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Biomedical subjects

R Cairoli

Publications and source records attributed to R Cairoli.

18 recordsLinked to original sources
PubMed2002

Efficacy of an early intensification treatment integrating chemotherapy, autologous stem cell transplantation and radiotherapy for poor risk primary mediastinal large B cell lymphoma with sclerosis.

The aim of our study was to evaluate the impact of an early intensification programme including chemotherapy (CHT), autologous stem cell transplantation (ASCT) and radiation therapy (RT) in patients with primary mediastinal large B cell lymphoma (MLCL) with sclerosis presenting with adverse prognostic factors. Between 1993 and 1999, 19 patients with MLCL were referred to our institution. Four patients were classified as low risk according to the age-adjusted International Prognostic Index (AA-IPI). Fifteen (79%) were categorised in the high-intermediate or high risk group and were considered eligible for ASCT. Induction therapy consisted of VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin) for 12 weeks. After induction therapy the four low risk patients achieved a complete remission (CR) and did not undergo ASCT. Of the 15 poor risk patients, five achieved CR, seven partial remission (PR), and three showed refractory disease (RD). All these patients received mobilising therapy consisting of high-dose cyclophosphamide. After peripheral stem cell (PSC) collection, to obtain a greater tumor mass reduction before transplantation, the seven patients in PR underwent further treatment with high-dose etoposide and those with RD received two cycles of DHAP (dexamethasone, cytarabine and cisplatin). At the time of ASCT, seven patients were in CR, six in PR and two had RD. After transplantation using BEAM as preparative regimen, all patients but one achieved a CR. Seven patients with minimal (<25%) residual mass at computed tomography scan received further mediastinal RT even if they had a negative Ga(67) scan. At a median follow-up of 35 months from transplantation the disease free survival is 93%. The outcome following this programme of early intensification in poor prognosis MLCL results in a high incidence of durable remissions even in patients with refractory disease.

Adolescent↗
PubMed2002

A sequence of immuno-chemotherapy with Rituximab, mobilization of in vivo purged stem cells, high-dose chemotherapy and autotransplant is an effective and non-toxic treatment for advanced follicular and mantle cell lymphoma.

Options for relapsed/refractory indolent lymphoma include chemotherapy, immunotherapy and high-dose therapy with autologous support. The best combination of these approaches, however, is not defined. We treated 10 patients with relapsed/refractory follicular (n = 7) or mantle cell lymphoma (n = 3) using chemotherapy, immunotherapy, high-dose therapy and autotransplant in a sequence of four phases, each designed to play a specific role in tumour eradication. After the debulking with VACOP-B (doxorubicin, cyclophosphamide, etoposide, vincristine, prednisone, bleomycin) (phase 1), 9/10 patients responded but none achieved a molecular response. After the immuno-chemotherapy phase, which combined Rituximab with vincristine and cyclophosphamide, seven patients were in complete response (CR) and three in good partial response (PR), and all those with a molecular marker of disease showed a disappearance of the signal from marrow and blood. Phase 3, which coupled high-dose cytarabine with Rituximab, was effective in mobilizing an adequate number of progenitor cells that were polymerase chain reaction negative in all informative cases. Phase 4 consisted of high-dose therapy with autologous support followed by two doses of Rituximab. Autograft was performed in nine patients. The haematopoietic recovery was as expected. This sequence of chemotherapy, immuno-chemotherapy, stem cell mobilization with in vivo purging and autotransplant, organized in four blocks of treatment, was simple to administer and devoid of toxic effects. It permits rapid attainment of clinical and molecular response and enables the harvest of lymphoma-free peripheral blood progenitor cells even in heavily pretreated patients with relapsed or refractory disease.

Adult↗
PubMed2001

Invasive aspergillosis in haematological malignancies: clinical findings and management for intensive chemotherapy completion.

Sixty-one cases of Aspergillus infection (35 acute myeloid leukemia, 15 acute lymphoid leukemia, one myelodysplastic syndrome, two aplastic anemia, eight non-Hodgkin's lymphoma) seen in our department between January 1989 and July 1999 were studied retrospectively to evaluate the clinical characteristics, to ascertain the factors that influenced the outcome from mycotic infections, and whether early diagnosis and prolonged therapy permitted completion of scheduled intensive chemotherapy and bone marrow transplantation (BMT) without fungal recurrence. The patients were divided into three diagnostic categories: proven aspergillosis (autoptic or histologic diagnosis) n = 39, probable aspergillosis (radiological diagnosis with positive microbiology) n = 9, and possible aspergillosis (radiological diagnosis alone) n = 13. In the same period among 675 acute leukemia patients the incidence of proven or probable aspergillosis was 7.1%. At onset of infection 92% of patients were neutropenic (< 0.5 x 10(9)/L). The most frequent site of infection was the lung (90%); disseminated disease was present in 20 patients. Among 44 assessable patients, 12 (27%) failed to respond to early antifungal therapy and died. Thirty-two patients were cured with antifungal treatment, three of five nonneutropenic with only itraconazole, the others with amphotericin B 1 mg/Kg/day with or without itraconazole subsequently or with liposomal amphotericin, Ambisome, if renal toxicity occurred. Twenty-four of 29 neutropenic responders, all affected by acute leukemia, continued scheduled intensive chemotherapies. Pulmonary lobectomy was successfully combined with medical treatment in two cases before scheduled BMT. After infection nine patients were submitted to BMT (six allo, one marrow unrelated donor (MUD), two auto) with Ambisome or itraconazole as secondary prophylaxis without fungal relapse (follow-up: 25-99 months). The median time from fungal infection to transplant was five months, range 3-10. Thirteen of 29 surviving patients had leukemia relapse, but only three (23%) of these showed also fungal infection recurrence. In conclusion, a high index of suspicion and careful clinical and radiological examinations are the key to identifying infected patients early and to programming the following therapeutic steps. Above all in leukemia patients, prompt and aggressive administration of antifungal agents seems to improve the outcome of invasive fungal disease and to permit intensive chemotherapy completion and transplant.

Adult↗
PubMed2001

DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) is an effective regimen for peripheral blood stem cell collection in multiple myeloma.

DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) has proved to be an effective salvage therapy for refractory-relapsed MM patients. Little is known, however, about its potential as mobilizing therapy. The aim of this study was to evaluate the efficacy of DCEP in mobilizing PBSC and to define its toxicity. Fifty-five MM patients received DCEP followed by G-CSF as part of high-dose programs including autologous transplantation. At the time of mobilization, 40 patients had previously received VAD only, and 15 alkylating agents. Mobilization was successful (minimum number of CD34(+) cells 2 x 10(6)/kg) in 48/55 patients (87%), and 41/55 patients (75%) collected >4 x 10(6)/kg CD34(+) cells. Of the seven patients who did not mobilize stem cells, five (71%) had been previously exposed to alkylating agents. The median number of CD34(+) cells harvested was 5.8 x 10(6)/kg (range 2.1-22.4). There was no treatment-related mortality. The side-effects of DCEP were always tolerable. No neutropenia <1000/microl nor thrombocytopenia <50,000/microl were observed. No patient required transfusion as a consequence of therapy, or hospitalization for septic complications. In conclusion, DCEP, in addition to its demonstrated anti-tumor activity, is an effective regimen for mobilizing peripheral blood progenitor cells in myeloma patients, with little or no side-effects. These properties render DCEP a useful regimen for the debulking and mobilization phase of high-dose programs for multiple myeloma.

Adult↗
PubMed2000

RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia.

The SH2 domain-containing tyrosine phosphatase PTPN6 (SHP-1, PTP1C, HCP) is a 68 kDa cytoplasmic protein primarily expressed in hematopoietic cell development, proliferation and receptor-mediated mitogenic signaling pathways. By means of direct dephosphorylation, it down-regulates a broad spectrum of growth-promoting receptors, including the Kit tyrosine kinase, activated to elicit a prominent cascade of intracellular events by stem cell factor binding. The pivotal contribution of PTPN6 in modulating myeloid cell signaling has been revealed by the finding that shp-1 mutation is responsible for the overexpansion and inappropriate activation of myelomonocytic populations in motheaten (me/me) and motheaten viable (me(v)/me(v)) mice. Association of PTPN6 with c-Kit and negative modulation of the myeloid leukocyte signal transduction pathways prompted us to examine the expression of the protein tyrosine phosphatase PTPN6 gene in CD34(+)/CD117(+) blasts from acute myeloid leukemia patients. We identified and cloned cDNAs representing novel PTPN6 mRNA species, derived from aberrant splicing within the N-SH2 domain leading to retention of intron 3. Sequence analysis of cDNA clones revealed multiple A-->G editing conversions. The editing of PTPN6 mRNA mainly occurred as an A-->G conversion of A(7866), which represents the putative branch site in IVS3 of PTPN6 mRNA. Evidence that editing of A(7866) abrogates splicing has been obtained in vitro by using an edited clone and its backward clone generated by site-directed mutagenesis. The level of the aberrant intron-retaining splice variant, evaluated by semi-quantitative RT-PCR, was lower in CD117(+)-AML bone marrow mononuclear cells at remission than at diagnosis, suggesting the involvement of post-transcriptional PTPN6 processing in leukemogenesis.

Acute Disease↗
PubMed2000

Trisomy 4 leading to duplication of a mutated KIT allele in acute myeloid leukemia with mast cell involvement.

A G-->T transversion at nucleotide 2467 of the c-KIT gene leading to Asp816-->Tyr (D816Y) substitution in the phosphotransferase domain has been previously identified in a patient with rapidly progressing AML-M2 and mast cell involvement; the patient's blasts had a 47,XY, +4,t(8;21)(q22;q22) karyotype. Herein we confirm the simultaneous presence of both major chromosomal changes by multicolor fluorescence in situ hybridization (FISH) on interphase CD34+ mononuclear cells. By setting up culture leukemic blasts, spontaneous differentiation of adherent cells with mast-cell like features was proved by histochemical and immunoenzymatic analyses. Fluorescence in situ hybridization evidence of trisomy 4 confirmed the origin of differentiated cells from the leukemic blasts. Semiquantitative polymerase chain reaction (PCR) and phosphoimage densitometry of wild-type and mutated KIT alleles on bone marrow blasts made it possible to demonstrate that chromosome 4 trisomy led to a double dosage of the mutated KIT allele. This finding, and that of trisomy 7 and MET mutation in hereditary renal carcinoma represent the only cases of human tumors in which an increased number of chromosomes carrying an oncogene activated by point mutation have been detected.

Acute Disease↗
PubMed1998

In vivo differentiation of mast cells from acute myeloid leukemia blasts carrying a novel activating ligand-independent C-kit mutation.

The primary role of protooncogene c-kit in mast cell differentiation is supported by the development of mast cells from CD34+/CD117+(c-kit) myeloid precursors. Growth factor independence, neoplastic transformation and differentiation of mast cells were found in association with c-kit activating mutations in both murine and human mastocytoma and mast cell diseases. We have identified a novel c-kit mutation (D816Y) in peripheral blood mononuclear cells from a patient with AML (M2), massive presence of mast cells in bone marrow and rapid progression of the disease. The mutation, a G-->T transversion at nt 2467 of the c-kit gene resulting in Asp816-->Tyr substitution, corresponds to the D814Y and D817Y mutations identified and characterized in the murine P815 mastocytoma and the rat RBL-2H3 mast cell leukemia cell lines. The absence of SCF transcripts that we found by RTPCR in the patient's blasts indicates that, also in humans, this activating mutation leads to SCF independent growth. The expression of the mutant allele on Kit signaling may be further enhanced by trisomy of chromosome 4 (carrying the c-kit gene) in the patient's blasts. From these findings it is concluded that mast cells could be generated from a leukemic CD34/CD117-positive clone, that combines the antigenic expression of mast cell precursor to the growth and differentiation factor-independence which was derived by the c-kit D816Y mutation.

Alleles↗
PubMed1996

PML/RAR alpha transcripts monitored by polymerase chain reaction in acute promyelocytic leukemia during complete remission, relapse and after bone marrow transplantation.

The translocation t(15;17)(q24;q21), unique to acute promyelocytic leukemia (APL), gives rise to PML/RAR alpha fusion transcripts detected by the sensitive reverse transcriptase-polymerase chain reaction (PCR) technique. PCR may help in the diagnosis and in monitoring minimal residual disease. Reversion of PCR to negative is obtained by chemotherapy (CT) alone or in combination with all-trans retinoic acid (ATRA). Here we show a serial PCR study of 10 APL cases. Five cases were studied at the time of diagnosis, and all were PCR positive for the rearranged transcripts (three bcr1 type, two bcr3 type). Seven cases in complete remission (CR) after one cycle of induction CT were persistently PCR negative, one case in CR after ATRA rescue was persistently PCR positive (bcr1 type), one patient (bcr3 type) relapsed 15 months after the PCR-negative CR and one patient died early. Seven patients underwent bone marrow transplantation (BMT) (five allogeneic, two autologous). One of them died early after take of the allogeneic BMT, the other six cases studied by serial PCR were persistently negative. At a median follow-up of 31 months (range 9-39), none of these six cases had relapsed. PCR data characterize the CR at the molecular level and evaluate the efficacy of different treatments, including BMT. The data may help to define a standardized schedule for PCR follow-up, and are also potentially useful to establish the time required before judging patients with persistently negative PCR to be cured. BMT as post-induction treatment in first CR is also discussed.

Adult↗
PubMed1995

Detection by polymerase chain reaction of BCR/ABL transcripts in myeloproliferative diseases at time of diagnosis and for monitoring chronic myelogenous leukaemia patients after bone marrow transplantation.

The Philadelphia chromosome t(9;22)(q34;q11) is a cytogenetic marker for chronic myelogenous leukaemia (CML), and is also present in some acute leukaemias. The translocation in CML gives rise to two BCR/ABL chimeric transcripts (b3a2 and b2a2) encoding a 210-kD tyrosine kinase protein. These leukaemia-specific transcripts can be detected easily by the reverse transcriptase polymerase chain reaction (PCR). PCR has improved the possibility of detecting minimal residual leukaemia cells in Ph-positive patients, especially after bone marrow transplantation (BMT). With PCR, we looked for BCR/ABL transcripts in 30 patients with CML and 4 with essential thrombocythaemia at time of diagnosis, finding a significant difference in the platelet counts of CML patients carrying b3a2 or b2a2 transcripts. The BCR/ABL transcript was monitored by PCR in 6 CML patients after BMT. The usefulness of PCR in clinical practice at time of diagnosis, and the biological and clinical significance of positive/negative PCR results, in patients with transplants, are discussed.

Adult↗
PubMed1995

Saccharomyces cerevisiae fungemia with granulomas in the bone marrow in a patient undergoing BMT.

A 48-year-old woman underwent allogeneic BMT for CML in chronic phase. One day +180 she experienced fever (37.8 degrees C) and skin rash. Blood cultures from the Hickman catheter and peripheral veins were positive for Saccharomyces cerevisiae. The clinical course of this patient indicates that Saccharomyces should be considered as a possible cause of fever of otherwise unknown origin.

Bone Marrow Diseases↗
PubMed1983

[Separation of high density lipoproteins (HDL) using zonal ultracentrifugation in patients with apolipoprotein AI Milano variant].

Investigations of HDL with zonal ultracentrifugation were carried out in three patients with apolipoprotein AIMilano. HDL in patients with AIMilano apolipoprotein are characterized by the practically total absence of HDL2. The HDL3 peak is broader than normal. In spite of the marked reduction or practically total absence of HDL2, which is believed to be a protective factor against atherosclerosis, our patients show no signs of clinical atherosclerosis.

Adult↗
PubMed1982

[Acipimox treatment of hyperlipidemia type II].

The hypolipidemic effect of acipimox, a new inhibitor of lipolysis, was investigated in a double blind crossover trial versus placebo. The trial showed an appreciable and significant reduction in total cholesterol (-14%) and of LDL cholesterol (-20%), a slight but significant increase in HDL cholesterol (+6%), and only a slight diminution of triglycerides and VLDL cholesterol.

Adult↗
PubMedDate not supplied

Untunnelled central venous catheters in the treatment of acute leukemia.

Ninety-eight untunnelled central venous catheters were positioned in the subclavian or internal jugular vein in 42 patients with acute leukemia. The procedure was feasible at bedside and carried a risk of catheter-related infection of 21%, similar to that of tunnelled catheters. The persistence of exit-point infection is the main route of infection and requires catheter removal.

Acute Disease↗