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Biomedical subjects

C Castagnola

Publications and source records attributed to C Castagnola.

At least 19 recordsLinked to original sources

Efficacy, toxicity and feasibility of a shorter schedule of DCEP regimen for stem cell mobilization in multiple myeloma.

From 2000 to 2004, 152 patients with multiple myeloma aged or=4 x 10(6) cells/kg. The proportion of patients in whom mobilization failed was similar in the two groups. The incidence of WHO grade III neutropenia was higher in group II, although the difference was not statistically significant; the percentage of patients requiring hospitalization for severe infections was similar in the two groups. The incidence of WHO grade IV thrombocytopenia did not differ between the two groups. The response rate was 72% in group I and 80% in group II with similar percentages of patients achieving good responses. DCEP-short is a good mobilizing regimen, sharing the same characteristics as infusional-DCEP: high mobilizing efficacy, low toxicity and good antitumor activity. This new schedule of DCEP does, however, allow complete outpatient management and so could be advantageously included in any high-dose therapy program.

Antigens, CD34↗

Successful therapy with high-dose steroids and cyclosporine for the treatment of carmustine-mediated lung injury.

The treatment of the pulmonary toxicity induced by carmustine is nowadays based on the use of corticosteroids that generally lead to a rapid resolution of pneumonitis. On the contrary, no therapeutic alternatives are reported for those patients who do not respond to steroids. We describe a case of non-Hodgkin's lymphoma in a patient who developed a severe interstitial pneumonitis after an autologous transplantation including carmustine in the conditioning regimen. He was successfully treated with an association of steroids and cyclosporine A with a rapid improvement of symptoms and a complete resolution of pneumonitis. This is, to our knowledge, the first case of carmustine-induced pneumonitis, resistant to steroids alone, successfully treated with cyclosporine A. This suggests an immunoallergic mechanism in the pathogenesis of the damage, which can be reversed with prompt therapy.

Adult↗

Consolidation treatment with autologous peripheral blood progenitor cell transplantation in acute myeloid leukemia: a single center experience.

Several trials have suggested that intensive post-remission therapy may prolong the duration of complete remission (CR) in acute myeloid leukemia (AML). The purpose of this study was to evaluate the feasibility and the efficacy of high-dose cytarabine (HiDAC) consolidation chemotherapy followed by high-dose therapy and autologous infusion of peripheral blood progenitor cells (PBPC) mobilized by G-CSF in adult patients with AML in first CR. Fifteen consecutive AML patients underwent HiDAC consolidation chemotherapy, used as a method of in vivo purging, followed by G-CSF for the purpose of autologous PBPC collection. Eleven patients collected a median of 6.9x10(8)/kg peripheral blood mononuclear cells (MNC) (range 2.9-23) and a median of 6.67x10(6)/kg CD34+ cells (range 1.8-33.5) with a median of two aphereses (range 1-3). Two patients did not mobilize and two obtained an inadequate number of progenitor cells. The 11 patients with adequate collections received myeloablative chemotherapy followed by the infusion of PBPC. The median number of days to recover neutrophils and platelets was 12 and 13, respectively. After a median follow-up of 28.7 months (range 17.2-43.4), five out of 11 patients who underwent PBPC transplantation are still in CR, five have died in first relapse and one is alive in CR after relapse treated with salvage therapy and second PBPC infusion. These results demonstrate that HiDAC consolidation chemotherapy followed by autologous PBPC transplantation is a feasible procedure with minimal toxicity. Randomized studies should be performed to evaluate whether this form of consolidation may produce a significant improvement in leukemia-free survival.

Acute Disease↗

Trisomy 11 and a complex t(11;11;22) in a patient with acute myelomonocytic leukemia (AML-M4) following myelodysplasia (MDS): a cytogenetic study of a mechanism of leukemogenesis.

We describe a 73-year-old man diagnosed with acute myelomonocytic leukemia (AML-M4) following myelodysplasia with trisomy 11 and with a t(11;11;22). This is the first case with both abnormalities present in the same cells and with the t(11;11;22) involving a chromosome 11 already duplicated at 11q23. This band contains the MLL gene that undergoes partial tandem duplication in patients with +11, which is "promiscuous," being translocated with a large number of genetic partners. Our patient had a complex karyotype that was completely defined by in situ hybridization. This technique demonstrated that the t(11;11;22) derivative with a duplication of band 11q23 carried from three to four copies of MLL. Two copies of the gene were close to each other and centromeric to the break-point region. Therefore, a partial tandem duplication of the MLL gene might have happened before the occurrence of t(11;11;22). Considering the associated chromosome defects, the monosomy for the long arm of chromosome 7, due to an unbalanced translocation t(7;17), further underlines the possibility that a partial tandem duplication of the MLL gene might have taken place.

Aged↗

Assessment of renal function in patients with multiple myeloma: the role of urinary proteins.

Renal failure (RF) in multiple myeloma (MM) is considered an ominous complication even though, when timely therapy is started in patients with minimal damage, a high percentage of cases can achieve a regression. The evaluation of renal involvement usually relies on serum creatinine or its clearance, but these parameters have proved to be inadequate to identify initial damage. The aim of this study was to assess the role of the following urinary proteins in diagnosing renal impairment at an early stage: high-molecular-mass proteins (transferrin, IgG, albumin) as markers of glomerular damage, and low-molecular-weight proteins and parenchymal enzymes [alpha(1)-acid glycoprotein (AGP), alpha(1)-microglobulin (alpha(1)M), retinol-binding protein (RBP), beta(2)-microglobulin (beta(2)M), lysozyme (LZ), and N-acetyl-beta-d-glucosaminidase (NAG)] as indicators of tubular disorder. Thirty MM patients (nine at disease onset and 21 previously treated) were included in the study. No correlation was found between the urinary proteins and the phase or the stage of the disease. By the Spearman test, Bence Jones proteinuria correlated significantly with the 24 h proteinuria (p=0. 01) and beta(2)M (p=0.02), and weakly with the alpha(1)M. Serum creatinine concentrations and urea correlated with most of the analytes evaluated: RBP correlated well with urea (p=0.004) and creatinine (p=0.004); IgG (p=0.006) albumin (p=0.009), AGP (p=0.04), and NAG (p=0.02) correlated with serum creatinine. Significant statistical correlation was found between all the analytes except LZ and the creatinine clearance. Twelve of the 30 MM patients (40%) showed abnormal values of urinary proteins. Four of these patients showed overt renal failure with significant modification of the serum parameters and of creatinine clearance, three showed an isolated decrease of creatinine clearance, and five did not present any alteration of serum or urinary parameters. This testifies to the utility of urinary proteins in highlighting renal damage even in cases where the customary serum indicators of renal disorder are normal. In conclusion, our results demonstrate that AGP, RBP, NAG, transferrin, and IgG are good indicators of renal damage. They do not correlate with the severity of the disease, but they seem to be helpful in identifying a subset of patients with initial renal dysfunction.

Adult↗

Acute lymphoblastic leukaemia occurring as second malignancy: report of the GIMEMA archive of adult acute leukaemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.

Between July 1992 and June 1996, 901 new cases of adult acute lymphoblastic leukaemia were recorded in the GIMEMA Archive of Adult Acute Leukaemia; 21 of them (2.3%) had a previous primary malignancy (PM). We found that secondary acute lymphoblastic leukaemia cases (sALL) presented with older age, a high incidence of pre-pre-B immunophenotype and a significantly higher prevalence of cancer among relatives compared to de novo ALL. The leukaemogenic activity of the cytotoxic drugs employed for the treatment of PM may have played a potential role in only a proportion of patients, opening the possibility that some sALL patients may have developed two or more malignancies due to individual predisposing factors.

Adolescent↗

A complex translocation (5;7) in a patient with acute nonlymphocytic leukemia evolved from a myelodysplastic syndrome.

Complete or partial monosomy for the long arms of chromosomes 5 or 7 or both is frequently observed in therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia. Sporadic cases have been reported in which partial monosomy is due to unbalanced translocations. The patient described herein carries one such rearrangement. 46,XY,t(1;2) (q32;p23),del(5)(q13),der(7)(5qter-->5q22::7p15-->7 q21:),del(12)(p12), resulting in partial monosomy for the long arms of chromosomes 5 and 7 and in partial monosomy for the short arm of chromosome 7.

Chromosome Deletion↗

Randomized clinical study comparing aggressive chemotherapy with or without G-CSF support for high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia evolving from MDS.

One hundred and five consecutive primary high-risk myelodysplastic syndromes (MDS) or secondary acute myeloid leukaemia (sAML) evolving from MDS (performance status 0-3, ECOG) entered this study. Induction chemotherapy (CT) consisted of idarubicine 12 mg/m2 i.v. on days 1 and 2, etoposide 60 mg/m2/12h i.v. for 5d, Ara-C 120 mg/ m2/12h i.v. for 5d (one or two courses). Patients were randomized to receive or not G-CSF (5 microg/kg/d subcutaneously 48 h after the end of CT). 52 cases underwent CT alone and 53 CT+G-CSF. The CT+ G-CSF patients had a significantly shorter duration of neutropenia (8 nu 16d) with a lower incidence of infections and significantly better responses (CR+PR: 74% v 52%, P<0.05). 40 patients entered CR: 17 with CT and 2 3 with CT+G-CSF. Responders underwent two consolidation courses with the same CT, followed by high-dose Ara-C (2 g/m2 every 12h for 3 d). Most CRs were clonal. At present 21 responders have relapsed (median relapse-free survival 4 5 months). Eight responders received an allo-BMT, six are alive in CR 7-57 months post-transplant. Therefore allo-BMT only increases the chance of a long survival and possible cure. In conclusion, CT+G-CSF did not prolong either CR duration or survival; the growth factor support, however, increased the number of allo-transplantable cases by inducing higher remission rates and improving clinical conditions.

Acute Disease↗

[Can the prostatic capsule be preserved during cystectomy for bladder tumors: a study of urethral and prostatic involvement in the cystectomy specimens].

OBJECTIVES: To evaluate the frequency of urethral and prostatic lesions on cystectomy specimens for bladder tumour. MATERIAL AND METHODS: This retrospective histological study was based on 260 specimens: radical cystectomies performed in 7 operative sites. The prostate and urethra were analysed in 3 planes (upper, middle and lower thirds). The apex was studied separately. Urethral invasion was identified by continuity of the tumour or by the presence of vesical CIS. RESULTS: Urethral involvement is frequent (30.6% cases) essentially due to contiguous invasion (43/80). CIS is the second pathological association (44 urethral CIS/75 bladder CIS). Prostatic adenocarcinoma was present in 17.8% of cases with a Gleason score > 6 for 30% of lesions. CONCLUSION: The high frequency of urethral and prostatic involvement does not justify preservation of the prostate during cystectomy. A serial prospective study should define the precise criteria able to minimize the risk of conservative surgery.

Adenocarcinoma↗

Efficacy of a combination of idarubicin, etoposide and intermediate-dose cytosine arabinoside as salvage therapy in relapsing or resistant unfavorable lymphoma.

BACKGROUND AND OBJECTIVE: Idarubicin, an anthracycline analogue, is active in non-Hodgkin's lymphoma. This study evaluates the efficacy and toxicity of a combination of idarubicin, etoposide and intermediate-dose cytarabine (IVA) in unfavorable lymphoma in relapse or resistant to prior doxorubicin- or novantrone-based regimens. DESIGN AND METHODS: Thirty patients with relapsing or resistant unfavorable lymphoma received a combination of idarubicin 12 mg/m2 i.v. on day 1, etoposide 60 mg/m2 i.v. every 12 hours for 3 days, and Ara-C 1 g/m2 i.v. every 12 hours for 3 days (3-hour infusion). Median age was 39 years (range: 22-60). All patients had been given prior doxorubicin or novantrone; 54% of them had received 2 or more chemotherapy regimens; 67% of total were in clinical relapse (30% in their second relapse), and 23% had resistant disease. RESULTS: The overall response rate to IVA was 60% (18 of 30 patients). Complete remission rate was 20% (6 of 30) in the whole group, 45% (5 of 11) among patients in their first relapse. Remission median duration was 9 months (range: 1-18), with a 3-year relapse-free and overall survival of 20% and 15%, respectively. Severe neutropenia occurred in 13 patients (43%) and severe thrombocytopenia in 11 patients (37%), with a median duration of 9 and 13 days, respectively. No cardiac toxicity developed; sepsis during neutropenia was documented in four instances and two patients (7%) died of therapy-related events (septic shock). INTERPRETATION AND CONCLUSIONS: Idarubicin combined with etoposide and intermediate-dose cytarabine proved to be an active salvage therapy in unfavorable lymphoma given prior doxorubicin or novantrone; the best results were obtained among patients in their first relapse, with low tumor burden.

Adult↗

Management of acute promyelocytic leukemia relapse in the ATRA era.

BACKGROUND AND OBJECTIVE: The use of all-trans retinoic acid (ATRA) has changed the natural course of acute promyelocytic leukemia (APL), increasing the percentage of lasting complete remissions. However, management of the few relapses remains undefined. The purpose of the present study was to evaluate the different behavior of APL patients relapsed after induction chemotherapy which had or had not included ATRA. DESIGN AND METHODS: We retrospectively studied 8 patients (3 male and 5 female) who had relapsed after a clinical and molecular complete remission (CR). Five patients relapsed after conventional chemotherapy including anthracyclines, without ATRA which was not available at the onset (group A), 3 relapsed after induction treatment according to AIDA protocol (Idarubicin + ATRA) (group B). Seven patients had both molecular and clinical relapses, 1 (group B) had only a molecular relapse. The median first CR duration was 33 months (range 8-63). To induce a second CR all patients were treated with ATRA 45 mg/m2/day given orally until CR, combined with mitoxantrone 6 mg/m2/day for 6 days and cytarabine 1 g/m2/day for 6 days. RESULTS: Seven out of 8 patients (87.5%) achieved second CR, 1 (group A) did not respond and died within two months. Second CR duration was 21, 43+, 56+, 62+ months in group A and 5, 10, 12+ (with molecular relapse) months in group B. Therefore, only one patient relapsed in group A, while all the group B patients relapsed. INTERPRETATION AND CONCLUSIONS: ATRA combined with chemotherapy is an effective approach to treating APL relapse. It produces a high incidence of second CR with an acceptable toxicity. The duration of the second CR seems, however, to be longer in patients never treated with ATRA before than in patients who relapsed after the AIDA protocol. Therefore, it might be appropriate to adopt more aggressive protocols in this latter subset of patients.

Adolescent↗

Thrombotic events are not exclusive to the remission induction period in patients with acute lymphoblastic leukemia: a report of two cases of cerebral sinus thrombosis.

It is well established that in acute lymphoblastic leukemia (ALL) patients L-asparaginase (L-Ase) provokes thrombotic events reducing coagulation inhibitors in both adults and children. A tight correlation between thrombotic and hemorrhagic complications and ALL has also been hypothesized because of the high incidence of disseminated intravascular coagulation (DIC) found during the early period of chemotherapeutic treatment apart from L-Ase. All the authors reporting on this subject, however, consider the remission induction phase of treatment the most risky, if not exclusive, for the development of a thrombotic event, in particular if it includes the administration of L-Ase. We report here two cases of ALL patients who experienced a cerebral sinus thrombosis in a later phase of treatment, demonstrating that the thrombotic risk is surely exacerbated by chemotherapy but is not exclusive to the remission induction period.

Adult↗

Growth factors in the therapy of myelodysplasia: biological aspects.

Growth factors (GF) are reported to play an important role in the therapy of myelodisplastic syndromes (MDS). After in vitro administration a consistent group of MDS may respond to GF but the possibility of differentiation, regulation or expansion of myelodisplastic clones following GF therapy is still a question to be answered as their optimum dose and combinations. To validate if in vivo treatment with GF, may promote the regulation or the recovery of myelopoiesis and/or modify the clonality of the responses, we gave G-CSF after intensive chemotherapy in high risk MDS and acute leukemia evolving from MDS patients. According to our data the use of G-CSF after intensive chemotherapy may improve the CR rate without increase of leukemic transformation. However the answer were clonal and the remission duration remained very short so we suggest to utilize this time to perform other therapeutic strategies such as, when possible, the BMT.

Adult↗

[Contribution of computed tomography in the staging of upper urinary tract urothelial tumors. Importance of the tumor diameter measurement].

OBJECTIVES: To demonstrate a correlation between abdominal computed tomography (CT) data and the histological stage of upper urinary tract tumour (UUTT) in order to more accurately define therapeutic indications. MATERIALS AND METHODS: From 1984 to 1995, 51 patients were treated for UUTT and were assessed by preoperative abdominal CT. 41 of the 51 CT scans were considered to be interpretable and were reviewed retrospectively by a single radiologist. The CT stage and tumour diameter were compared to the pathological stage. RESULTS: CT staging had a reliability of 76%, by combining stages Ta-T2, which could not be distinguished. The sensitivity of CT to assess invasion of the renal parenchyma and ureteric or perirenal fat was 100% and 70%, respectively, with a specificity of 82% and 97%. The accuracy can be improved by decreasing the thickness of sections of the tumour. Tumour diameters (d) of pyelocaliceal tumours, measured by CT and pathology, were closely correlated (r2 = 0.83). All UUTTs less than 3 cm in diameter were found to be superficial on histology. CT correctly estimated the size of these small tumours in 14/15 cases. Overall, by setting the limit at 3 cm, CT was able to detect a superficial pyelocaliceal tumour with a specificity of 92% and a PPV of 93%; however, a CT size > or = 3 cm is not predictive of the histological stage of the lesion. CONCLUSIONS: CT is still imprecise for the staging of UUTT, as it cannot distinguish between Ta, T1 and T2 lesions, and is still not sufficiently reliable in the assessment of invasion of the periurothelial fat or of the renal parenchyma. CT measurement of the diameter of pyelocaliceal tumours can provide an argument in favour of the superficial nature of the lesion and therefore guide the therapeutic decision towards a conservative approach.

Adult↗

[Tendinopathy and fluoroquinolones].

Tendinopathies, essentially involving the Achilles tendon, which tendon rupture, can be secondary to treatment with fluoroquinolones, and facilitated by corticosteroid therapy, renal failure and sport. Fluoroquinolone treatment must therefore be prescribed cautiously and patients must be advised to stop treatment at the slightest warning signs of tendinitis.

Achilles Tendon↗

[Quality of life and skin urinary diversions. Results of a questionnaire completed by 73 patients].

UNLABELLED: The objective of this study was to evaluate the quality of life of patients with a cutaneous urinary diversion. MATERIAL AND METHODS: A 25-item self-administered questionnaire was sent to 73 patients with a cutaneous urinary diversion, either non-continent (NCD), such as a transileal cutaneous ureterostomy, or continent (CD), such as a Mainz or Kock reservoir. RESULTS: 66 patients answered the questionnaire: 34 NCD and 32 CD. The mean follow-up was 69.2 years for NCD and 58 years for CD. No significant difference was demonstrated between the two samples in terms of the interference of their diversion with their everyday life. Most patients declared that their sex life was now "severely disturbed". However, 3 patients regained a sexual activity after their diversion. Patients with an ideal conduit presented a higher incidence of stoma problems. Overall, 90% of patients with an NCD and 97% of those with a CD were satisfied or very satisfied with their diversion. CONCLUSION: Regardless of the type of diversion, patients were satisfied with their operation. When a cutaneous diversion is necessary, the choice of a continent or non-continent diversion cannot be solely based on the argument of "continence". The best possible choice, as a function of surgical limitations and the patient's desires, can only be determined on the basis of a dialogue between the surgeon and the patient.

Dermatologic Surgical Procedures↗