Atypical APL including multiple translocations and abnormal response to micronuclei induction test.
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Biomedical subjects
Publications and source records attributed to F Caracciolo.
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A 55-year-old female with standard risk AML in second CR received an allogenic transplant from an HLA-matched sibling, using a nonmyeloablative conditioning regimen (NMST). On day +139, she rejected her graft with autologous reconstitution. She received a second NMST from a different HLA-matched sibling with an identical conditioning regimen and immunosuppression. On day +110, she rejected the second graft, with autologous reconstitution with blasts. She received a third allograft from the first sibling with a myeloablative busulfan-based conditioning regimen. She is now day +270, in CR, with full donor chimerism.
Cladribrine (2-CdA), a purine analogue active on both dividing and resting lymphocytes, plays an important role in the treatment of indolent lymphoproliferative malignancies such as Hairy Cell Leukemia (HCL), Chronic Lymphocytic Leukemia (CLL), Lymphoplasmocytic Lymphoma (LPL), Waldenström's Macroglobulinemia (WM). With the aim of evaluating the efficacy and toxicity of low dose 2-CdA, 15 lymphoplasmocytic lymphoma patients, not eligible for more aggressive or standard therapies, because of age or poor performance status, were treated with the drug at a dose of 5 mg/m2, once a week for six total courses. All patients showed disease progression. Fourteen patients were valuable for response. In eleven out of these 14 (85.7%) disease progression stopped, with 21% having good hematological responses (one CR and two PR). The treatment was generally well tolerated, without serious infectious events. This schedule may be appropriate for the management of patients where the aim of the treatment is control of disease progression.
Splenic Marginal Zone Lymphoma (SMZL) is a rare clinicopathological entity among marginal zone lymphomas. SMZL is an indolent lymphoma usually treated by splenectomy. A subset of patients is characterized by a more aggressive clinical course and poor prognosis. Treatment of these cases and second-line therapy for relapsed patients have not been yet identified. We report 10 cases treated with cladribrine (5 mg/m(2)/week) for six courses. Six patients (60%) achieved partial response, two patients (20%) achieved a complete response and the two remaining patients did not respond and died as a result of progression of the disease. The treatment was well tolerated. A total of 60% of the patients had an overall survival rate of 48 months and 24 months progression-free-survival was achieved by 37% with a median time of progression-free-survival of 17 months. Interestingly, in addition to a relevant percentage of hematological remission, some patients also experienced a molecular remission. We conclude that this treatment is safe and well tolerated and is able to induce a substantial number of responses. Our results suggest that this schedule is well tolerated and could be an useful alternative to splenectomy.
The main aim of this paper was to compare results of Genescan and real-time PCR methods in order to detect contamination in harvests from patients with follicular lymphoma. The secondary goal was to evaluate the efficacy of Rituximab as an in vivo purging agent. A total of 23 patients had been treated with CHOP followed by either high-dose therapy (12 patients) or high-dose plus Rituximab (11 patients), both followed by autologous transplantation. Results show that 86% of harvests from patients treated with Rituximab were PCR-negative compared to 14.3% from controls. Real-time PCR was more sensitive than Genescan PCR; quantitative analysis revealed a correlation between the amount of contamination in the harvests and relapse after transplantation. Whereas all patients reinfused with negative aphereses achieved complete remission and showed a significantly better 5-year PFS (100%) compared to those reinfused with contaminated samples (41%), a very low amount of contamination does not appear to negatively affect outcome, suggesting that determination of a cutoff in the contamination level of harvests could be useful. Results suggest that real-time PCR is superior to Genescan PCR to select transplantable harvests and confirm the ability of Rituximab as an in vivo purging tool for follicular lymphoma.
Two patients, observed at our institution, developed, after treatment with fludarabine, an early reappearance of metastatic primary solid cancers which were previously in long-lasting, complete remission. Patients had earlier suffered from a solid cancer considered cured and, subsequently, developed a lymphoid disorder treated with fludarabine. The two patients developed histologically confirmed hepatic metastasis from breast cancer and colic adenocarcinoma respectively 11 and 4 months after the beginning of fludarabine-therapy. Purine analogs have been reported to be effective against chronic lymphocytic leukemia and indolent lymphomas. However, these drugs induce severe immunodeficiency. In addition to the infectious diseases related to the treatment, the use of these drugs could facilitate the development of secondary neoplasms, related to the patient's impaired immunosurveillance. The surprisingly short latency between the therapy and the reappearance of non hematological cancers seen in our patients suggests that treatment with purine analogs may be involved in the reappearance of the tumors. In this regard, we suggest a possible role for purine analog-induced immunodeficiency in allowing the growth of previously undetected cancer cells rather than a direct drug-related mutagenic activity.
Seventy-two patients with non-Hodgkin's lymphoma were evaluated for the presence of molecular markers (IgH, bcl-1, bcl-2 rearrangement) on bone marrow, at diagnosis and after PBSCT, and on harvests in order to find a possible predictive role of minimal residual disease on treatment outcome. At diagnosis, 41 (59%) out of 69 available bone marrows showed molecular involvement. Fifty-six percent of leukaphereses were involved, mainly indolent lymphoma (P = 0.001) or advanced disease (P = 0.01). Ex vivo purging cleared only one stem collection out of 31 PCR-positive leukaphereses. Aggressive lymphomas showed both a longer overall survival (OS) (P = 0.03) and relapse-free survival RFS (P = 0.02) when transplanted with unpurged stem cells, whereas indolent NHL survival was not influenced by ex vivo purging. Twenty out of 26 samples taken during follow-up had bone marrow involvement at diagnosis. Of these, 15 cleared their bone marrow; both OS and RFS were significantly longer in the PCR-negative cases (P = 0.05 and P = 0.005). At 1 year after PBSCT, 75% of patients were PCR negative, with 50% molecular remissions; the relapse rate was 55% for patients still PCR positive vs 29% for those who were PCR negative. Thus, after high-dose chemotherapy, close molecular monitoring of MRD using qualitative PCR techniques seems to represent a reliable prognostic indicator.
Lymph node or bone marrow biopsy from sixty-one patients affected by aggressive non-Hodgkin lymphomas (NHL) were retrospectively evaluated to assess the histology at relapse. Eighteen cases (29.5%) were proven to have relapsed or persistent low-grade lymphoma after conventional therapy. In 5/18 patients association of low and high-grade lymphoma was detectable at diagnosis by bone marrow biopsy. In the remaining 13/18 no evidence of follicular lymphoma was detected at diagnosis. The outcome of these patients was compared to that of 43 patients relapsed without change in histology and treated by a second line therapy. Of these 43 patients, 13 were not responders (NR), 10 achieved a partial remission (PR) and 18 complete remission (CR). Two were lost during follow-up. The 18 patients with residual/relapsed indolent subtype received oral cyclophosphamide (100 mg/day for 15 days every month for six months): 3 of them had NR, 5 CR, and 10 PR. The overall survival (OS) median time was 39 months in low-grade resistant/relapsed patients and 20 months in patients with aggressive histology. OS at 24 months was 71 and 41%, respectively, (p < 0.02). Most of the patients with high-grade disease were refractory or relapsed after a median of five months, whereas cases with low-grade NHL showed a long lasting stable PR. We suggest that the higher grade patients with residual or relapsed low grade lymphoma were, in fact, transformed low-grade at diagnosis and, after removing the more aggressive component by chemotherapy, it is possible to manage these patients by conventional therapy for indolent lymphomas.
BACKGROUND: The safety, tolerability and efficacy of ropivacaine 1% vs lidocaine 2% for phacoemulsification using topical anesthesia during cataract surgery, are compared. METHODS: A prospective, randomized, double-blind study comparing two agents for topical anesthesia is reported. ENVIRONMENT: Operative Unit of Ophthalmology, general Hospital. 1893 consecutively patients were studied (ASA 1-3, 738 males, 1155 females, age 71.8+/-9.7 years, range 35-90 years) undergoing routine phacoemulsification under topical 2% lidocaine (group I) and 1% ropivacaine (group II). The mains outcome measures of the study were: - the total dose of local anesthetic for obtaining a reduction of corneal sensation measured with the Cochet-Bonnet esthesiometer (value>3); - the pain recorded with visual analogic scale and verbal scale at: T1 = the first injection of local anesthetic; T2 = corneal incision; T3 = the end of surgery; T4 = 1h after surgery; T5 = the first postoperative day; - any requirement for additional intraoperative injection anesthesia and systemic sedation when needed; - surgeon assessments of operative conditions and patient cooperation; - patients' subjective level of comfort; - complications. RESULTS: Topical anesthesia using lidocaine 2% was significantly more painful than the ropivacaine 1%. The onset of anesthesia adequate for surgery was similar in all two groups. There were differences between the groups with respect to perioperative analgesia because the VAS was significantly higher in lidocaine group than in ropivacaine group. There were no statistically differences between the two groups at the follow-up. Inadequate anesthesia was seen in 8.05% (74/919 patients) cases of group I vs 0.9% (22/974 patients) of group II. Sedation was needed only in 10 patients and 6 patients of group I and II respectively. The surgeon assessment showed more patient cooperation in the ropivacaine group (83%). Satisfactory comfort (level 1) was reported by 60.4% in the lidocaine group and 86.8% in the ropivacaine group. In both groups there were cases of postoperative epithelial edema (29 patients in group I vs 36 patients in group II) although it decreased after the first postoperative day. No other significant side-effects were observed with the use of either formulations. CONCLUSIONS: Lidocaine 2% and ropivacaine 1% were safe and effective agents in patients having phacoemulsification with IOL implantation. However, ropivacaine provides more good operative conditions than lidocaine for the surgeon and comfortable surgical circumstances for the patient.
BACKGROUND: Cholecystoenteric fistula (CF) is a rare complication of cholelithiasis. The aim of this study was to evaluate the safety and risk of complications when the laparoscopic approach is applied in patients with CF. METHODS: A questionnaire was mailed to all surgeons with experience of >100 cholecystectomies working in Naples, Italy, and the neighboring area. RESULTS: Between February 1990 and May 1999, 34 patients presented with cholecystoenteric fistula (0.2% of >15,000 laparoscopic cholecystectomies performed in the same period). These patients were allocated into two groups: the LT group (those who underwent laparotomic conversion after the diagnosis of CF), which consisted of 20 patients, four men and 16 women, with a mean age of 66.5 +/- 9.3 years (range, 46-85) and the LS group (laparoscopically treated patients), which consisted of 14 patients, three men and 11 women, with a mean age of 65.6 +/- 8.8 years (range, 51-74). They types of CF observed were as follows: in the former group of patients, cholecystoduodenal fistulas (n = 11, 55%), cholecystocolic fistulas (n = 5, 25%), cholecystojejunal fistulas (n = 3, 15%), and cholecystogastric fistulas (n = 1, 5%); in the latter group, cholecystoduodenal fistulas (n = 8, 5.1%), and cholecystocolic fistulas (n = 4, 28.6) and cholecystojejunal fistulas (n = 2, 14.3%). Stapler closure of CF was done in four LT patients and three LS patients with cholecystoduodenal fistula; it was also done in three LT patients and three LS patients with cholecystocolic fistula. Hand-sutured fistulectomy was performed in six LT patients and three LS patients with cholecystoduodenal fistula, in two LT patients with cholecystocolic fistula, and in all patients with cholecystojejunal or cholecystogastric fistula. There were no deaths or intraoperative complications in either group. One patient in the LT group developed a bronchopneumonia postoperatively. Postoperative hospital stay was significantly longer in LT patients-17 +/- 4 vs 3+/-1 days (p < 0.001). CONCLUSION: Cholecystoenteric fistula is an occasional intraoperative finding during laparoscopic cholecystectomy. The results of this study, which are based on the collective experiences of 19 surgeons, illustrate the growing success of the laparoscopic approach to this condition, including a decreasing rate of conversion to open surgery over the last 3 years.
The management of indolent lymphomas is still controversial. Intensive therapies may improve remission rate but in association with toxicity. Fludarabine and idarubicin are very active drugs in indolent lymphomas. This pilot trial was designed to evaluate the efficacy of a regimen comprising fludarabine, idarubicin and prednisone (FLIDA) in the treatment of low-grade non-Hodgkin's lymphoma at diagnosis. We have assessed the response of 16 adult patients (median age 57 years, range 45-71 years) treated on an outpatient basis: the overall response rate was 93.8 per cent (CR 43.8 per cent, PR > or = 50 per cent). The toxicity of this regimen was very low, with no relevant hematological and infectious complications.
BACKGROUND: The present study is a prospective evaluation of immediate preoperative laparoscopy compared to ultrasound/computed tomography (US/CT) staging for gastric cancer in a series of 100 patients observed at two major Italian hospitals from April 1995 through September 1996. METHODS: After a complete preoperative work-up all c-M0 patients underwent laparoscopy immediately prior to an eventual surgical exploration. pTNM was considered as the gold standard for the evaluation of the results. RESULTS: Laparoscopy detected 21 unsuspected M+ cases out of 100. As regards locally advanced tumors, laparoscopy showed a sensibility of 69.7% for T3 and 89.6% for T4, significantly higher than US/CT staging (23.2% and 48.3%, respectively; p < 0.02). In this series laparoscopic staging altered clinical staging in 58% of cases. CONCLUSIONS: This procedure plays two crucial roles in the preoperative evaluation of advanced gastric cancer: It makes it possible to avoid unnecessary surgical exploration in M+ cases and, to date, it represents the most reliable and economic tool for the selection of locally advanced tumors in the light of neoadjuvant treatment.
We investigated the pathogenetic relevance of hepatitis C virus (HCV) infection in mixed cryoglobulinemia (MC) with or without complicating B-cell Non-Hodgkin's lymphoma (NHL) in comparison with other immunological and lymphoproliferative disorders. The following groups of patients were studied: A) 25 patients with MC in 7 cases evolved into B-cell NHL; B) 25 healthy subjects; C) 22 patients with different systemic immune diseases; D) 24 patients with chronic HCV infection without MC; E) 25 patients with B-cell idiopathic NHL. Methods used included: i) Polymerase chain reaction (PCR) for HCV RNA detection in serum and peripheral blood mononuclear cells (PBMC) (uncultured or mitogen-stimulated); ii) Branched DNA (b-DNA) for HCV RNA quantification; iii) HCV genotyping by genotype-specific primers localized in the core region and by hybridization of amplification products of the 5' untranslated region (5'UTR), obtained with universal primers, using genotype-specific probes. Serum anti-HCV and HCV RNA were detected in 88% and 73% of MC patients, respectively, and in a significantly lower percentage of healthy controls and patients with autoimmune diseases. HCV RNA concentration was significantly lower in supernatants than in corresponding whole sera (p < 0.001). Plus-strand HCV RNA was detected in 81% of peripheral blood mononuclear cell (PBMC) samples and minus-strand in the majority of fresh or mitogen stimulated cells. All MC patients with NHL had HCV RNA sequences in PBMC. HCV genotype 2a/III was detected in MC patients with a prevalence that was significantly higher than in HCV infected patients without MC. Surprisingly, HCV markers (anti-HCV and/or HCV RNA) were found in 32% of patients with idiopathic NHL. These data suggest that HCV infection is involved in the pathogenesis of MC through both direct participation in the immune complex related vasculitis and by triggering the lymphoproliferative disorder underlying the disease. This latter disorder seems to be related to HCV lymphotropism which could also be responsible for the evolution of MC to malignant lymphoma. This study also suggests that HCV infection may be involved in the pathogenesis of idiopathic B-cell NHL through a similar pathogenetic mechanism.
Some lymphotropic viruses such as Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) have been proposed as causative agents of B cell non-Hodgkin's lymphoma (NHL). More recently, the presence of hepatitis C virus (HCV), which is both a hepatotropic and lymphotropic virus, has been reported in one third of B cell NHL patients. The aim of this study was to investigate in a series of B cell NHL the prevalence of three lymphotropic viruses, i.e. EBV, HHV-6 and HCV, in peripheral blood mononuclear cells (PBMC). Eighteen unselected B cell NHL patients (10 men, 8 women; mean age 62 +/- 12 years, range 31-77 years; mean disease duration 1.8 +/- 1.4 years) and 40 age- and sex-matched healthy controls were included in the study. In all cases, an acquired-immunodeficiency-syndrome-related lymphoma was excluded. By means of the polymerase chain reaction technique, EBV DNA, HHV-6 DNA and HCV RNA were detected in PBMC. HCV genomic sequences were significantly more frequent in PBMC of NHL patients than in controls (33 vs. 2.5%; p < 0.01); on the other hand, in the same two groups EBV DNA (39 vs. 60%; p = not significant) and HHV-6 DNA (22 vs. 32%; p = not significant) were present in a comparable percentage of individuals in the same two groups. The infection of PBMC by HCV alone was present in the majority (5 of 6) of HCV-positive NHL. These data support the implication of HCV infection in a statistically significant number of B cell NHL, whereas a possible co-operation between HCV and other well-known lymphotropic viruses seems to be excluded.
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Aggressive treatments in elderly patients with NHL are often responsible for acute complications and increased mortality. The present study confirms that P-VABEC is able to induce a high CR rate (71%), with an overall response rate of 92%. The 4-year actuarial OS was 45%, and the FFS was 38%. Despite these good results 57% of CRs relapsed in a relatively short time (median 9.5 months; range 2-47). Because of this we decided to evaluate the role of a consolidation schedule (CIP), including idarubicin and cisplatin. The toxicity of P-VABEC/CIP regimen was comparable to that of P-VABEC alone. After a median follow-up of 20 months (range 8-49), 93% of CR patients treated with P-VABEC-CIP were still in complete remission. The 4-year actuarial overall survival was 92%, and the failure-free survival in CR patients was 72%. The difference in OS and FFS between the two groups was statistically significant. These results suggest that a short course of additional therapy is feasible in elderly patients treated with P-VABEC and may increase the OS and FFS, without adding toxicity.
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