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Biomedical subjects

M Benavides

Publications and source records attributed to M Benavides.

At least 19 recordsLinked to original sources
PubMed2006

Conservative treatment with transurethral resection, neoadjuvant chemotherapy followed by radiochemotherapy in stage T2-3 transitional bladder cancer.

PURPOSE: Organ preservation has been investigated in patients (p) with infiltrating transitional cell carcinoma (TCC) of the bladder over the past decade as an alternative to radical cystectomy. This is a trimodal schedule study, including transurethral resection of bladder tumor (TURB), neoadjuvant chemotherapy and concomitant radiochemotherapy (RTC). PATIENTS AND METHODS: From April 1996 until August 2005, 29 evaluable patients (p) with T2-T3NXM0 bladder cancer were enrolled. After a transurethral resection of bladder tumor (TURB), we administered 2 cycles of induction chemotherapy with CMV (15 p) or Gemcitabine-Cisplatin (14 p) followed by radiotherapy 45 Gy 1.8 Gy/fraction and two cycles of concomitant cisplatin 70 mg/m(2). 2-3 weeks later, a cystoscopy with tumor-site biopsy was performed. If complete histological response, p were treated with consolidation radiotherapy until 64.8 Gy. For p with residual or recurrent tumor, cystectomy was performed. RESULTS: We included 28 men and 1 women (median age 63, range 39-72 years) with PS (ECOG) 0-1. The stage was: 21 p T2; 6 p T3a; and 2 p T3b. Toxicity was higher in CMV compared with Gem- Cis: grade (3/4) neutropenia 4/15 (26%) vs 1/14 (7%); febrile neutropenia 3/15 (20%) vs 1/14 (7%); grade (3/4) trombocytopenia 2/15 (13%) vs 1/14 (7%). Toxicities with concomitant RCT were low-moderate: urocystitis (26%) and enteritis (18%). RESPONSE: microscopically complete TURB was obtained in 20 p (69%), but not in 9 p (31%) (7 microscopic, and 2 macroscopic residual tumor). We found a complete histologic response after induction RCT in 25 p (86%). After a median follow-up of 69.4 months (m) (range: 8-97.7), there were 8 deaths, with a overall survival of 72%. Furthermore 14 of 29 p (48%) were alive with intact bladder, and median survival time with intact bladder was 63.6 m (50.1-77.2); were predictive of best outcome T2 stage vs T3 (p < 0.0001), and complete histologic resection in initial TURB vs residual tumor (p = 0.0004). CONCLUSIONS: Combined treatment provide high response rates and can be offered as an alternative option to radical cystectomy in selected patients with TCC. Patients with T2 stage and complete histologic resection in initial TURB had the best outcome.

Adult↗
PubMed2004

Weekly irinotecan (CPT-11) in 5-FU heavily pretreated and poor-performance-status patients with advanced colorectal cancer.

Irinotecan (CPT-11) is an effective drug in patients with advanced colorectal cancer (CRC). Little is known about its efficacy and safety in previously treated patients with poor performance status. We prospectively evaluated the antitumor efficacy and safety of CPT-11 monotherapy in this setting. Thirty-four patients with poor performance status (Karnofsky score between 60 and 80) and/or progressing on one or more previous 5-FU-based chemotherapy lines for advanced colorectal adenocarcinoma were enrolled in this study. Treatment consisted of irinotecan (CPT-11) at 100 mg/m(2) administered as a 60-min iv infusion every week for four consecutive weeks followed by a 2-wk rest period until disease progression or unacceptable toxicity. The overall objective response rate (WHO criteria) for the 34 patients included was 20.6% [95% confidence interval (CI): 6.3%-34.9%]. Stable disease was obtained in 13 patients (38.2%) and 14 patients (41.2%) progressed. The median time to disease progression was 5.5 mo (range: 0.9-17.5) and the median survival was 8.3 mo (95% CI: 1.7-16.9). Overall, weekly CPT-11 was well tolerated with grade 3/4 neutropenia as the main hematological toxicity (11 patients: 32.4%; 14 infusions: 3.3%), and delayed diarrhea (10 patients: 29.4%; 16 infusions: 3.8%) as the main grade 3/4 non-hematological toxicity. In conclusion, weekly CPT-11 at 100 mg/m(2) for four consecutive weeks followed by a 2-wk rest period showed antitumor efficacy and may be safely administered to heavily pretreated patients with advanced colorectal cancer and a poor performance status. Weekly CPT-11 monotherapy may be considered as a therapeutic option for this population of patients.

Adenocarcinoma↗
PubMed2001

High-dose mitoxantrone and cyclophosphamide without stem cell support in patients with high-risk and advanced breast carcinoma: a Phase II multicentric trial.

BACKGROUND: Currently employed high-dose regimens for patients with breast carcinoma consist mainly of single-cycle combinations of alkylating agents. In a previous Phase I trial, the authors developed a tandem high-dose combination of two cycles of mitoxantrone and cyclophosphamide for the treatment of patients with metastatic breast carcinoma (MBC) and high-risk breast carcinoma (HRBC). Treatment was delivered with granulocyte-colony stimulating factor (G-CSF) but without stem cell support to avoid potential tumor cell reinfusion. The objective was to validate the safety and obtain preliminary efficacy assessment of this combination in a Phase II trial. METHODS: Fifty-three patients were included: 27 patients with MBC and 26 patients with HRBC. After standard induction treatment, patients received two cycles of mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2 separated by a 4-week interval. Patients received G-CSF and ciprofloxacin until hematologic recovery. Follow-up was performed in an outpatient setting. RESULTS: One hundred one of 106 projected cycles (95%) were delivered. The mean dose intensities achieved were mitoxantrone 5.8 mg/m2 per week and cyclophosphamide 933 mg/m2 per week. Infection developed in 46% of the cycles, and platelet transfusions were required in 42%. Nonhematologic toxicity was mainly Grade 3 emesis. There were no toxic deaths. In 17 evaluable patients with MBC, 13 patients (77%) had response improvements, including 7 complete responses (41%). CONCLUSIONS: Treatment with two cycles of mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2 with G-CSF but without stem cell support was well tolerated. The dose intensities achieved approach those obtained with conventional high-dose therapy. This combination warrants further investigation as an alternative to conventional high-dose regimens.

Adult↗
PubMed2000

Microanalysis of enzyme digests of hyaluronan and chondroitin/dermatan sulfate by fluorophore-assisted carbohydrate electrophoresis (FACE).

Hyaluronan and chondroitin/dermatan sulfate are glycosaminoglycans that play major roles in the biomechanical properties of a wide variety of tissues, including cartilage. A chondroitin/dermatan sulfate chain can be divided into three regions: (1) a single linkage region oligosaccharide, through which the chain is attached to its proteoglycan core protein, (2) numerous internal repeat disaccharides, which comprise the bulk of the chain, and (3) a single nonreducing terminal saccharide structure. Each of these regions of a chondroitin/dermatan sulfate chain has its own level of microheterogeneity of structure, which varies with proteoglycan class, tissue source, species, and pathology. We have developed rapid, simple, and sensitive protocols for detection, characterization and quantitation of the saccharide structures from the internal disaccharide and nonreducing terminal regions of hyaluronan and chondroitin/dermatan sulfate chains. These protocols rely on the generation of saccharide structures with free reducing groups by specific enzymatic treatments (hyaluronidase/chondroitinase) which are then quantitatively tagged though their free reducing groups with the fluorescent reporter, 2-aminoacridone. These saccharide structures are further characterized by modification through additional enzymatic (sulfatase) or chemical (mercuric ion) treatments. After separation by fluorophore-assisted carbohydrate electrophoresis, the relative fluorescence in each band is quantitated with a cooled, charge-coupled device camera for analysis. Specifically, the digestion products identified are (1) unsaturated internal Deltadisaccharides including DeltaDiHA, DeltaDi0S, DeltaDi2S, DeltaDi4S, DeltaDi6S, DeltaDi2,4S, DeltaDi2,6S, DeltaDi4,6S, and DeltaDi2,4,6S; (2) saturated nonreducing terminal disaccharides including DiHA, Di0S, Di4S and Di6S; and (3) nonreducing terminal hexosamines including glcNAc, galNAc, 4S-galNAc, 6S-galNAc, and 4, 6S-galNAc.

Acetylgalactosamine↗
PubMed1998

Non-invasive estimation of the circadian rhythm in serum cortisol in patients with ovarian or colorectal cancer.

The variability in toxicity or efficacy of cancer chronotherapy among patients may be due to differences in circadian rhythm. Adequate assessment of circadian rhythm often requires repeated blood sampling over at least a 24-hr period; this cannot be a routine procedure. We attempted to assess the reliability of a 2-timepoint estimate of the 24-hr rhythm of serum cortisol in 19 healthy subjects, 19 women with ovarian cancer and 18 patients with metastatic colorectal cancer. The difference between daily maximum and minimum values (MAX-MIN) was compared with that observed between values at 08.00 and at 16.00 (H8-H16). As significant correlations were found between both variables in all groups, we conclude that the magnitude of circadian changes in serum cortisol may be estimated from blood samples collected at 08.00 and at 16.00. The clinical relevance and the prognostic value of this method of assessment are currently under evaluation in a larger-scale clinical trial.

Adult↗
PubMed1998

Oxaliplatin as single agent in previously untreated colorectal carcinoma patients: a phase II multicentric study.

BACKGROUND: Oxaliplatin is a new cytotoxic agent from the diaminocyclohexane family with proven antitumor activity against colon cancer cell lines. Activity in patients with colorectal carcinoma previously treated with 5-fluorouracil has been studied in three single-agent phase II trials, showing a reproducible response rate of 10%. Here we report a phase II trial with oxaliplatin as a first-line chemotherapy for metastatic colorectal cancer. PATIENTS AND METHODS: Twenty-five patients were entered in the study. All of them had metastatic disease without previous chemotherapy, and at least one lesion had to be measurable by computed tomography (CT). Therapy consisted of a two-hour infusion of oxaliplatin at a dose of 130 mg/m2 every 21 days. RESULTS: The overall response rate determined by investigators was 20% (95% CI, 6.8%-40.7%). Eight patients (32%) had stable disease. The median time to disease progression in responders was six months (range four to nine). The median progression-free survival was four months and median overall survival 14.5 months (95% CI, 10-20 months). The main toxic effects were peripheral neuropathy (92%) and laryngopharyngeal dysesthesia (75%). No severe grade 3-4 neurotoxicities (NCI-CTC) were found. Gastrointestinal and hematological toxicities were mild. CONCLUSIONS: Oxaliplatin is an active agent in first-line chemotherapy for advanced colorectal cancer. It was well tolerated, caused no toxic deaths, had low hematotoxicity, well controlled gastrointestinal toxicity, and frequent but mild peripheral neurological symptoms. Therefore, it is of interest to associate oxaliplatin with other active compounds.

Adenocarcinoma↗
PubMed1996

Disruption of the circadian patterns of serum cortisol in breast and ovarian cancer patients: relationships with tumour marker antigens.

Few data are available on the circadian rhythmicity in cancer patients. Since monitoring the disease usually implies the follow-up of blood concentrations of a number of biological variables, it would be of value to examine the profile of the circadian variations of serum cortisol and tumour marker antigens. This we did in 33 cancer patients (13 breast cancer patients and 20 ovarian cancer patients). The profiles of serum cortisol were documented, since this hormone is considered as a strong marker of circadian rhythms. This study shows that 8 out of 13 breast cancer patients and 15 out of 20 ovarian cancer patients had deeply altered cortisol circadian patterns. The modifications were either high levels along the 24 h scale and/or erratic peaks and troughs and/or flattened profiles. Within 24 h, variations of tumour marker antigens as large as 70% were observed but no typical individual circadian patterns could be found. No relationship between cortisol subgroups and concentration of tumour marker antigens at 8 h could be observed (Kolmogorov-Smirnov's test). The question thus arises as to the origin of these alterations, and whether they are related to a cause or a consequence of the disease, and their possible incidence upon therapeutic designs.

Adult↗
PubMed1995

Rhythm alteration in patients with metastatic breast cancer and poor prognostic factors.

Circulating blood cell counts, serum cortisol, proteins, alkaline phosphatase, carcinoembryonic antigen and CA15.3 displayed significant circadian rhythms in a group of 13 women with metastatic breast cancer. Statistical significance (P < 0.05) was assessed with both analysis of variance and cosinor analysis. All patients had been previously treated with chemo-and/or radiotherapy and/or antiestrogens. All patients had been treatment-free for 1 month prior to the study. Each patient had blood drawn every 4 h for 48 h. Circadian rhythms were examined as a function of performance status, graded according to the World Health Organization, liver involvement and number of metastatic sites. Group circadian rhythms in serum cortisol or proteins were abolished in patients with liver metastases, and were altered in cases of poor performance status. Circulating leukocytes, neutrophils or platelets did not exhibit synchronized circadian rhythmicity in patients with poor performance status or liver metastases. The number of metastatic organs had a minor influence on circadian rhythmicity. These results suggest that rhythm alteration may be associated with both poor performance status and liver metastases in patients with advanced breast cancer. Such alteration of the normal circadian time structure may favor and/or result from cancer spread.

Adult↗
PubMed1995

Reduced expression of platelet surface glycoprotein receptor IIb/IIIa at hyperthermic temperatures.

BACKGROUND: Hyperthermic temperatures exist from the heat dissipation of the implantable energy source of an artificial heart. This procedure as well as therapies for cancer and thermal injuries pose a new medical problem. Among many reported effects of heat on biologic systems, platelet functions such as maximal aggregation and adhesion are known to be reduced. Using flow cytometry, we have studied platelet dysfunction at elevated temperatures and have gained a mechanistic comprehension of the loss of platelet function. EXPERIMENTAL DESIGN: Platelet rich plasma was incubated at differing temperatures for 1 hour. Immediately after, the platelets were stained using mAb against glycoprotein IIb/IIIa (GPIIb-IIIa) (CD41a) and other platelet surface glycoproteins (GP) involved in aggregation and adhesion. Relative fluorescence intensity was measured using single-labeled, laser flow cytometry to determine changes in GP surface expression. In addition, scanning electron microscopy was used to evaluate morphologic changes. RESULTS: Hyperthermic temperatures between 40 and 44 degrees C significantly lowered the mAb cell surface binding in vitro of GP that participate in aggregation and adhesion. The most dramatic temperature-dependent loss of mAb binding was demonstrated by anti-GPIIb-IIIa, the mAb against the fibrinogen receptor. mAb binding to this receptor at 44 degrees C was decreased to 6.2% of a base-line fluorescence intensity of 654 (arbitrary units). The ADP-induced aggregation of platelets incubated at the same temperature also decreased to 2.1% of maximum aggregation. Other mAb, such as those against the von Willebrand factor receptor (GPIb) (CD42b), the thrombospondin receptor (GPIV) (CD36), and GPIIIa (CD61), also showed statistically significant reduction of mAb binding but to a lesser degree. Finally, scanning electron microscopy as well as side-scatter density plots from flow cytometry revealed that platelets became more spherical after incubation at 44 degrees C. CONCLUSIONS: The significant reduction in mAb binding correlates with functional impairment exhibited during hyperthermic incubation. Our results support the loss of binding ability of surface GP that are involved in aggregation and adhesion as a mechanism of platelet dysfunction upon heating. GPIIb-IIIa appeared the most susceptible to heat and the principal agent in thermal induced loss of platelet function. Significant morphologic changes at 44 degrees C, the critical temperature at which ADP-induced aggregation ceases, may contribute as well.

Antibodies, Monoclonal↗
PubMed1991

Retinoic acid in mono- or combined differentiation therapy of myelodysplasia and acute promyelocytic leukemia.

Myelodysplastic preleukemic syndromes (MDPS) and acute promyelocytic leukemia (APL) share a surprising in vivo sensitivity to the hormonally acting 13 cis or all trans retinoic acids (transRA). Here we show that transRA as a monotherapeutic agent induced a stable remission in APL at the third relapse. In MDPS, treatment with prednisone and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25D3) 13 cis RA induced a long-lasting hematological remission. Initially both patients had an impaired BM microenvironment which regenerated on retinoid therapy as judged by reappearance of the Hematon fraction in the BM aspirates. Our preclinical experiments using long-term liquid BM cultures (LTBMC) indicated that several individual patterns of growth and differentiation responses can be induced by combinations of transRA, 1 alpha,25D3 and hemopoietic growth factors (HGFs). The biological responses may vary from complete clonal extinction to a significant growth stimulation of the leukemic blast cell populations. These results further support the importance of preclinical studies in selecting "good" responders for, and excluding "poor" responders from protocols using differentiation therapy.

Bone Marrow↗
PubMed1990

Chemotherapy of advanced ovarian cancer with 4'-O-tetrahydropyranyl doxorubicin and cisplatin: a randomized phase II trial with an evaluation of circadian timing and dose-intensity.

The efficacy and toxicity of the new anthracycline, 4'-0-tetrahydropyranyl doxorubicin (THP) (50 mg/m2 intravenous [IV] bolus) in association with cisplatin (100 mg/m2 IV as a 4-hour infusion) was assessed in 31 patients with advanced ovarian carcinoma. Twenty-eight patients were assessable for toxicity among whom 25 were assessable for response (International Federation of Gynecology and Obstetrics [FIGO] stage IIIa, four patients; IIIb, 15 patients; IV, six patients). Nine patients had received prior treatment. Patients were randomized to receive schedule (sch) A (THP at 6 hours, then cisplatin from 16 to 20 hours) or sch B (THP at 18 hours, then cisplatin from 4 to 8 hours). Sch A was hypothesized as less toxic since THP was best tolerated in the late rest span and cisplatin near the middle of the activity span in experimental studies. The rate of clinical complete response (CR) was 52%, that of partial response (PR) was 12%, and the overall clinical response rate (CR plus PR) was 64% (sch A, 73%; sch B, 57%). Median progression-free survival and survival times were, respectively, 10 and 19 months. Of 12 patients in clinical CR evaluated at second-look laparotomy, four had a pathological CR (33%), and three had microscopic residual disease (MD). The overall rate of pathological CR was 16%. Sch A was associated with less neutropenia (P = .10), thrombocytopenia (P less than .01), anemia (P less than .01), and renal toxicity (P less than .05) than sch B. Of four patients withdrawn for toxicity, three were on sch B (one death). Mean dose intensities (DIs) of THP and cisplatin, respectively, decreased by 30% and 47% over the five initial courses. Such decrease was significantly more pronounced for sch B than for sch A in previously untreated patients (P from 2-way analysis of variance [ANOVA] less than .01). THP-cisplatin is active against advanced ovarian cancer, and its toxicities can be significantly decreased by dosing THP in the early morning and cisplatin in the late afternoon as compared with THP in the evening and cisplatin the next morning.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Hematon, a multicellular functional unit in normal human bone marrow: structural organization, hemopoietic activity, and its relationship to myelodysplasia and myeloid leukemias.

An increasing amount of data provides strong evidence for the complex multifactorial control of primary hemopoietic functions. Here we present a new multicellular functional unit, the Hematon, isolated from the light-density floating fraction of normal human bone marrow (BM) aspirates. The Hematon is organized in a compact, three-dimensional spheroid complex from central adipocytes, fibroblastoid cells, and resident macrophages that compartmentalize myeloid, erythroid, and megakaryocyte progenitor cells and their progenies. The Hematon fraction is more than twofold more abundant in progenitor cells when compared to the mononuclear cell (MNC) fraction as gauged by cytological techniques and by analysis of granulocyte-macrophage colony-forming unit (GM-CFU) populations. Individual Hematons may produce, within 2-3 weeks, up to 50,000 hemopoietic cells of different cell lineages in organotypic microcultures. Recombinant human hematopoietic growth factors interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF) significantly stimulated the endogenous cell production of some but not all of the individually treated Hematons, indicating the heterogeneity of factor-responsive cells within the Hematon population. Comparative observations of 184 BM aspirates support the hypothesis that the presence of Hematons in a BM aspirate correlates positively with homeostatic blood cell production, because the Hematon was present in normal BM (31/40) and it was rare among patients with myelodysplastic syndromes (15/53), acute myeloblastic leukemia (7/39), and chronic myelocytic leukemia (5/52). We suggest that the Hematon represents a unifying model around which the variability of fundamental BM functions and dysfunctions can be explored.

Bone Marrow↗
PubMed1987

Socioeconomic conditions, food habits and formulated food programs in the Pueblos Jóvenes of Lima, Peru.

The present article examines attempts to develop and introduce formulated foods, or mixes, to low-income populations in Lima, Peru's Pueblos Jóvenes (squatter settlements). It discusses how socioeconomic conditions, dietary patterns, and economic pressures often mitigate against consumer acceptance. An alternative approach which stresses a prediagnostic study of clients' needs and careful monitoring of product development with consumer input is suggested.

Adolescent↗
PubMed1987

Treatment of advanced colorectal and gastric adenocarcinomas with 5-fluorouracil and high-dose folinic acid.

We report the results of an expanded trial of 5-fluorouracil (FUra) combined with high-dose folinic acid for treatment of patients with advanced colorectal or gastric adenocarcinoma. In each treatment course, the patients received both FUra (340-400 mg/m2/day by iv infusion over 15 minutes) and folinic acid (200 mg/m2/day by iv bolus) for 5 consecutive days, with a 21-day interval between courses. Eighty-six patients with colorectal carcinoma were evaluated. The combined complete response (CR) and partial response (PR) rates were 39% for 54 patients who did not receive prior chemotherapy and 22% for 32 patients who had previously received chemotherapy. Four patients who were previously resistant to FUra attained objective responses. The median time to disease progression for the 28 responders was 10 months. The median survival time of responders was 19.5 months, and the probability of their being alive at 2 years was 40%. Of 27 patients with gastric adenocarcinoma, 13 (48%) responded to therapy. Their median time to disease progression was 5.5 months. The median survival time of responders was 11 months, and their probability of being alive at 15 months was 30%. Toxicity was within acceptable limits. Toxic effects included stomatitis, diarrhea, conjunctivitis, skin rash, and mild myeloid hypoplasia. In a separate study, plasma concentrations of L-folates above 10(-5) M were achieved after a rapid single iv injection of 200 mg/m2 of folinic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1987

[Therapeutic trials of aclarubicin in previously treated acute leukemias and hematosarcomas].

In a phase I-II trial, 38 patients with acute myeloid leukemia (AML) were given single drug induction therapy with aclarubicin (ACM) according to two dosing schedules: treatment 1: 10 to 30 mg/m2/d to a maximum total dose of 300 mg/m2 or until development of unacceptable toxicity: treatment 2: 15 mg/m2/d in ten-day courses separated by ten-day intervals. Response rates were 15% with treatment 1 and 44% with treatment 2 (overall response rate 34%). Complete remission (CR) was achieved in 6 patients who had previously failed to respond to adriamycin (ADM). Toxicity was more frequent and more severe in those patients given more than 150 mg/m2 ACM per course. The main side effects were oropharyngeal mucositis and diarrhea. Three patients exhibited T wave inversion and one had an episode of auricular flutter. In a separate trial in 16 patients with AML we used cyclic chemotherapy combining ACM (20 mg/m2/d) and ARA-C (200 mg/m2/d) for seven consecutive days. Complete remission rate was 50%. Severe ventricular rhythm disorders were seen in two patients. In a phase I-II study, 19 patients with acute lymphoid leukemia (ALL) and 8 patients with non-Hodgkin lymphoma (NHL) were given ACM alone according to the regimen designated treatment 1 described above. Response rates were 11% (2/19) in ALL and 25% (2/8) in NHL. A review of the literature is presented in the discussion of the original trials reported herein.

Aclarubicin↗
PubMed1986

Excess of lympho-reticular cell complexes in the bone marrow linked to T cell mediated dysmyelopoiesis.

The term dysmyelopoietic syndrome (DMPS) covers a variety of closely related disorders with various etiological factors, and characterized by chronic (pan) cytopenias whose prognosis and treatment are still controversial. Despite the recent efforts to identify pathogens, effector cells and soluble cell products involved in the development of this syndrome only a few comprehensive experimental data are available, useful for elaboration of therapeutic regimens. We describe here a patient with DMPS who was refractory to inductive chemotherapy. Initial agar gel culture studies revealed the activity of hematopoiesis inhibitory T cells within the bone marrow that could be suppressed by prednisone both in vitro and in vivo. However another pathological cell features, the excess of an unusual lympho-reticular cell complexes was identified in long-term liquid cultures. These symbiotic cell complexes persisted throughout the disease, despite the prednisone induced hematological remission, suggesting their causative role in the disease, that more recently progressed towards acute myeloid leukemia.

Adult↗