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F Lo Coco

Publications and source records attributed to F Lo Coco.

At least 37 records · Page 2Linked to original sources
PubMed1990

Rearrangements and aberrant expression of the retinoic acid receptor alpha gene in acute promyelocytic leukemias.

Although acute promyelocytic leukemias (APLs) are consistently associated with a reciprocal chromosome 15;17 translocation, the gene(s) directly affected by the breakpoints have never been isolated. The chromosome 17 breakpoint maps to near the retinoic acid receptor alpha (RAR alpha) locus. Investigation of 20 APLs and a large series of other neoplastic patients and normal controls revealed RAR alpha gene rearrangements and aberrant transcripts only in the APL cases. These findings suggest that the RAR alpha gene is involved in the APL chromosome 17 breakpoint, is implicated in leukemogenesis, and could be used as a marker for identifying leukemic promyelocytes.

Blotting, Northern↗
PubMed1990

Alpha-2b-interferon as single therapy for patients with chronic myeloid leukemia relapsing after T-cell depleted allogeneic bone marrow transplantation.

20 CML patients with hematological (5 pts) or only cytogenetic (15 pts) relapse occurring after allogeneic BMT have been treated with alpha-2b-interferon (IFN) at a starting dose of 5 x 10(6) IU/m2, subcutaneously, three times a week. All 5 patients with hematological relapse achieved hematological remission without reduction of bone marrow Ph1-positive cells. With a median follow-up of 43 months (range 6-48) from the hematological relapse, 3 patients are alive and 2 patients died from non-lymphoid blast crisis. 7 out of 15 patients with only cytogenetic relapse remain in hematological remission at a median of 37 months (range 3-45) from cytogenetic relapse, with 2 patients achieving complete cytogenetic remission confirmed at the molecular level by disappearance of the bcr rearranged band. With a median follow-up of 21 months (range 6-46), 8 patients progressed from cytogenetic to hematological relapse: 4 patients died from blast crisis and the other 4 patients are currently alive in chronic phase. For the 15 patients, the actuarial survival from BMT is 71% at 5 years.

Adolescent↗
PubMed1990

Prolonged suppression of myeloid progenitor cell numbers after stopping interferon treatment for CML may necessitate delay in harvesting marrow cells for autografting.

Fourteen patients with chronic myelogenous leukemia in chronic phase who had achieved hematological remission after alpha-interferon (IFN) therapy were evaluated for their ability to form hemopoietic colonies in vitro. Patients were studied both before and after discontinuation of IFN to assess the optimal timing for a further therapeutic approach consisting of stem cell collection followed by autologous bone marrow transplantation (ABMT). Before stopping IFN a profound inhibition of CFU-GM and BFU-E growth was observed. The numbers of CFU-GM and BFU-E in the bone marrow recovered to 50 per 2 x 10(5) cells plated at a median of 158 and 122 days, respectively, after stopping IFN. At that time, 12 patients were submitted to stem cell harvest and subsequently to ABMT. All patients showed complete engraftment and hematological reconstitution; cytogenetic improvement was observed in eight (67%) cases; two patients displayed complete disappearance of the Ph1 chromosome, confirmed at the molecular level. Eleven of the 12 patients are still in hematological remission at a median of 18 months from autografting and a median of 48 months from diagnosis.

Bone Marrow↗
PubMed1990

Therapy-induced Ph1 suppression in chronic myeloid leukemia: molecular and cytogenetic studies in patients treated with alpha-2b IFN, high-dose chemotherapy and autologous stem cell infusion.

In this study, cytogenetic and molecular analyses were employed to assess the response to therapy in 29 chronic myeloid leukemia patients undergoing high dose chemotherapy followed by autologous stem cell infusion. Of these, 11 had previously achieved hematologic remission and cytogenetic improvement after alpha-2b interferon (IFN) treatment, whereas 18 underwent autografting in an early phase of the disease. In each case bone marrow samples were examined pre-treatment and at +2, +6 and +12 months in order to verify the degree of Ph1 suppression. In addition, the position of the breakpoint within the BCR region was mapped with multiple restriction enzymes. In 17 cases (59%) a significant Ph1 reduction was observed at +60 days (0-57% residual Ph1+ cells). In three of these cases, a complete cytogenetic response was confirmed at the DNA level by Southern blotting, but specific amplification of the BCR/ABL junction by the polymerase chain reaction (PCR), performed in two cases, still showed residual disease. The remaining 12 patients (41%) revealed a substantial persistence of Ph1+ metaphases (90-100%). Nine of 17 responding patients (53%) showed an increase of Ph1+ cells at 6 months, and five of 20 evaluated had a further increase at 12 months. With the exception of the results seen by PCR, comparison of molecular and cytogenetic techniques did not show significant differences. The variable degrees of Ph1 suppression observed did not appear to be associated with the position of BCR breakpoints. The factors predicting cytogenetic response to IFN and stem cell autograft and long-term durability of cytoconversion should be elucidated in further studies and with longer follow-up.

Base Sequence↗
PubMed1990

Interferon therapy for Ph1 positive CML patients relapsing after T cell-depleted allogeneic bone marrow transplantation.

Eighteen chronic myeloid leukemia patients with hematological (four patients) or only cytogenetic (14 patients) relapse occurring after T cell-depleted allogeneic bone marrow transplantation (BMT) have been treated with alpha 2b interferon (IFN) at a starting dose of 5 x 10(6) i.u./m2 subcutaneously three times a week. All four patients with hematological relapse achieved long-lasting hematological remission without reduction of bone marrow Ph1 positive cells. When IFN was started the median percentage of bone marrow Ph1-positive metaphases was 50% (range 9-100) for the 14 patients with cytogenetic relapse. Twelve (85.7%) of these patients are alive with a median follow-up of 25 months (range 20-37 months) from cytogenetic relapse and 33 months (range 27-49 months) from BMT. Six (43%) of the 14 patients progressed to hematological relapse and eight patients (57%) are still in hematological remission with two patients achieving complete cytogenetic remission confirmed at molecular level by disappearance of the M-BCR rearranged band. IFN therapy may be a good alternative to conventional chemotherapy for transplanted CML patients with hematological relapse and the treatment of choice for patients with a persistent cytogenetic relapse occurring after T cell-depleted BMT.

Adolescent↗
PubMed1989

Immunophenotyping of acute myeloid leukaemia: relevance of analysing different lineage-associated markers.

The immunophenotype of 135 previously untreated patients with FAB defined acute myeloid leukaemia (AML) was studied at diagnosis. The panel of reagents included monoclonal antibodies (MoAb) recognising myeloid-associated determinants (CD11, CD13, CD14, CD33 and others) as well as MoAb directed towards lymphoid antigens (CD7, CD10, CD19) and TdT. The results indicate that CD13 and/or CD33 are consistently expressed in AML and only rarely in ALL blasts (131/135 + ve cases, versus 4/130 in ALL). Lymphoid antigen expression was rarely detected when CD10 and CD19 were investigated in AML (0.9% and 2% + ve cases, respectively), whereas significant positivities were found for TdT and CD7 (20% and 10% respectively). Concerning FAB subtypes, two new MoAb (LAM3 and LAM7) proved very useful in the specific recognition of AML with monocytic features. The phenotype CD13+ and/or CD33+, CD9+, HLA-DR- was found to be almost exclusive for M3 AML. The response to induction chemotherapy was analysed in CD7+ and in TdT+ patients. In the latter group a statistically significant lower response rate was found with respect to TdT-ve-AML patients.

Adolescent↗
PubMed1989

Molecular characterization of Ph' + hybrid acute leukemia.

The configuration of the immunoglobulin heavy chain (IgH), T-cell receptor (TcR) beta and gamma chain regions, and the major breakpoint cluster region (M-bcr) genes were analysed in four cases of Ph' + acute leukemia (AL). Monoclonal rearrangements of the IgH region were detected in three cases exhibiting two phenotypically distinct cell populations (i.e. one lymphoid and one myeloid. In one of these cases, identical genetic events were observed by molecular analysis of FACS separated blasts. Multi-lineage rearrangements involving also the TcR gamma gene were observed in a biphenotypic AL showing co-expression of markers. The lack of rearrangements within the M-bcr gene, together with demonstration in one case of the Ph' + AL specific p190 protein product, pointed against the occurrence of chronic myeloid leukemias presenting in blastic transformation. Our results imply that such cases are to be considered as true AL and should therefore be included in the definition of hybrid AL.

Acute Disease↗
PubMed1989

CD7 positive acute myeloid leukaemia: a subtype associated with cell immaturity.

Seventeen patients with acute myeloid leukaemia (AML) whose blasts co-expressed the T-cell associated CD7 antibody were identified among 160 consecutive AML cases. Fourteen had FAB defined AML according to morphocytochemical criteria, whereas three patients were classified as 'MO' on the basis of immunophenotype. The incidence of CD7 positively was particularly significant in the less differentiated subtypes M0 and M1 compared with other FAB groups (P less than 0.001). In all cases the myeloid determinants CD13 and/or CD33 were associated with CD7 expression. Other B-lymphoid (CD10, CD19) or T-lymphoid (CD2, surface and cytoplasmic CD3) markers were analysed and found to be negative. Five out of 15 cases examined were TdT+. Clonal rearrangements of the immunoglobulin heavy chain (IgH) and/or T-cell receptor (TcR) beta chain genes were identified in only three out of 13 cases. Among these, one out of five co-expressing TdT showed IgH rearrangement when analysed at the DNA level. Clinical features at presentation and response to induction therapy did not allow us to consider CD7+ AML patients as a distinct subgroup with prognostic significance. Our data indicate that CD7 expression is a common finding in immature AML, being generally found in the absence of other T-cell features. Rather than suggesting the occurrence of 'mixed leukaemia', such cases confirm a broader spectrum of CD7 reactivity and its possible identification of a particular subset of myeloid progenitors.

Antigens, CD7↗
PubMed1989

Autologous bone marrow or peripheral blood stem cell transplantation for patients with chronic myelogenous leukaemia in chronic phase.

The progressive and fatal course of chronic myelogenous leukemia has not been affected significantly by chemotherapeutic agents that control the benign phase of the disease. Combination chemotherapy and aggressive treatments may offer some advantages: however, these approaches do not appear to produce stable suppression of Ph1 chromosome or to prolong chronic phase and survival of these patients. Only allogeneic bone marrow transplantation has been demonstrated to be capable of inducing a stable, complete suppression of Ph1+ cells. Recently alpha Interferons (IFN) have been shown to control myeloid proliferation in patients with CML and to determine a progressive and persistent decline of Ph1+ bone marrow cells in some cases. The hypothesis that in most newly diagnosed patients with CML various amount of Ph1 negative cells must still be present, albeit in suppressed state in the bone marrow (BM) or in the peripheral blood (PB), have led some Authors to treat patients with high-dose chemotherapy followed by reinfusion of stem cells collected at diagnosis or after a response to cytoreductive treatments. We report 34 patients with CML treated in chronic phase with Busulohan and Melphalan conditioning regimen followed by reinfusion of BM or PB stem cells.

Adult↗
PubMed1989

Ontogeny, gene rearrangements and immunophenotype of acute leukaemias.

The progressive availability of more sophisticated technologies has over the last few years allowed a more precise definition of the biological properties of acute leukaemia cells. This, in turn, has enabled to recognize the ontogeny of practically all cases, with particular emphasis to acute lymphoblastic leukaemia, the lineage affiliation of which had, for many years remained uncertain in over half of the cases. Here, we shall review the main achievements, obtained with extensive immunotyping coupled to the use of probes for the immunoglobulin and T-cell receptor genes, which have led to these important clinico-biological acquisitions, and discuss specific situations in which this combined phenotypic and genotypic approach (as well as response to cloned growth factors) may be of particular value.

Antigens, Differentiation↗
PubMed1989

Acute lymphoblastic leukemia with the 4;11 translocation exhibiting early T cell features.

We describe a case of ALL with the t(4;11) (q21;q23) translocation in which both surface markers and molecular analyses suggest an unusual early T cell involvement. While the morphologic and cytochemical studies showed an undifferentiated pattern, immunophenotypic data were suggestive of a very immature cell population which stained only for TdT and CD7. Moreover, in contrast to previous reports but in agreement with the immunologic findings, the IgH gene region retained a germline configuration. T cell receptor beta and gamma chain gene loci also showed a germline pattern, in accordance with the expansion of immature CD7+, TdT+ T cells.

Adult↗
PubMed1988

Immune-deficiency in Hodgkin's disease (HD): a study of patients and healthy relatives in families with multiple cases.

In this study we evaluated some immunological features in both patients and healthy relatives within five families with multiple cases of Hodgkin's disease (HD). Such familial groups (at 'high risk' of HD), represent, in our opinion, a suitable opportunity to investigate the role of immune-deficiency in HD. The results obtained in the patient group confirm the well known persistent immune derangement in long term HD survivors. Regarding the group of relatives, we found a pattern similar to that of the patients. In particular, a decrease in the T helper lymphocyte subset and a lower response to Con-A mitogen were detected, which were statistically significant. These findings, confirmed in other studies of multiple case families, could support the hypothesis of a preexisting immune-deficiency in HD. This in turn would greatly contribute towards a better understanding of the role of immune-deficiency in the etiopathogenesis of the disease.

Adolescent↗
PubMed1987

Secondary acute non lymphoid leukemia in patients treated for non Hodgkin's lymphoma: no risk of therapy-related ANLL after PROVECIP schedule.

The present study was undertaken to evaluate the frequency, characteristics and actuarial risk of secondary acute non lymphoid leukemia (s-ANLL) in 141 patients treated for non Hodgkin's lymphoma with different modalities. One hundred and twenty-four patients received chemotherapy according to PROVECIP protocol. Of these, 15 also received as induction treatment a local nodal irradiation and 33 an extended field radiotherapy. Seventeen out of 141 were treated by total body irradiation. Of these, 15 relapsed and received salvage chemotherapy. Sixteen of the 124 patients treated with PROVECIP also underwent different chemotherapeutic programs as salvage treatment. Of the entire population studied, 2 patients developed an s-ANLL, 45 and 63 months after diagnosis of NHL. The type of treatment significantly affected the occurrence of s-ANLL, since both leukemias occurred in patients treated with total body irradiation, given alone or followed by chemotherapy. The actuarial risk at 8 years was 5.24% in the whole group, whereas it greatly increased in the group of patients treated with total body irradiation (24%). Conversely, no risk was found in the group treated with PROVECIP, alone, with additional chemotherapy, or with associated local or extended field radiotherapy.

Acute Disease↗
PubMed1987

CALLA-negative, TdT- and CD7-positive acute lymphoblastic leukemia: a phenotype associated with poor prognosis.

Eight ALL patients displaying a CD7+, Tdt+, CD10-, T MoAbs-, myeloid MoAbs-, AP+ phenotype are described. Some patients showed well-known risk factors such as cytogenetic abnormalities, high WBC count, mediastinal mass, and/or organomegalies. The clinical behaviour was very poor and only one patient is in CR and off therapy. Therefore such a pre-T phenotype, although sometimes associated with the other risk factors, could be considered a poor prognosis phenotype.

Adolescent↗
PubMedDate not supplied

Terminal transferase positive acute myeloid leukemia: immunophenotypic characterization and response to induction therapy.

A quantitative evaluation of terminal deoxynucleotidyl transferase (TdT) was performed using a highly sensitive enzyme immunoassay (EIA) in 72 previously untreated patients with acute myeloid leukemia (AML). Biological analysis of the leukemic cells included in all cases cytochemistry, search for Ph' chromosome and immunophenotyping with both anti-lymphoid and anti-myeloid monoclonal antibodies (MoAbs). Thirteen AML cases (18 per cent) were considered TdT+ by EIA. According to the FAB classification, almost all of them (12 out of 13) were within the M1 and M2 subgroups. A mixed lymphoid-myeloid phenotype was observed in one of the 13 TdT+ cases, while in none of the others were lymphoid features detected. Nine of the 10 EIA TdT+ cases studied in parallel were TdT positive with the conventional immunofluorescence assay. All patients received standard protocol chemotherapy and in 61 (13 TdT+, 48 TdT--) the response to induction treatment was analysable. Only 3/13 TdT+ patients (23 per cent) achieved a complete remission (CR), while in the TdT- group 38 patients had a CR (79 per cent) and 10 were resistant (p less than 0.01). It is suggested that the incidence, biological interest and prognostic significance of TdT+ AML should encourage the routine and more accurate search for this marker in all patients with AML.

Adolescent↗
PubMedDate not supplied

Molecular diagnosis of Philadelphia chromosome-positive chronic myeloid leukemia.

BACKGROUND: In virtually all Ph1 chromosome-positive CML patients, the breakpoint on chromosome 22 maps in a very restricted area of 5.8 Kb, which has been named "breakpoint cluster region" or "bcr". Several molecular probes of this region are presently available, and this makes the molecular diagnosis of CML a useful approach which can be particularly important in those cases in which cytogenetic analysis does not reveal the presence of a Ph1 chromosome. Here we report the problems and our experience during the molecular analysis of the 478 patients examined so far. METHODS: Molecular analyses were performed after digestion of the DNA with 2 to 4 restriction enzymes and hybridization with different probes. Individual samples were subjected to PCR since no rearrangements had been obtained with Southern blotting. RESULTS: Rearrangement bands were detected in all the samples examined. In 473 cases the breakpoint was located within the bcr. In one of these cases, it was detected only after PCR analysis, and in two cases only after the use of the PHL/BCR probe. In 5 cases the breakpoint was localized either 5' or 3' with respect to the bcr. CONCLUSIONS: In this paper, the criteria for a correct molecular diagnosis of CML are presented. The "PHL/BCR" probe appeared to be very specific and time-saving, since it required only one digestion to evidence the rearrangement. Our results confirm the high specificity of the breakpoint on chromosome 22 in CML and the relatively rare incidence of molecular variants.

Base Sequence↗