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Biomedical subjects

L Catalano

Publications and source records attributed to L Catalano.

At least 19 recordsLinked to original sources

Delta-CHr improves the identification of anemic syndromes and the evaluation of hemoglobin synthesis.

Reticulocyte hemoglobin content (CHr) is considered an index of iron status, helpful in the differential diagnosis of microcytoses. Its potential can be enhanced by comparing CHr dynamic reference values (CHr-e: expected CHr), which are proportional to the MCVr variations occurring in micro- or macrocytosis, with measured CHr values. We demonstrate that the difference between measured CHr and CHr-e (DeltaCHr) is helpful to differentiate the anemic syndromes and, in particular, beta-thalassemia vs. presumable sideropenia. DeltaCHr can also indicate when to interrupt iron supplementation. DeltaCHr allows an insight into the erythropoiesis of thalassemic and sideropenic subjects, pointing out the reduced hemoglobin production and ineffective erythroid activity in these conditions.

Anemia, Iron-Deficiency↗

Washout of [99mTc] sestamibi in predicting response to chemotherapy in patients with multiple myeloma.

AIM: Technetium-99m 2-methoxy-isobutyl-isonitrile ([99mTc] MIBI) has been successfully used to study patients with multiple myeloma (MM). This tracer is also a substrate for P-glycoprotein (Pgp). Since Pgp overexpression is one of the primary mechanisms of multidrug resistance in MM, the aim of this study was to test whether [99mTc] MIBI could be an index of Pgp overexpression and function in MM and therefore predicts response to chemotherapy. METHODS: Forty patients with MM (12 in stage I, 15 in stage II, and 13 in stage III) showing diffuse bone marrow [99mTc] MIBI uptake were included in the study. All patients underwent whole body scintigraphy at 10 and 60 minutes after i.v. injection of 555 MBq of [99mTc] MIBI. [99mTc] MIBI washout was measured, after decay correction, as: (10 minute counts/pixel minus 60 minute counts/pixel) divided by 10 minute counts/pixel, computed on a region of interest drawn on the thoracic spine (posterior projection), taking care of avoiding heart and splanchnic organs. Disease restaging was performed at a mean time of 32+/-20 months, and patients were considered to be in remission (complete or partial) or to show disease progression on the basis of a complete clinical and hematological evaluation. RESULTS: Patients showing disease progression at restaging (n=26) had higher washout (19.3+/-9.8% vs 12.8+/-6.9%, p<0.05) than patients in remission (n=14). Disease free survival was significantly better in patients with lower washout of [99mTc] MIBI. No differences in therapeutic regimen and stage of disease at admission were found between the 2 groups. When patients treated with melphalan were excluded from the analysis, 87.5% of patients in remission had low washout. CONCLUSIONS: The present study suggests a potential role of [99mTc] MIBI washout in predicting response to chemotherapy in patients with MM.

Antineoplastic Agents↗

Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma.

In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively 99mTc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with 99mTc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent 99mTc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of 99mTc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of 99mTc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P<0.0001) and in vivo score (Spearman rank correlation coefficient r=0.60, P<0.01). No specific tracer uptake was found in bone marrow samples obtained from the two healthy donors. Micro-autoradiography showed localization of 99mTc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner compartments.

Aged↗

Predictive value of technetium-99m sestamibi in patients with multiple myeloma and potential role in the follow-up.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI or setamibi) has recently been proposed for use in the evaluation of multiple myeloma (MM). The aims of this study were to investigate its potential predictive value in patients with MM and its possible role in the follow-up. Thirty patients with MM who had undergone two 99mTc-MIBI scintigraphic studies at least 2 months apart constituted the study group; 22 of them received chemotherapy in the interval between the two scans. The scans were classified as showing pattern N when only physiological uptake was present, pattern D when diffuse bone marrow uptake was observed, pattern F when areas of focal uptake of the tracer were evident, and pattern F + D when both D and F patterns were observed. Comparative 99mTc-MIBI scintigraphy was considered indicative of disease progression when there was a worsening of the pattern (i.e. from N to D, or from N or D to F or to F + D) or an increase in the pattern D semiquantitative score. It was considered indicative of disease improvement when the opposite trend was observed; otherwise, it was considered to document a stable condition. A significant association was observed between the baseline scintigraphic pattern and clinical status at follow-up in the group of patients evaluated after chemotherapy (chi 2 = 16.7, P < 0.05). A negative baseline 99mTc-MIBI scintigram showed a high predictive accuracy (100%) for remission, while the presence of pattern F or F + D was often associated with a less favourable outcome. A multivariate analysis showed that 99mTc-MIBI uptake pattern has an added value in relation to known prognostic variables such as C-reactive protein. 99mTc-MIBI scintigraphy patterns at follow-up were significantly associated with the clinical status evaluated after chemotherapy (chi 2 = 32.6, P < 0.0001). Considering pattern N as indicating remission, pattern D stable condition, and pattern F or F + D progressive disease, a high concordance between scintigraphic findings and clinical status was found in the 22 patients undergoing chemotherapy (91%). Variation in 99mTc-MIBI findings comparing baseline and follow-up evaluations was significantly associated with clinical status both in patients undergoing chemotherapy (chi 2 = 26.5, P < 0.0005) and in those not undergoing chemotherapy (chi 2 = 8.0, P < 0.005). In conclusion, the results of this study suggest a prognostic value of 99mTc-MIBI scintigraphy in patients with MM and a potential role during the follow-up.

Aged↗

Prolonged response to cyclosporin-A in hypoplastic refractory anemia and correlation with in vitro studies.

BACKGROUND AND OBJECTIVE: Lymphocyte abnormalities in myelodysplastic syndromes (MDS) have been widely described, but the role of the immune system in the pathogenesis of these clonal disorders remains controversial. An active role of lymphocytes in suppressing normal hematopoiesis may be implicated in MDS with hypoplastic marrow. We have studied in vitro and in vivo activity of cyclosporin-A (CSA) on hematopoiesis in patients affected by hypoplastic MDS without blast excess. DESIGN AND METHODS: Nine consecutive patients with hypoplastic refractory anemia (RA), followed up in our out-patient unit, were treated with CSA at daily doses of 1-3 mg/kg for at least three months. Low dose steroids or danazol were transiently added in 7/9 patients. Differences between pre- and post-treatment parameters were studied by the Student's t-test. In vitro effect of CSA on circulating hematopoietic progenitors was studied by the methylcellulose colony assay. RESULTS: Before treatment, fewer circulating hematopoietic progenitors were found in all patients as compared to normal subjects. The number of CD34+ cells was about halved, while circulating erythroid and myeloid colony-forming cells (CFC) were reduced to one-fifth. After a mean period of 22 months of CSA treatment (median: 14.5 months), hemoglobin was significantly and persistently increased in two patients, platelets in one, platelets and hemoglobin in two. Two patients showed transient responses, one patient did not tolerate the treatment and one patient is close to a significant response. At in vitro CSA concentrations similar to those achieved in vivo after oral administration the drug significantly increased cell colony growth in hypoplastic RA. This test correctly predicted a positive clinical response to CSA in 3/5 cases and treatment failure in 4/4 cases. INTERPRETATION AND CONCLUSIONS: About one half of hypoplastic RA patients benefited from CSA treatment. A larger study could verify whether in vitro culture of hematopoietic progenitors in the presence of CSA can predict the clinical response and whether this treatment could prolong patients' survival.

Adult↗

Tc-99m sestamibi scintigraphy in multiple myeloma.

Tc-99m sestamibi imaging was performed in two patients with multiple myeloma. Focal areas of increased uptake in one patient and diffuse skeletal uptake in the second patient were found. Tc-99m sestamibi appears to identify bone marrow and osteolytic involvement in multiple myeloma.

Adult↗

Detection of focal myeloma lesions by technetium-99m-sestaMIBI scintigraphy.

BACKGROUND AND OBJECTIVE: The tracer tachnetium-99m-2-methoxy-isobutyl-isonitrile (Tc99m-sestaMIBI) has recently been shown to concentrate in some neoplastic tissues, including myeloma. We investigated the diagnostic capacity and limits of this procedure in tracing focal myeloma lesions, and compared them with those of conventional radiological procedures (Xr). DESIGN AND METHODS: We studied 55 patients suffering from multiple myeloma (MM) or solitary plasmacytoma in different stages and clinical conditions, or from monoclonal gammopathy of undefined significance (MGUS), by whole body scans obtained 10 minutes after injection of 555 MBq of Tc99m-sestaMIBI. Scans were defined as normal (physiological uptake only), diffuse (presence of bone marrow uptake), or focal (localized areas of uptake), and were compared to conventional skeletal Xr. RESULTS: Thirty patients showed no focal areas of Tc99m-sestaMIBI uptake; this group consisted of 5 patients with MGUS, 6 with MM in stage IA and 2 in stage IIA, 11 patients studied after effective chemotherapy and 6 in early relapse. Twenty-five patients showed one or more spots of focal uptake: all of them had active disease (untreated, resistant or relapsing MM). In the setting of tracing focal lesions, Tc99m-sestaMIBI scans were concordant with the radiological examination in 38 patients and discordant in 17. Among the latter, in 4 cases Tc99m-sestaMIBI revealed focal lesions not detected by Xr, and in 13 cases lytic areas detected by Xr did not show Tc99m-sestaMIBI uptake. INTERPRETATION AND CONCLUSIONS: In untreated patients, the number of lesions revealed by Tc99m-sestaMIBI was comparable to that shown by Xr, while in pretreated patients Tc99m-sestaMIBI traced a number of lesions lower than that detected by Xr. The reason for this discrepancy is that Tc99m-sestaMIBI traces only active lesions. Tc99m-sestaMIBI limitations in identifying focal lesions may derive from the dimension of the smallest traceable lesion (about one centimeter), and from the possibility that focal plasma cell localizations in collapsed bone may not be visualized due to inadequate vascularization. Tc99m-sestaMIBI scintigraphy is an interesting tool for diagnosing, staging and following up focal myeloma lesions, in the bone as well as in soft tissues. It is more specific than conventional Xr in identifying sites of active disease.

Adult↗

Early detection by ultrasound scan of severe post-chemotherapy gut complications in patients with acute leukemia.

BACKGROUND AND OBJECTIVE: Acute leukemia patients may develop life-threatening gut complications after intensive chemotherapy. We evaluated the role of abdominal and pelvic ultrasound (US) examination in early detection of these complications. DESIGN AND METHODS: A cohort of twenty adult acute leukemia patients undergoing intensive chemotherapy for remission induction entered the study. All chemotherapy regimens included cytarabine by continuous i.v. infusion for several days. RESULTS: Three patients had severe gut complications: 2 cases of enterocolitis and 1 case of gall bladder overdistension in the absence of calculi. In all cases the abnormality was documented by US examination: US scan showed thickening of the intestinal wall (two cases), and gall bladder overdistension with biliary sludge (one case). Immediate medical care included bowel rest, a broad-spectrum antibiotic, antimycotic treatment, and granulocyte colony-stimulating factor. All patients recovered from the complication. INTERPRETATION AND CONCLUSIONS: We believe that the favorable outcome obtained in our small series can be attributed to early diagnosis followed by appropriate treatment. Early recognition by US and immediate medical management can lead to complete recovery of severe intestinal complications in patients with acute leukemia undergoing intensive chemotherapy.

Acute Disease↗

AlphaIFN-induced hematologic and cytogenetic remission in chronic eosinophilic leukemia with t(1;5).

Chronic eosinophilic leukemia (CEL) is a myeloproliferative disease characterized by excessive eosinophilic proliferation with clonal cytogenetic abnormalities. The most frequent cytogenetic abnormality is a break in the q 31-35 region of chromosome 5, where genes encoding for IL-3, IL-5 and GM-CSF (all cytokines involved in eosinophilopoiesis) are located. We report the case of a patient with CEL with t(1;5) (q23;q31), who obtained complete hematologic and major cytogenetic response after two years of alpha-interferon (alpha-IFN) therapy. Two other cases of complete response to alpha-IFN are reported in the literature. A trial with alpha-IFN could be considered as front line treatment in this rare disease.

Adult↗

Different patterns of technetium-99m sestamibi uptake in multiple myeloma.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI) has been proposed as a potential tracer in patients with multiple myeloma (MM). The aims of this study were to evaluate the incidence of various patterns of diffuse 99mTc-MIBI uptake in patients with MM, to assess their relationship with clinical status and stage of disease, and to try to clarify the meaning of the diffuse bone marrow uptake of 99mTc-MIBI. Thirty-nine consecutive patients with MM were studied. Twenty-nine of these patients had active disease (13 in stage I, ten in stage II, and six in stage III) and ten were in remission after chemotherapy. Anterior and posterior whole-body scans were obtained 10 min after i.v. injection of 555 MBq of 99mTc-MIBI. The scans were classified as showing: pattern N, when only physiological uptake was present; pattern D, when diffuse bone marrow uptake was observed; pattern F, when areas of focal uptake of the radiotracer were evident; or pattern D+F, when both D and F patterns were observed. Diffuse bone marrow uptake was scored according to extension and intensity. Seven of the 39 patients (18%) showed pattern N, 18 (46%) pattern D, 2 (5%) pattern F, and 12 (31%) pattern D+F. Of the 32 patients with a positive 99mTc-MIBI scan (i.e. showing pattern D, F or D+F), 29 (91%) had active disease. Only three patients in remission showed pattern D, but with a very low bone marrow uptake score. Both extension and intensity of diffuse bone marrow uptake correlated with the amount of the monoclonal component and the percentage of bone marrow plasma cells. The distribution of the 99mTc-MIBI uptake patterns differed among patients in different stages of disease. Using as criteria for advanced stage the presence of either focal uptake (pattern F or D+F) or pattern D with a high score, high (90%) diagnostic accuracy was obtained. In conclusion, the patterns of 99mTc-MIBI uptake in patients with MM are related to both the clinical status and the stage of disease. The presence of focal uptake or of intense diffuse bone marrow uptake suggests that the patient has active and advanced stage disease, while a negative scan in a patient with MM clearly indicates remission.

Antibodies, Monoclonal↗

All-trans-retinoic acid (ATRA) responsive skin relapses of acute promyelocytic leukaemia followed by ATRA-induced pseudotumour cerebri.

A 30-year-old woman with acute promyelocytic leukaemia (APL) went into complete remission following idarubicin and cytarabine chemotherapy; 18 months later she developed repeated skin relapse, with no bone marrow involvement. DNA and RNA analysis of skin lesions revealed the presence of the PML/RAR alpha hybrid gene, which was not detected at the same time in bone marrow. The skin relapses were successfully treated by all-trans-retinoic acid (ATRA) as single agent over 2 years. However, prolonged administration of ATRA caused pseudotumour cerebri, which disappeared upon drug withdrawal. The absence of the hybrid gene in the bone marrow by RT-PCR analysis led to the patient being autografted.

Adult↗

Trisomy 13 in a patient with leukemic progression of myelodysplasia.

Four months after the diagnosis of refractory anemia, a 60-year-old patient developed acute leukemia with blast cells that were poorly differentiated by morphology and clearly myeloid by immunophenotyping. Cytogenetic analysis performed at leukemization showed trisomy 13. An extra copy of chromosome 13 has already been reported in a few cases of acute leukemia and myelodysplastic syndrome.

Anemia, Refractory↗