnosis. Thirty-six patients were initially treated with MP and 41 with VCMP/VBAP. The median response duration to initial chemotherapy was 22 months, and the actuarial probability of being in continued first response at 5 years was 14%. After a median follow-up time of 58 months, 59 patients have died, one was lost to follow-up evaluation, and 17 are still alive 69 to 119 months after initial chemotherapy. The median survival time from initiation of treatment was 60 months and from the time when autotransplantation would be considered, 52 months. The only independent prognostic parameter for survival was renal function at diagnosis. CONCLUSION: The median survival time of patients with MM who are less than 65 years of age and who respond to initial chemotherapy is 5 years. This survival duration is similar to that reported in selected series of patients given early HDT and stresses the importance of ongoing randomized trials to determine the role of HDT in the treatment of younger myeloma patients.
We report four patients with chronic myeloid leukemia (CML) that showed poor graft function after a non-T-depleted bone marrow transplantation (BMT) from an HLA-compatible sibling donor and who were successfully treated with splenectomy. Conditioning was done with cyclophosphamide (CY) and total body irradiation (TBI) without additional splenic irradiation. Three patients had enlarged spleens before BMT. The nucleated cell dose infused ranged from 2.3-3.2 x 10(8)/kg. Bone marrow (BM) examination prior to splenectomy showed BM aplasia (three cases) or hypocellularity (one case). At splenectomy no patient had evidence of cytomegalovirus (CMV) infection or severe acute GVHD; and three patients had moderately enlarged spleens. All patients were transfusion dependent. Complete hematological recovery was obtained in all patients. BM cellularity was normal 1 month after splenectomy. Complete chimerism of donor origin was documented. The four patients are alive (+16 to +58 months after BMT). Thus, in patients with CML, a poor graft function may be successfully corrected by splenectomy.
BACKGROUND: To carry out a study on the prognostic factors in large cell lymphomas (LCL) treated during the last decade and validate the international prognostic index (IPI). METHODS: One hundred twenty-four cases of newly diagnosed LCL, treated from 1978 to 1990, with a mean follow up of 27 months (1-142) were included in the study. The chemotherapy used was: CHOP (65%), ProMACE-CytaBOM (17%) and others (C-MOPP, MACOP-B). RESULTS: Complete remission (CR) was achieved in 71% of the cases and partial in 11%. Logistic analysis allowed the identification of three adverse factors to CR: Ann Arbor stage III, IV (p = 0.004; odds ratio, OR = 0.19), elevated tumoral load (p = 0.006; OR = 0.22) and age > or = 60 years (p = 0.02; OR = 0.31). Recurrence free survival (RFS) at 3 years was 67% (CI 95%; 55-79) with the median not having been achieved. Cox analysis allowed the identification to the ECOG > or = 2 scale as the only independent adverse factor (p = 0.0006; RR = 4.85) while Ann Arbor staging demonstrated marginal influence (p = 0.08). Global survival (GS) at 5 years was 45% (CI 95%; 35-55) with a median of 38 months. Multivariant analysis of independent adverse factors of GS were ECOG scale > or = 2 (p < 0.00001; RR = 6.07), Ann Arbor stage (p = 0.004; RR = 2.64) and hypoalbuminemia (p = 0.01; RR = 2.28). On inclusion of therapeutic response (TR) in the analysis, the factors chosen were absence of CR (p < 0.00001; RR = 9.58) and ECOG > or = 2 (p = 0.0004; RR = 4.24). CONCLUSIONS: Three variables evaluated at diagnosis, general state (ECOG), Ann Arbor stage and albumin, determined the prognosis in this series of large cell lymphoma. A prognostic model was designed from the same with three risk groups. The application of the international prognostic index to this series separated the patients into 4 groups of differentiated prognosis.
The heterogeneous distribution of thyroid C-cells has until now hindered an objective evaluation of changes caused by age or experimental stimuli. To overcome this, a rigorous methodology has been designed to detect variations in shape, size, and number of C-cells throughout development. Using this methodology, we have demonstrated that C-cells do not significantly alter their shape with age. However, their volume increases gradually from 472 microns3 in newborn rats to 1653 microns3 in 120-day-old animals. Over the same time period, the mean number of C-cells within the thyroid gland increased 9-fold (from 1.6 x 10(4) to 1.5 x 10(5), and the number of C-cells per unit area decreased (from 6.15 x 10(4)/mm3 to 2.6 x 10(4)/mm3). We conclude that there are marked variations in size, total number, and number of C-cells per unit area in the rat thyroid gland after birth.
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One hundred and four patients with low grade (9 patients), intermediate grade (31 patients) and high grade (64 patients) non-Hodgkin's lymphoma received an autologous bone marrow transplantation (BMT). Disease status at transplant was first complete remission (CR) in 46 patients, second CR in 14 patients, third CR in 7 patients, chemosensitive disease in 16 patients and chemoresistant disease in 21 patients. Estimated 5 year disease-free survival (DFS) for all 104 patients was 49% (95% confidence interval (CI), 36-63%) with a median follow-up of 24 months. Five year relapse rate for 80 evaluable patients was 26% (95% CI, 14-44%). The 8 year DFS and relapse for the 46 patients transplanted in first CR were 75% (95% CI, 63-82%) and 15% (95% CI, 7-33%), respectively, with a median follow-up of 27 months (range 13-104 months) and a median time to relapse of 5 months (range 4-20 months). In the univariate analysis, variables correlated with DFS were performance status at autologous BMT, disease status at autologous BMT, LDH level at autologous BMT, failure to achieve CR at diagnosis, front-line chemotherapy (1 vs 2 or more regimens) and Working Formulation. Variables correlated with relapse were disease status at autologous BMT, preparative regimen and Coiffer's index at diagnosis. Multivariate analysis showed that performance status was the only independent predictor of DFS and that disease status at autologous BMT was the best relapse predicting variable. In patients transplanted in first CR, the variables correlated with DFS were stage at diagnosis and performance status at autologous BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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To investigate the impact of frozen and non-frozen bone marrow on engraftment kinetics and disease outcome, 94 patients with non-Hodgkin's lymphoma (NHL) autografted with frozen marrow (F group) were retrospectively compared with 38 who received marrow stored at 4 degrees C or 10 degrees C (NF group). The major end points of this study were time to hematopoietic recovery and early toxicity; disease response, disease-free survival (DFS), and relapse rate were also analyzed. Upon comparison of the NF and F groups, no significant differences were found in the period of time required to achieve a granulocyte count higher than 0.5 x 10(9)/l (20 and 22 days, respectively, p = 0.47) or a platelet count higher than 20 x 10(9)/l (28 and 27 days, respectively, p = 0.54). In addition, both groups behaved similarly in respect to toxic death (NF group 13%, F group 22%, p = 0.36), response rate (complete remission rate 78% in both groups), DFS (NF group 48%, F group 49%, p = 0.66), and relapse rate (NF group 30, F group 19%, p = 0.37). This study confirms that nonfrozen bone marrow is useful to support patients with NHL treated with myeloablative therapies.
Eight patients with acute leukemia (AL) and invasive pulmonary aspergillosis (IPA) developing during previous antileukemic therapy underwent BMT (autologous in 6 cases and allogeneic 2). IPA was treated prior to BMT with full doses of amphotericin B, associated with surgical resection in three cases. One patient was treated with amphotericin B and itraconazole. Prior to BMT, seven patients had minimal residual pulmonary lesions. All patients received amphotericin B (0.5 mg/kg/day) during the aplastic period prior to engraftment. One patient died of Gram-negative septic shock before engraftment. Seven patients achieved complete hematological engraftment without any evidence of IPA reactivation. Amphotericin B was well tolerated with only minimal transient renal dysfunction in three patients. Later pulmonary complications related to IPA were observed in only one patient who developed a self-limited episode of hemoptysis. One patient died of CMV pneumonitis and two of leukemia relapse. Four patients survive disease-free and without complications related to IPA. We conclude that the reactivation of correctly treated IPA can be successfully prevented in BMT patients by use of prophylactic amphotericin B. With this approach, prior IPA is not a contraindication to BMT.
The development of calcitonin cells (C-cells) was investigated in rat thyroid glands from birth to 120 days, using an immunoperoxidase technique and a point-counting method. The proportion of C-cells to follicular cells was 4.5% on the day of birth and increased progressively to 10.4% by 120 days. The highest density of C-cells was noted in the mid-region of the lobes along a longitudinal axis. The caudal and cephalic regions of the lobes contained smaller numbers of C-cells. The C-cells tended to be more numerous in the posterior aspects of the lobes. Although the numbers of C-cells in 120-day-old animal were markedly increased as compared to animals at the time of birth, the cell distributions within the glands were similar at all ages.
A systematic immunohistochemical study of the ultimobranchial tubule (UBT) has been carried out in 45 Wistar rats of different ages (0, 5, 10, 15, 20, 25, 30, 60 and 120 days). The existence of calcitonin immunoreactive cells in the UBT wall has been demonstrated in a 5-days old rat. In addition, immunohistochemical studies for thyroglobulin revealed positive staining in follicular cells connected to the UBT and, occasionally, in isolated cells lying within solid clusters from the UBT. These last results together with the continued and repeated existence of numerous mitosis and PAS (+) microfollicles, apparently rising from the UBT, support the hypothesis that the ultimobranchial body (UBB) may contribute partially to the formation of a part of the follicular component.
A study on thyroid glands of Wistar rats of ages ranging from 1 to 120 days was carried out. The glands were serially sectioned and stained for calcitonin using the peroxidase antiperoxidase method. All the thyroids contained ultimobranchial follicles (UBF) located partially embedded among the usual follicles but in a 5-day-old rat this structure showed an unusual position in the interstitium of connective tissue between the cartilage of the trachea and the thyroid gland. We have observed in the wall of that UBF the presence not only of resting C cells but also mitotic figures of C cells. Furthermore, on the opposite side of the same UBF an active area of formation of thyroid follicles was found. These observations provided the first evidence of the contribution of the UBF in the formation of C cells during the postnatal life of the rat. Furthermore, it is suggested that some C cells may share a common origin with ultimobranchially derived follicular cells.
This paper presents the results of investigations into the mitotic rates of thyroid endocrine cells in normal postnatal rats, aged 1-120 days. Our study revealed considerable age-dependent shifts in the mean mitotic activity of follicular cells and C-cells. The maximum indices of endocrine cell renewal were reached during the first 10 days of life, decreasing gradually and significantly until 25 days. At 1 month, there was a significant recuperation of the division rate for both cell types, which declined in the adult rat. These results mean that the proliferation of C-cells and follicular cells is inversely proportional to age. The preferential zone of localization of mitoses of both cell types is the central region of the thyroid lobe. The present paper provides new evidence for the postnatal origin of C-cells and follicular cells from the preexisting endocrine cells.
BACKGROUND: Initially, the aim of the present study was to evaluate the incidence and implicated organisms in the infections in patients receiving a bone marrow transplants (BMT). METHODS: 194 febrile episodes (FE) were evaluated in 115 patients having received a BMT between 1980 and 1987. The analysis was carried out at three different moments: during the period of most marked neutropenia (period I) to the 100th day after BMT (period II) and beyond the 100th day (period III). RESULTS: The unequivocal confirmation that FE was infective was found in 62% of cases (confirmation was microbiological in 46% and clinical in 16%), while 31% of FE were considered as possible infections and the remaining 7% as doubtful infections. The causative organisms were bacteria (73%), viruses (10%), fungi (8%), and combinations of them (polymicrobial infections) (9%). Gram negative and Gram positive organisms were more common, respectively, in period I and in periods II and III (p = 0.02). Bacteremia was the commonest cause of confirmed infection. The overall mortality rate due to infection was 18%. There was a remarkably high mortality from pneumonia (54%) and a low mortality in patients with sepsis (6%) (p less than 0.0001). The number of FE was lower in patients with autografts than those with allografts (p = 0.08). 33% of the FE in patients with allografts were coincident with acute or chronic graft-versus-host disease, and in two thirds of them infections was confirmed. CONCLUSIONS: Infection represents a major complication of BMT. The different antimicrobial treatments used in association with bone marrow grafting allowed us to control most FEs. Pneumonia was the most severe infective localization and the leading cause of death. Mortality rate due to sepsis was small.
The present histometric study is on thyroid glands of Wistar rats ranging in age from 0 to 120 days. The mean volume of one lobe of the thyroid in 4-month-old animals was some 22-, 10-, 5-, and 3-fold greater, respectively, than the volumes in the newborn, 5-, 10-, and 30-day-old rats. At 4 months of age the mean length of the lobe was 3 times greater than at birth. The volumetric fractions (Vv) of the different histological components (follicular cells, C-cells, colloid, and interstitial tissue) changed considerably in the course of development. The Vv of follicular cells diminished from 61.4% at birth to 37.2% at 4 months. C-cells increased from 2.9% in the newborn to 4% at 15 days, with no further significant change at 4 months. Colloid and stroma together represented 35.7% at birth, increasing to 58.5% at 120 days. In the course of the first 4 months of life, the absolute volumes occupied by follicular cells, C-cells, colloid, and stroma increased 13.25, 30.75, 38.6, and 33.7 times, respectively; these changes reflect the variations that occur in the volume of the gland and the Vv throughout postnatal development.
Theoretical considerations and preliminary results of clinical trials support the earlier use of autologous bone marrow transplantation (ABMT) in poor prognosis non-Hodgkin's lymphoma (NHL). A prognostic analysis of 50 patients with intermediate or high grade NHL younger than 60 years, who achieved at least one complete remission and were not treated with BMT, was performed. Patients with bulky tumor at diagnosis and/or serum LDH greater than or equal to 600 U/l do poorly with conventional chemotherapy. Twelve patients with these high-risk initial characteristics in first complete remission (CR) and six patients in second or third CR were treated with cyclophosphamide (60 mg/kg x 2) and total body irradiation (1000-1200 cGy) followed by ABMT. Overall disease-free survival was 65% at a median follow-up of 35 months. No differences were found between the first and later CR patients. The rate of toxic death was 11%. Disease-free survival after first CR was better for 1st CR ABMT patients than for a historical chemotherapy control group with similar poor prognosis features (p = 0.008). These results support the use of ABMT in selected, high-risk NHL patients in first CR.