Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 30
Filter
3.
Leuk Suppl ; 1(Suppl 2): S12-3, 2012 Aug.
Article in English | MEDLINE | ID: mdl-27175232

ABSTRACT

Acute myeloid leukemia (AML) is a heterogeneous disease increasing in frequency owing to an aging population. Decisions on intensive induction treatments, intensification and allografting rely on the ability to divide an apparently homogeneous group according to risk. A wide range of clinical, cytogenetic and molecular variables may be used to inform this task; here we examine those variables useful in assessing prognosis for a patient with non-acute promyelocitic AML focusing on core binding factor leukemia. In clinical practice, when counseling an individual patient with AML, a range of well-known clinical variables (age, performance status and tumor burden) and genetic variables (cytogenetic and gene mutation) must be considered to better define the prognostic risk.

4.
Int J Immunogenet ; 38(4): 303-9, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21545408

ABSTRACT

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are represented by rare but life-threatening cutaneous adverse reactions to different drugs. Previous studies have found that in a Han Chinese population from Taiwan and other Asian Countries, a strong genetic association between HLA-class I alleles (B*15:02, B*58:01) and SJS and TEN was induced by carbamazepine and allopurinol, respectively. To identify genetic markers that covered the MHC region, we carried out a case-control association enrolling 20 Caucasian patients with SJS/TEN. Our patient series included 10 cases related to paracetamol, 7 to allopurinol and 3 to different drugs (plaquenil, itraconazol, nabumetone). Healthy controls were represented by 115 Caucasian bone marrow or stem cell donors. The HLA-A*, B*, C*, DRB1*, DQB1*, DQA1* and DPB1* genotyping were determined. The frequencies of HLA-A*33:03 as well as C*03:02 and C*08:01 were significantly higher in SJS/TEN patient subgroup showing allopurinol drug-induced severe cutaneous adverse reactions (SCAR) as compared to controls (28.6% vs 0%, P=0.00002, Pc=0.0011; 28.6% vs 0%, P=0.00002, Pc=0.001; 28.6% vs 0%, P=0.00002, Pc=0.001, respectively). In the same subgroup the frequencies of B*58:01, DRB1*15:02 and DRB1*13:02 alleles, although considerably higher than in control group (42.8% vs 5.2%, P=0.003; 28.6% vs 1.7%, P=0.005; 28.6% vs 3.5%, P=0.037, respectively), appeared no more statistically different after P correction (Pc=0.248; Pc=0.29; Pc=1.00, respectively). In addition, in 10 of the 20 SJS/TEN patient subgroup with paracetamol-induced SCAR no statistically significant association with HLA alleles could be found. However, in the same SJS/TEN patient subgroup showing allopurinol drug-induced SCAR, haplotype analysis indicated that B*58:01, DRB1*13:02 and DRB1*15:02 alleles, that in a single allele analysis lost statistical significance after P correction, may still confer susceptibility, because the B*58:01-DRB1*13:02 and DRB1*15:02-DQB1*05:02 are positively associated with the disease (14.2% vs 0.43%, P= 0.00001, Pc=0.00028; 14.2% vs 0.43%, P=0.00001, Pc=0.00028, respectively). Our results show that in contrast to SCAR-related to paracetamol, where HLA alleles do not appear to be involved, HLA molecules behave as a strong risk factor for SCAR-related to allopurinol even when a limited number of patients are considered.


Subject(s)
Alleles , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class I/genetics , Stevens-Johnson Syndrome/genetics , Adult , Aged , Case-Control Studies , Female , Gene Frequency/genetics , Haplotypes , Humans , Italy , Male , Middle Aged , Risk Factors , Stevens-Johnson Syndrome/immunology , Young Adult
5.
Diabetes Metab ; 35(2): 101-7, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19251448

ABSTRACT

AIM: To verify whether, with thorough practical and theoretical training, well-controlled, non-complicated diabetic patients can safely go diving underwater with no additional medical or metabolic risks. METHODS: Twelve diabetic patients participated in the study after undergoing training focused on their diabetic status. Two dives per day were scheduled during two five-day stays on the island of Ventotene (Italy). Capillary blood glucose (BG) was checked at 60, 30 and 10 minutes before diving, and corrective measures adopted if necessary, based on BG absolute levels and dynamics. A device for continuous subcutaneous glucose monitoring (CGM), expressly modified for the purpose, was worn during dives. RESULTS: Data were gathered from 90 dives; mean BG at 60, 30 and 10 minutes before diving was 205.8+/-69.6 mg/dL, 200.0+/-66.4 mg/dL and 200.5+/-61.0mg/dL, respectively. In 56 of the 90 dives, supplementary carbohydrates or insulin were necessary, but only one dive was interrupted on account of hypoglycaemic symptoms. Mean post-dive BG was 158.9+/-80.8 mg/dL. CGM recordings showed that glucose levels gradually decreased during the dives (nadir: -19.9%). CONCLUSION: Experienced, well-controlled, complication-free young diabetic patients can safely go scuba diving, provided that they apply a rigorous protocol based on serial pre-dive BG measurements. The specific variables of underwater diving do not appear to involve significant additional risks of hypoglycaemia.


Subject(s)
Blood Glucose Self-Monitoring , Blood Glucose/analysis , Diabetes Mellitus, Type 1/physiopathology , Diving , Adult , Blood Glucose Self-Monitoring/instrumentation , Blood Glucose Self-Monitoring/methods , Chi-Square Distribution , Female , Humans , Hypoglycemia/prevention & control , Male , Motor Activity , Safety
6.
Ann Oncol ; 19(7): 1331-1335, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18344536

ABSTRACT

BACKGROUND: To evaluate the clinical outcome of patients with relapsed or refractory follicular lymphoma treated with immunochemotherapy, in vivo purging and high-dose therapy with autotransplant. PATIENTS AND METHODS: Sixty-four patients were enrolled in the trial. Primary end point was progression-free survival (PFS). Secondary end points were the in vivo purging effect on stem-cell harvest and the impact of molecular response on the outcome. RESULTS: At enrollment, 59% of patients were PCR+ for bcl-2 rearrangement in bone marrow (PCR-informative). After the immunochemotherapy, before mobilization, 97% obtained complete response or partial response and 87% of patients informative for bcl-2 were molecularly negative. Sixty-one patients proceeded to in vivo purging and peripheral blood stem cell (PBSC) mobilization with rituximab and high-dose AraC. The median number of CD34+ cells collected was 16.6 x 10(6)/kg. Of 33 PCR-informative patients, the harvests resulted in PCR- in all. Fifty-eight patients received high-dose therapy and autotransplant of in vivo purged PBSC. After a median follow-up of 3.5 years, 41 patients are in complete remission. Five-year PFS is 59%. CONCLUSION: This study demonstrates that patients with advanced relapsed or refractory follicular lymphoma treated with immunochemotherapy, in vivo purging and autotransplant may obtain long-lasting PFS. In bcl-2-positive patients, in vivo purging allows the harvest of lymphoma-free PBSC. Absence of the bcl-2 rearrangement after autotransplant is associated with persistent clinical remission.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Purging/methods , Lymphoma, Follicular/therapy , Peripheral Blood Stem Cell Transplantation , Adult , Anthracyclines/administration & dosage , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Murine-Derived , Antigens, CD20/metabolism , Antigens, CD34/analysis , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Disease Progression , Disease-Free Survival , Doxorubicin/administration & dosage , Drug Administration Schedule , Etoposide/administration & dosage , Female , Follow-Up Studies , Genes, bcl-2 , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization , Humans , Immunologic Factors/administration & dosage , Immunosuppressive Agents/administration & dosage , Kaplan-Meier Estimate , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/pathology , Male , Middle Aged , Multivariate Analysis , Recurrence , Remission Induction , Rituximab , Time Factors , Transplantation, Autologous , Treatment Outcome , Vincristine/administration & dosage
7.
Bone Marrow Transplant ; 39(10): 631-5, 2007 May.
Article in English | MEDLINE | ID: mdl-17384656

ABSTRACT

Antifungal therapy may be unable to eradicate invasive mycosis in leukemia patients. The presence of persisting pulmonary nodules owing to mycosis seems to increase the risk of fungal relapse after chemotherapy and transplant procedures. Between 1997 and 2004, 10 acute leukemia patients underwent pulmonary surgery for invasive mycosis. The median time from diagnosis of mycosis to surgery was 135 days (range 21-147). Three patients underwent emergency surgery, owing to hemoptysis. In the other seven patients with nodule/cavitation remaining after antifungal treatment, surgery (three wedge resections, four lobectomies) was scheduled before transplant. Pathologic examination confirmed two aspergillosis and three zygomycosis. The only side effect was pneumothorax in one case. Nine patients were considered cured. Six patients underwent bone marrow transplantation (three allogeneic, three autologous) with antifungal prophylaxis without relapse during the transplant procedure. In selected patients scheduled for bone marrow transplantation, surgical resection of localized pulmonary fungus nodules combined with antifungal prophylaxis seem to be an effective treatment for preventing mycotic relapse.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Marrow Transplantation/adverse effects , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/therapy , Lung Diseases, Fungal/etiology , Lung Diseases, Fungal/surgery , Adult , Aged , Antifungal Agents/therapeutic use , Aspergillosis/drug therapy , Aspergillosis/etiology , Aspergillosis/prevention & control , Aspergillosis/surgery , Female , Humans , Leukemia, Myeloid, Acute/complications , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/prevention & control , Male , Middle Aged , Mucormycosis/drug therapy , Mucormycosis/etiology , Mucormycosis/prevention & control , Mucormycosis/surgery , Recurrence
8.
Bone Marrow Transplant ; 38(6): 413-6, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16878144

ABSTRACT

Systematic data on the ability of pegfilgrastim to mobilize stem cells after chemotherapy are scarce. We evaluated the efficacy of a single 6 mg dose of pegfilgrastim for mobilizing peripheral blood stem cells (PBSC) in aggressive lymphoma patients. Between July 2004 and October 2005, 17 aggressive non-Hodgkin's lymphoma and 11 poor-risk Hodgkin's lymphoma were treated with cycles containing cisplatin-aracytin. At the end of chemotherapy, the patients received 6 mg of pegfilgrastim. Duration of grade 4 neutropenia, adverse events, time to neutrophil recovery, peak and harvest of CD34+ cells were recorded. Twenty-seven out of 28 patients harvested a median of 17.3 x 10(6)/CD34+ cells (range 2.5-28.9) after a median of 9 days (range 8-12 days), with a single apheresis procedure in 25 cases. All patients had grade 3-4 neutropenia, median duration 3 days. The only adverse event was mild bone pain. To date, 13 patients have been autografted with a median of 15.4 x 10(6) CD34+ pegfilgrastim-mobilized cells per kg (range 2.5-28.9) with rapid and sustained engraftment. Mobilization, harvesting and autografting of pegfilgrastim-mobilized PBC can be successfully achieved in pretreated patients with aggressive lymphoma.


Subject(s)
Antigens, CD34 , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization , Hodgkin Disease/therapy , Lymphoma, Non-Hodgkin/therapy , Peripheral Blood Stem Cell Transplantation , Adult , Aged , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cytarabine/administration & dosage , Cytarabine/adverse effects , Female , Filgrastim , Hematopoietic Stem Cell Mobilization/adverse effects , Hodgkin Disease/complications , Humans , Lymphoma, Non-Hodgkin/complications , Male , Middle Aged , Neutropenia/etiology , Pain , Peripheral Blood Stem Cell Transplantation/adverse effects , Polyethylene Glycols , Recombinant Proteins , Transplantation, Autologous
9.
Leukemia ; 18(1): 57-62, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14586480

ABSTRACT

Chronic lymphocytic leukemia (CLL) cells could be undetectable by flow cytometry or polymerase chain reaction after sequential treatment with fludarabine and Campath-1H. Concern has been raised regarding the ability to mobilize sufficient peripheral blood progenitor cells (PBPCs) for autografting after purine analogues, and there are few data about PBPC collection after Campath-1H. In all, 16 CLL patients responding to sequential chemo-immunotherapy entered the study. In 10, mobilization regimen consisted of granulocyte colony-stimulating factor (G-CSF) 5-10 microg/kg/die. Patients failing mobilization or not achieving the target of 2.5 x 10(6) CD34+ cells/kg underwent a second attempt using intermediate-dose (ID) Ara-C, 800 mg/m(2) every 12 h for six doses+G-CSF. PBPC collection after G-CSF alone was successful in two out of 10 patients. An adequate number of CD34+ cells were collected after ID Ara-C+G-CSF in eight patients failing the mobilization with G-CSF alone and in five out of six who did not receive G-CSF before. Greater yields of PBPCs were collected with Ara-C+G-CSF compared with G-CSF alone (13.8 vs 3.3). The extrahematologic toxicity was manageable. In conclusion, PBPC collection is feasible in CLL patients treated with sequential therapy including fludarabine and Campath-1H. Excellent yields were obtained in 92.8% of patients primed with ID Ara-C+G-CSF.


Subject(s)
Antigens, CD34/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cells/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Vidarabine/analogs & derivatives , Adult , Alemtuzumab , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Antibodies, Neoplasm/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cytarabine/administration & dosage , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Leukocytes/physiology , Male , Middle Aged , Time Factors , Transplantation, Autologous , Vidarabine/administration & dosage
12.
Leuk Lymphoma ; 43(3): 657-9, 2002 Mar.
Article in English | MEDLINE | ID: mdl-12002776

ABSTRACT

Mucormycosis infections, caused by fungi of the families Rhizopus, Mucor or Absidia, are typically rapidly progressive and often fatal. We report a 27-year-old male with acute myeloid leukemia (AML) developing an invasive pulmonary-CNS mucormycosis during the neutropenic period after salvage induction chemotherapy; the infection was successfully controlled with surgery and antifungal therapy. The patient received two courses of consolidation chemotherapy and underwent autologous stem cells transplantation (ASCT) while receiving secondary antifungal systemic prophylaxis with liposomal Amphotericin B (L-AMB, Ambisome). There was no clinical, radiological or microbiological evidence of mycotic reactivation during the bone marrow transplantation (BMT) procedure.


Subject(s)
Leukemia, Myeloid/complications , Mucormycosis/therapy , Stem Cell Transplantation , Acute Disease , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cerebellar Diseases/chemically induced , Cerebellar Diseases/microbiology , Cerebellar Diseases/therapy , Contraindications , Humans , Leukemia, Myeloid/microbiology , Leukemia, Myeloid/therapy , Lung Diseases, Fungal/chemically induced , Lung Diseases, Fungal/therapy , Male , Mucormycosis/chemically induced , Mucormycosis/pathology , Opportunistic Infections/chemically induced , Opportunistic Infections/therapy , Transplantation, Autologous
13.
Bone Marrow Transplant ; 29(6): 473-7, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11960265

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/radiotherapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/radiotherapy , Mediastinal Neoplasms/drug therapy , Mediastinal Neoplasms/radiotherapy , Thorax/pathology , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/administration & dosage , Bleomycin/therapeutic use , Combined Modality Therapy/methods , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Drug Administration Schedule , Etoposide/administration & dosage , Etoposide/therapeutic use , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Lymphoma, B-Cell/surgery , Lymphoma, Large B-Cell, Diffuse/surgery , Male , Mediastinal Neoplasms/surgery , Middle Aged , Prednisone/administration & dosage , Prednisone/therapeutic use , Prognosis , Risk Factors , Sclerosis , Thorax/drug effects , Thorax/radiation effects , Transplantation, Autologous , Vincristine/administration & dosage , Vincristine/therapeutic use
14.
Br J Haematol ; 116(1): 229-35, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11841421

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Bone Marrow Purging , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation , Lymphoma/therapy , Adult , Antibodies, Monoclonal/pharmacokinetics , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Agents/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Gene Rearrangement , Genes, bcl-2 , Half-Life , Humans , Lymphoma, Follicular/therapy , Lymphoma, Mantle-Cell/therapy , Male , Metabolic Clearance Rate , Middle Aged , Polymerase Chain Reaction , Prednisone/administration & dosage , Recurrence , Rituximab , Transplantation, Autologous , Vincristine/administration & dosage
15.
Am J Hematol ; 68(4): 231-6, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11754411

ABSTRACT

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.


Subject(s)
Aspergillosis/etiology , Hematologic Neoplasms/virology , Adult , Aged , Antifungal Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Aspergillosis/diagnosis , Aspergillosis/drug therapy , Bone Marrow Transplantation , Disease Management , Female , Hematologic Neoplasms/complications , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Neutropenia/complications , Retrospective Studies , Treatment Outcome
16.
Bone Marrow Transplant ; 28(9): 835-9, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11781643

ABSTRACT

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.


Subject(s)
Cisplatin , Cyclophosphamide , Dexamethasone , Etoposide , Hematopoietic Stem Cell Mobilization , Multiple Myeloma/therapy , Adult , Aged , Antigens, CD34/analysis , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blood Cell Count , Bone Marrow Purging , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Granulocyte Colony-Stimulating Factor , Humans , Male , Middle Aged , Multiple Myeloma/drug therapy , Treatment Outcome
17.
Hum Mol Genet ; 9(15): 2297-304, 2000 Sep 22.
Article in English | MEDLINE | ID: mdl-11001933

ABSTRACT

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.


Subject(s)
Alternative Splicing , Leukemia, Myeloid/genetics , Protein Tyrosine Phosphatases/genetics , RNA Editing , Acute Disease , Base Sequence , HL-60 Cells , Humans , Intracellular Signaling Peptides and Proteins , Introns , Molecular Sequence Data , Protein Tyrosine Phosphatase, Non-Receptor Type 11 , Protein Tyrosine Phosphatase, Non-Receptor Type 6 , Protein Tyrosine Phosphatases/metabolism , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , SH2 Domain-Containing Protein Tyrosine Phosphatases , Sequence Analysis, RNA , Tumor Cells, Cultured
18.
Cancer Genet Cytogenet ; 119(1): 26-31, 2000 May.
Article in English | MEDLINE | ID: mdl-10812167

ABSTRACT

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.


Subject(s)
Alleles , Gene Duplication , Leukemia, Myeloid/genetics , Mast Cells/pathology , Mutation , Proto-Oncogene Proteins c-kit/genetics , Trisomy , Acute Disease , Base Sequence , DNA Primers , Humans , In Situ Hybridization, Fluorescence
20.
Blood Cells Mol Dis ; 24(2): 262-70, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9714703

ABSTRACT

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.


Subject(s)
Amino Acid Substitution , Gene Expression Regulation, Leukemic/genetics , Leukemia, Myeloid, Acute/pathology , Mast Cells/cytology , Neoplastic Stem Cells/cytology , Point Mutation , Proto-Oncogene Proteins c-kit/genetics , Alleles , Animals , Antigens, CD34/analysis , Bone Marrow/pathology , Cell Differentiation/genetics , Cell Division/genetics , DNA, Neoplasm/genetics , Disease Progression , Fatal Outcome , Humans , Leukemia, Mast-Cell/pathology , Leukemia, Myeloid, Acute/genetics , Male , Mast-Cell Sarcoma/pathology , Mice , Middle Aged , Proto-Oncogene Proteins c-kit/analysis , Rats , Reverse Transcriptase Polymerase Chain Reaction , Stem Cell Factor/physiology , Tumor Cells, Cultured
SELECTION OF CITATIONS
SEARCH DETAIL
...