Biomedical subjects

G Visani

Publications and source records attributed to G Visani.

At least 91 records · Page 5Linked to original sources

PubMed1996

Interleukin-9 stimulates the proliferation of human myeloid leukemic cells.

Human interleukin-9 (IL-9) stimulates the proliferation of primitive hematopoietic erythroid and pluripotent progenitor cells, as well as the growth of selected colony-stimulating factor (CSF)-dependent myeloid cell lines. To further address the role of IL-9 in the development of acute leukemia, we evaluated the proliferative response of three leukemic cell lines and 32 primary samples from acute myeloblastic leukemia (AML) patients to recombinant human (rh)-IL-9 alone and combined with rh-IL-3, granulocyte-macrophage CSF (GM-CSF), and stem cell factor ([SCF] c-kit ligand). The colony-forming ability of HL60, K562, and KG1 cells and fresh AML cell populations upon IL-9 stimulation was assessed by a clonogenic assay in methylcellulose, whereas the cell-cycle characteristics of leukemic samples were determined by the acridine-orange flow cytometric technique and the bromodeoxyuridine (BRDU) incorporation assay. In addition, the terminal deoxynucleotidyl transferase assay (TDTA) and standard analysis of DNA cleavage by gel electrophoresis were used to evaluate induction of prevention of apoptosis by IL-9. Il-9, as a single cytokine, at various concentrations stimulated the colony formation of the three myeloid cell lines under serum-containing and serum-free conditions, and this effect was completely abrogated by anti-IL-9 monoclonal antibodies (MoAbs). When tested on fresh AML samples, optimal concentrations of IL-9 resulted in an increase of blast colony formation in all the cases studied (mean +/- SEM: 19 +/- 10 colony-forming unit-leukemic [CFU-L]/10(5) cells plated in control cultures v 107 +/- 32 in IL-9-supplemented dishes, P < .02). IL-9 stimulated 36.8% of CFU-L induced by phytohemagglutinin-lymphocyte-conditioned medium (PHA-LCM), and it was the most effective CSF for promoting leukemic cell growth among those tested in this study (i.e., SCF, IL-3, and GM-CSF). The proliferative activity of IL-9 was also observed when T-cell-depleted AML specimens were incubated with increasing concentrations of the cytokine. Addition of SCF to IL-9 had an additive or synergistic effect of the two cytokines in five of eight AML cases tested for CFU-L growth (187 +/- 79 colonies v 107 +/- 32 CFU-L, P = .05). Positive interaction was also observed when IL-9 was combined with IL-3 and GM-CSF. Studies of cell-cycle distribution of AML samples demonstrated that IL-9 alone significantly augmented the number of leukemic cells in S-phase in the majority of cases evaluated. IL-9 and SCF in combination resulted in a remarkable decrease of the G0 cell fraction (38.2% +/- 24% v 58.6% +/- 22% of control cultures, P < .05) and induced an increase of G1- and S-phase cells. Conversely, neither IL-9 alone nor the combination of IL-9 and SCF had any effect on induction or prevention of apoptosis of leukemic cells. In summary, our results indicate that IL-9 may play a role in the development of AML by stimulating leukemic cells to enter the S-phase rather than preventing cell death. Moreover, IL-9 acts synergistically with SCF for recruiting quiescent leukemic cells in cell cycle.

Adolescent↗

PubMed1996

In vitro culture with prednisolone increases BCL-2 protein expression in adult acute lymphoblastic leukemia cells.

The presence of BCL-2 gene rearrangement has been detected also in cellular populations lacking the t(14;18) chromosomal translocation, such as B-lineage acute lymphoblastic leukemia (ALL) cells. It has been reported that overexpression of BCL-2 is related to resistance to glucocorticoid-induced apoptosis. In this study, we aimed to evaluate whether in vitro culture with prednisolone (PDN) could modify the expression of BCL-2 protein. ALL cells from 21 patients were incubated for 72 hr with or without a minimally lethal (IC12) dose of PDN. In vitro culture with PDN did not affect the percentage of positive cells, even though the mean fluorescence index was significantly increased (P = 0.0001), thus indicating a higher level of protein production. These data could suggest a possible mechanism of drug resistance after treatment with PDN.

Adolescent↗

PubMed1996

Nuclear translocation of protein kinase C-alpha and -zeta isoforms in HL-60 cells induced to differentiate along the granulocytic lineage by all-trans retinoic acid.

We investigated whether members of the protein kinase C (PKC) family of enzymes were involved in the nuclear events underlying granulocytic differentiation induced by 10(-6) M all-trans retinoic acid (ATRA) in HL-60 cells. PKC activity was analysed by using a serine substituted specific peptide which enabled the evaluation of the whole catalytic activity of both Ca2+ -dependent and Ca2+ -independent PKC isoforms. In parallel, the subcellular distribution of various PKC isoforms was evaluated by Western blot, immunoprecipitation and in situ immunocytochemistry analyses. The level of PKC catalytic activity in the nuclei of HL-60 cells significantly (P < 0.01) and progressively increased from 1 h of ATRA treatment onwards. Consistently, PKC-alpha and -zeta showed a striking and selective accumulation inside the nucleus upon treatment with ATRA. On the other hand, PKC-beta I and -beta II, the only two other isoforms present at nuclear level, did not show any significant modification upon ATRA treatment. The remaining PKC isoforms were not detectable inside the nucleus and showed only modest and non-significant variations, also in whole cell homogenates, upon ATRA treatment, except PKC-delta which showed a progressive down-regulation. Our data suggest that a selective nuclear translocation of PKC-alpha and -zeta might be involved in the process of granulocytic differentiation induced by ATRA in HL-60 cells.

Blotting, Western↗

PubMed1996

Retinoids increase idarubicin cytotoxicity in human myeloid leukemia cell lines.

All-trans-retinoic acid (ATRA) has proven useful in acute promyelocytic leukemia (APL). In order to reduce the side effects and to improve the efficacy of this compound, conventional chemotherapy, and anthracyclines in particular, are frequently added either during remission induction or in consolidation therapy. In this study we aimed at investigating the rationale of the combination of ATRA plus idarubicin in two human leukemic cell lines, HL-60 and K562, that display a different sensitivity to ATRA treatment. The effects of ATRA were compared with those of two clinically active retinoids, 13-cis-retinoic acid (13-cis-RA) and 9-cis-retinoic acid (9-cis-RA). Both in HL-60 and in K562 cells, the majority of the combinations of ATRA and idarubicin were synergistic, while the combinations with 9-cis-RA and 13-cis-RA were more effective in HL-60 and K562 cells, respectively. A 72 h pre-incubation with retinoids was able to further increase the cytotoxicity of ATRA plus idarubicin in the two cell lines. Intracellular idarubicin accumulation was enhanced by retinoids, as demonstrated by a cytofluorimetric method. Our results could contribute to provide a rationale for ATRA plus idarubicin combinations not only in APL but also in acute leukemia of other cytotypes.

Antibiotics, Antineoplastic↗

PubMed1996

FLAG (fludarabine, cytarabine, G-CSF) as a second line therapy for acute lymphoblastic leukemia with myeloid antigen expression: in vitro and in vivo effects.

Thirteen consecutive adult patients with primary refractory (n = 5) or relapsed (n = 8) acute lymphoblastic leukemia (ALL) were treated by an induction schedule (FLAG) consisting of Fludarabine (30 mg/sqm/d) plus high dose Cytarabine (HD-ara-C: 2 g/sqm/d) (d 1-5) and G-CSF (from d O to polymorphonuclear recovery). Patients achieving complete remission (CR) were administered a second FLAG course as consolidation and were then submitted to an individualized program of post-remission therapy, depending on the patient's age and performance status. CR was achieved in 8/12 evaluable cases (67%). The median CR duration was 22.5 w. CR attainment was significantly related to the co-expression of lymphoid and myeloid antigens. ALL/My+ patients achieved CR in 6/6 evaluable cases vs. 2/6 for ALL/My+. In vitro 3H ara-C incorporation into cellular DNA resulted significantly increased by Fludarabine (in 7/9 tested cases) and, furthermore, by the association of Fludarabine G-CSF in 5 evaluable ALL/My+ cases; in contrast, no effect of G-CSF addition to Fludarabine was observed in 4 ALL/My. Myelosuppression was observed in all patients: the median time to neutrophils > 0.5 x 10(9)/1 was 16.3 d (range 13-22) and 16.2 d (range 9-29) to platelets > 20 x 10(9)/1. Nonhematological toxicity was minimal. In conclusion, FLAG is an active and tolerable combination in refractory ALL, particularly in cases with myeloid antigen expression where G-CSF appears to improve efficacy, probably increasing ara-C incorporation into the DNA of leukemic cells.

Adult↗

PubMed1996

Biological and clinical significance of in vitro prednisolone resistance in adult acute lymphoblastic leukaemia.

It has been reported that in vitro prednisolone (PDN) resistance provides a prognostic value in childhood acute lymphoblastic leukaemia (ALL). This study aimed at investigating the biological and clinical significance of in vitro PDN resistance in adult ALL. Blast cells from 30 patients were exposed to PDN (0.1 microM-35 microM) and cytotoxicity was determined by the soluble tetrazolium formazan 2,3-bis (2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenylamino) carbamyl]-2H-tetrazolium hydroxyde (XTT) colorimetric assay. The IC50 (defined as the drug concentration that results in 50% growth inhibition) varied greatly among the samples, from 0.3 microM to > 35 microM; 15 microM was subsequently chosen as IC50-cut-off point between in vitro resistant and sensitive cases. PDN-induced cytotoxicity was significantly related to apoptosis, as demonstrated by regression analysis; in sensitive cases, however, the percentage of apoptotic cells after in vitro PDN treatment was significantly increased compared with control (p = 0.002). Immunofluorescence evaluation of intracellular BCL-2 protein showed an equal percentage of positive cells in the two groups, but in resistant cells a higher mean fluorescence intensity (p = 0.04) was demonstrated. In vitro sensitive and resistant patients did not display differences in clinical characteristics, in cytological, karyotypic and immunophenotypic features and in the outcome of induction therapy. Disease-free survival (DFS), however, was significantly better in sensitive patients (p = 0.02).

Adolescent↗

PubMed1996

All-trans retinoic acid and in vitro cytokine production by acute promyelocytic leukemia cells.

Leukemic cells spontaneously secrete cytokines involved in the proliferation of the clone; in this study we evaluated the effects of all-trans retinoic acid (ATRA) on the in vitro autocrine production of cytokines by acute myeloid leukemia cells. Thirty acute nonlymphoid leukemia cases (ANLL) (10 APL and 20 ANLL of other cytotypes than APL) were studied; the in vitro secretions of IL-1 alpha, IL-3, IL-4, IL-6, IL-10, G-CSF, GM-CSF, TNF-alpha were tested with and without ATRA addition. After 5 d exposure to ATRA 10(-6) M APL-treated samples showed a significant reduction of IL-6 (p = 0.008) and GM-CSF (p = 0.03) and a significant increase of IL-1 alpha (p = 0.01) production, if compared to untreated APL samples. No difference was seen in IL-3, IL-10 and IL-4 productions; G-CSF production resulted absent in all but 3 APL cases, in which addition of ATRA determined increase in the production. Interestingly, the 3 G-CSF-producing cases did not obtain clinical remission with ATRA; GM-CSF and IL-6 were spontaneously produced by all the cases, and 7 of 10 APL patients subsequently obtained complete remission after induction. TNF-alpha was produced only in 1 case. No statistical difference was seen in all the productions obtained from other than promyelocytic acute leukemic cells, both with and without ATRA addition. However, it is noteworthy that the production of IL-6 was more than twice as high in ANLL non-APL than in APL cases. In conclusion, these data could thus suggest possible complementary mechanisms of the exhaustion of the leukemic clone upon treatment with ATRA.

Bone Marrow↗

PubMed1996

Clinical implications of serum levels of soluble CD23 and tumor necrosis factor alpha in low-grade non-Hodgkin's lymphoma.

In the last few years the research for new biological features in low-grade non-Hodgkin's lymphoma has provided important results. Several biological parameters are under evaluation and, in particular, cytokines and soluble receptors levels are showing their importance as prognostic parameters. In the present study, serum levels of tumor necrosis factor alpha (TNF-alpha) and soluble CD23 (sCD23) were measured at the time of diagnosis and after induction polychemotherapy in 40 patients with newly diagnosed low-grade non-Hodgkin's lymphoma (LG-NHL). The treatments were CIOP (cyclophosphamide, idarubicin, vincristine, prednisone) regimen for 28 patients and FMP (fludarabine, mitoxantrone, prednisone) scheme for 12 patients. Pretreatment levels of TNF-alpha were highly elevated in patiets with LG-NHL compared with healthy controls (p = 0.005) and were significantly correlated with the Ann Arbor stage (p = 0.001). sCD23 was detected in 35 patients at diagnosis and were markedly increased in LG-NHL patients when compared to healthy controls (p = 0.005); patients with advanced stage presented higher values than those with early stage disease (p = 0.002). All the complete responders (20/40, 50%) showed a decrease of TNF-alpha and sCD23 levels. By contrast, the combination of high levels of TNF-alpha and sCD23 correspond to a group of non-responders. Our results suggest that TNF-alpha and sCD23 are specific prognostic parameters for LG-NHL, and that they could be used as tumor markers within a potential biological prognostic index.

Adolescent↗

PubMed1996

Combined use of growth factors to stimulate the proliferation of hematopoietic progenitor cells after autologous bone marrow transplantation for lymphoma patients.

We studied the kinetic response and concentration of bone marrow (BM) progenitor cells of patients with lymphoid malignancies submitted to autologous bone marrow transplantation (ABMT), treated with a granulocyte-colony-stimulating factor (G-CSF)/interleukin-3 (IL-3) combination. The results were compared with those of lymphoma patients receiving the same pretransplant conditioning regimen followed by G-CSF alone. Recombinant human (rh)G-CSF was administered as a single subcutaneous (s.c.) injection at the dose of 5 micrograms/kg/day from day + 1 after reinfusion of autologous stem cells, while rhIL-3 was added from day +6 at the dose of 10 micrograms/kg/day s.c. (overlapping schedule). In both groups (i.e. G-CSF- and G-CSF/IL-3-treated patients), cytokine administration was discontinued when the absolute neutrophil count was > 0.5 x 10(9)/l of peripheral blood for 3 consecutive days. Following treatment with the CSF combination, the percentage of marrow CFU-GM and erythroid progenitors (BFU-E) in the S phase of the cell cycle increased from 9.3 +/- 2 to 33.3 +/- 12% and from 14.6 +/- 3 to 35 +/- 6%, respectively (p < 0.05). The number of actively cycling megakaryocyte progenitors (CFU-MK and BFU-MK) also increased. Conversely, G-CSF augmented the proliferative rate of CFU-GM (22.6 +/- 6% compared to a baseline value of 11.5 +/- 3%; p < 0.05) but not of BFU-E, CFU-MK or BFU-MK, and the increase in S-phase CFU-GM was significantly lower than that observed in the posttreatment samples of patients receiving IL-3 in addition to G-CSF. The absolute number of both CFU-GM and BFU-E/ml of BM was significantly augmented after treatment with G-CSF/IL-3 but not G-CSF alone. Similarly, administration of the cytokine combination resulted in a higher number of CD34+ cells and their concentration was significantly greater than that observed in the posttreatment samples of G-CSF patients. We also investigated the responsiveness to CSFs, in vitro, of highly enriched CD34+ cells, collected after priming with G-CSF in vivo (i.e. after 5 days of G-CSF administration). Our results demonstrated that pretreatment with G-CSF modified the response of BM cells to subsequent stimulation with additional CSFs. When the hematological reconstitution of patients treated with G-CSF/ IL-3 was compared to that of individuals receiving G-CSF alone, the addition of IL-3 resulted in a significant improvement in granulocyte and platelet recovery, a lower transfusion requirement and shorted hospitalization. In conclusion, our results indicate that in vivo administration of two cytokines increases the proliferative our results indicate that in vivo administration of two cytokines increase the proliferative our results rate and concentration of BM progenitor cells better than G-CSF alone and support a role for growth factor combinations for accelerating hematopoietic recovery after high-dose chemotherapy.

Antigens, CD34↗

PubMed1996

Concomitant and sequential administration of recombinant human granulocyte colony-stimulating factor and recombinant human interleukin-3 to accelerate hematopoietic recovery after autologous bone marrow transplantation for malignant lymphoma.

PURPOSE: To assess the safety, tolerability, and hematopoietic efficacy of sequential and concomitant administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human interleukin-3 (rhIL-3), to accelerate reconstitution of hematopoiesis following myeloablative chemotherapy and autologous bone marrow transplantation (ABMT) for heavily pretreated lymphoma patients. PATIENTS AND METHODS: Fifty-four consecutive patients with refractory or relapsed non-Hodgkin's lymphoma (NHL; n = 30) and Hodgkin's disease (HD; n = 24) were studied. Two different conditioning regimens were used for ABMT: carmustine, cyclophosphamide, etoposide, and cytarabine (BAVC) and carmustine, melphalan, etoposide, and cytarabine (BEAM) for NHL and HD, respectively. Patients were enrolled sequentially onto one of three treatment groups: group 1, G-CSF (5 micrograms/kg/d subcutaneously [SC]) from day +1 after reinfusion of autologous marrow (n = 23); group 2, G-CSF from day +1 combined with IL-3 (10 micrograms/kg/d SC) from day +6 (n = 22, overlapping schedule); and group 3, G-CSF treatment discontinued at day +6 before initiation of IL-3 administration (n = 9, sequential schedule). In the three groups, growth factor(s) was administered until the granulocyte count was greater than 0.5 x 10(9)/L for 3 consecutive days. RESULTS: The study cytokines were generally well tolerated. No side effects were observed when G-CSF was given alone. Four of 31 patients (12.9%) who received SC IL-3 had one severe adverse event defined as World Health Organization (WHO) grade 3 to 4 toxicity (fever, n = 2; pulmonary toxicity, n = 2) and were withdrawn from the study. Groups 2 and 3 did not differ as for treatment tolerability, whereas we observed a trend toward a faster hematopoietic recovery when IL-3 was administered concomitant with G-CSF from day 6 (ie, group 2). Pooled together, patients who received IL-3 showed a median time to achieve a granulocyte count greater than 0.1 and greater than 0.5 x 10(9)/L of 8 and 11 days, respectively. The median time to an unsupported platelet count greater than 20 and 50 x 10(9)/L was 15 and 20 days, respectively, and only one patient did not reach a normal platelet count. The median number of days to hospital discharge was 16 after ABMT (range, 12 to 29). When the hematologic reconstitution of patients in groups 2 and 3 was compared with that of patients in group 1, the addition of IL-3 resulted in a significant improvement of multilineage hematopoietic recovery, lower transfusion requirements, a lower number of documented infections, and shorter hospitalizations. CONCLUSION: We conclude that the combination of G-CSF and IL-3 is safe and well tolerated in intensively pretreated lymphoma patients, undergoing ABMT and results in rapid hematopoietic recovery following myeloablative chemotherapy.

Adolescent↗

PubMed1996

FLANG (fludarabine + cytosine arabinoside + novantrone + G-CSF) induces partial remission in lymphoid blast transformation of Ph+chronic myelogenous leukaemia.

The adenine nucleoside analogue, fludarabine phosphate, in combination with cytosine-arabinoside (Ara-C) and granulocyte-colony stimulating factor (G-CSF) (the so called FLAG regimen) has recently been shown to be effective in the treatment of poor-prognosis acute non-lymphoid leukaemia. We used this combination plus novantrone (FLANG regimen) in a case of Ph1+ chronic myeloid leukaemia (CML) unresponsive to interferon alpha that had progressed to an acute phase, after 3 months of treatment with 6-mercaptopurine and hydroxyurea. The patient was treated with two courses of fludarabine 30 mg/m2 (days 1-5) + Ara-C 2 g/m2 (days 1-5) + novantrone 5 mg/m2 (days 1-3) and G-CSF from day 0 to neutrophil recovery. After the first cycle of chemotherapy, bone marrow blasts decreased from 100% to less than 5% (clinical complete remission), with a progressive clearance of Ph1+ metaphases (from 100% to 12%). At the end of the second course, a progressive increase of blasts was observed again and karyotypic detection of Ph+ cells was also documented (from 12% to 42.9%). During this partial remission, the patient underwent an allogeneic bone marrow transplantation from an HLA matched identical brother. At the time of this report, he is still alive and well and in complete karyotypic remission. This partial therapeutic success was compared with the result obtained in another previously reported CML case: differences in the therapeutic efficacy of protocols employing fludarabine nucleosides and the type of blastic cells involved are discussed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

All-trans-retinoic acid and pseudotumor cerebri.

Pseudotumor cerebri or idiopathic intracranial hypertension is a neurological syndrome characterized by signs and symptoms of intracranial hypertension without clinical and radiological evidence of infective or space occupying lesions. Iatrogenic factors are frequent; in particular, cases of Pseudotumor cerebri associated with all-trans-retinoic acid treatment in acute promyelocytic leukemia (APL) have been frequently described in pediatric patients. We review the literature and give diagnostic and therapeutic guidelines.

Humans↗

PubMed1996

Adult lymphoblastic lymphoma: clinical features and prognostic factors in 53 patients.

Lymphoblastic lymphoma (LBL) in adult patients is recognized as a particular entity in the high-grade non-Hodgkin's lymphoma (HG-NHL) group with characteristic clinical and prognostic features. Initially, polychemotherapy normally used in HG-NHL failed to produce long-term relapse-free survival because of progression disease in the CNS and in the bone marrow. Subsequently, the intensification of therapy using multimodality aggressive acute lymphoblastic leukemia (ALL) treatments led to an increase in long-term relapse-free survival. We analyzed retrospectively 53 adult patients with LBL according to the Kiel classification and the criteria by Nathwani et al. Therapeutic modifications depended upon the different times of diagnosis. Twenty-one patients received the modified L17 regimen, 13 patients were treated with the L0288 regimen, and 19 patients were submitted to the L20 protocol. There was no significant differences in CR rates among the three protocols: 48% vs 54% vs 63%, respectively. Nineteen of 29 patients who achieved CR were alive and relapse-free at a median follow-up of 84 months. Ten of the CR patients underwent autologous bone marrow transplantation (ABMT) to consolidate the first response and 7 of them are alive and relapse-free. Early stage of disease, age < 30 years, low LDH levels, the absence of leukemic phase at diagnosis, and, in particular the attainment of CR were all features of patients with good prognosis. Our study confirms the role of intensive polychemotherapeutic regimens including CNS prophylaxis, the significance of a score model of prognostic factors, and of the role of ABMT (or allogeneic bone marrow transplantation) in the treatment of adult LBL.

Adolescent↗

PubMed1996

Autologous bone marrow transplantation in late first complete remission improves outcome in acute myelogenous leukemia.

We evaluated the role of ABMT in late 1st CR AML adult patients using busulfan plus cyclophosphamide as preparative regimen. Fifty-one adult patients (mean age 36 years, range 15-59) with AML underwent ABMT in 1st CR. Three of them had a prior diagnosis of myelodysplastic syndrome; one patient had a secondary leukemia. The median interval between CR and ABMT was 8 months (range 4-20). Patients received busulfan, 4 mg/kg/day for 4 days plus cyclophosphamide 50 mg/kg/day for 4 days or 60 mg/kg/day for 2 days. No maintenance chemotherapy was administered after ABMT. Median days to reach 0.5 x 10(9)/I PMN and 20 x 10(9)/I platelets were 26 (range 12-250) and 74 (range 16-740), respectively. No transplant-related deaths were observed. Five-year actuarial overall survival rate is 76.9%; actuarial leukemia-free survival rate is 70.6%. Mean follow-up from ABMT is 35 months. Leukemia-free survival of this group was compared with that of 38 non-transplanted patients younger than 60 years, who maintained a CR longer than 8 months in the same period. This analysis shows a statistically significant difference in favor of ABMT patients. These results suggest that, even if performed late after 1st CR as post-remission intensification, ABMT can improve the outcome of AML patients.

Adolescent↗

PubMed1996

Hepatitis B and C viruses, human T-cell lymphotropic virus types I and II, and leukemias: a case-control study. The Italian Leukemia Study Group.

The relationship between acute myeloid leukemia (AML), acute lymphocytic leukemia, chronic myeloid leukemia (CML), and refractory anemia with excess of blasts (RAEB) and antibodies to human T-cell lymphotropic virus types I and II (HTLV-I and HTLV-II), and hepatitis B virus and hepatitis C virus (HCV) was investigated in a multicenter case-control study. There were 431 cases enrolled in the study at the time of diagnosis of hematological malignancies, and 862 controls ages 15 years or older were recruited in three hospitals. Antibodies to HTLV-I and HTLV-II, antibody to HCV, hepatitis B surface antigen, and antibody to hepatitis B core antigen were assayed. All cases and controls were negative for HTLV-1 antibodies; one case (1 of 431; 0.2%), and one control (1 of 862; 0.1%) were found positive for HTLV-II antibodies. A nonsignificant excess of risk for hepatitis B surface antigen was present among RAEB cases (odds ratio, 2.40; 95% confidence interval, 0.46--12) CML, (odds ratio, 2.70; 95% CI, 0.86--8.43), and between antibody of hepatitis B core antigen and AML (odds ratio, 1.40; 95% CI, 0.93-2.10). A weak, nonsignificant association was present between AML, acute lymphocytic leukemia, RAEB, and antibody to HCV. These preliminary results suggest a possible association (elevated odds ratios) between hepatitis B virus, AML, RAEB, and CML. However, because all confidence intervals overlapped the null value, these findings need to be confirmed in larger case-control studies.

Acute Disease↗

PubMed1996

Detection of occasional and clonal chromosome aberrations in patients with acute non-lymphocytic leukemia after autologous bone marrow transplantation.

Clonal chromosome aberrations observed in patients who have relapsed after autologous bone marrow transplantation (ABMT) are usually related to the cytogenetic abnormalities observed at diagnosis. In order to assess this relationship, we evaluated 30 acute non-lymphocytic leukemia (ANLL) patients who underwent ABMT at out institution and had evaluable serial cytogenetic studies before and after ABMT. Seventeen patients (57%) showed no chromosome aberrations after ABMT in any of the studies performed, while 13 patients (43%) carried abnormalities. In eight out of 30 patients (27%0 the abnormal karyotype after ABMT was associated with hematologic relapse. The cytogenetic abnormalities were: (1) the same as at diagnosis without additional abnormalities in five patients; (2) the same as at diagnosis but with additional abnormalities in three patients. In one patient a different karyotype from that of diagnosis was detected and a myelodysplastic syndrome was clinically evaluable. Furthermore, occasional and single cell chromosome abnormalities were observed in four patients (13%), none of whom relapsed. The new and additional clonal cytogenetic abnormalities observed after ABMT were found in eight patients (27%), suggesting that this event may not be so frequent, that is presumably associated regimen. The re-appearance of the chromosome aberrations after ABMT and the relationship with the risk of relapse are discussed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups.

BACKGROUND: Allogeneic or autologous bone marrow transplantation and intensive consolidation chemotherapy are used to treat acute myelogenous leukemia in a first complete remission. METHODS: After induction treatment with daunorubicin and cytarabine, patients who had a complete remission received a first course of intensive consolidation chemotherapy, combining intermediate-dose cytarabine and amsacrine. Patients with an HLA-identical sibling were assigned to undergo allogeneic bone marrow transplantation; the others were randomly assigned to undergo autologous bone marrow transplantation (with unpurged bone marrow) or a second course of intensive chemotherapy, combining high-dose cytarabine and daunorubicin. Comparisons were made on the basis of the intention to treat. RESULTS: A total of 623 patients had a complete remission; 168 were assigned to undergo allogeneic bone marrow transplantation, and 254 were randomly assigned to one of the other two groups. Of these patients, 343 completed the treatment assignment: 144 in the allogeneic-transplantation group, 95 in the autologous-transplantation group, and 104 in the intensive-chemotherapy group. The relapse rate was highest in the intensive-chemotherapy group and lowest in the allogeneic-transplantation group, whereas the mortality rate was highest after allogeneic transplantation and lowest after intensive chemotherapy. The projected rate of disease-free survival at four years was 55 percent for allogeneic transplantation, 48 percent for autologous transplantation, and 30 percent for intensive chemotherapy. However, the overall survival after complete remission was similar in the three groups, since more patients who relapsed after a second course of intensive chemotherapy had a response to subsequent autologous bone marrow transplantation. Other differences were also observed, especially with regard to hematopoietic recovery (it occurred later after autologous transplantation) and the duration of hospitalization (it was longer with bone marrow transplantation). CONCLUSIONS: Autologous as well as allogeneic bone marrow transplantation results in better disease-free survival than intensive consolidation chemotherapy with high-dose cytarabine and daunorubicin. Transplantation soon after a relapse or during a second complete remission might also be appropriate.

Adolescent↗

PubMed1995

Latent acute promyelocytic leukaemia in a case of ischaemic stroke underlines the importance of prompt diagnostic confirmation prior to acute care.

When treating stroke as a medical emergency, more uncommon causes should be carefully and promptly considered, since timing may be crucial not only to any neuroprotective and particularly thrombolytic therapy but also to the management of an underlying life-threatening disease. This issue is illustrated in the report of an apparently extremely rare case in which an infarction in the territory of the middle cerebral artery was the presenting symptom of acute promyelocytic leukaemia with associated disseminated intravascular coagulation, which we believe highlights the imperative need of immediate haematological tests on all acute stroke patients.

Adult↗