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Biomedical subjects

M F Martelli

Publications and source records attributed to M F Martelli.

At least 91 records · Page 5Linked to original sources
PubMed1992

Interstitial pneumonitis after hyperfractionated total body irradiation in HLA-matched T-depleted bone marrow transplantation.

Interstitial pneumonia is one of the major causes of morbidity and mortality after bone-marrow transplantation. We here report a series of 58 patients suffering from hematological malignancies who received HLA-matched T-lymphocyte depleted bone-marrow transplants between July 1985 and January 1990. Interstitial pneumonia occurred in 7/58 patients (12%) and was fatal in six. Three different pre-bone-marrow transplantation conditioning regimens were employed. Total body irradiation was delivered according to a hyperfractionated scheme of 12 fractions given three per day 5 hr apart for 4 days. Twenty-three patients received 36 mg/Kg procarbazine, 1275 UL/Kg antithymocite globulin, 14.4 Gy hyperfractionated total body irradiation and 120 mg/Kg cyclophosphamide. Only one patient developed interstitial pneumonia, but two rejected the graft and 10 relapsed. As a consequence, the total hyperfractionated scheme was increased to 15,6 Gy, cyclophosphamide to 200 mg/Kg, antithymocite globulin to 3400 UL/Kg and procarbazine eliminated. There were three cases of interstitial pneumonia, no rejection and four relapses in the 17 patients who received this regimen. In the last 18 patients hyperfractionated total body irradiation was reduced to 15 Gy, cyclophosphamide to 100 mg/Kg, and 10 mg/Kg of the myeloablative agent thiothepa added to enhance the cytoreductive effect without significantly increasing extramedullary toxicity. Three cases of interstitial pneumonia, one relapse but no rejection were recorded. Our results demonstrate that the absence of graft-versus-host disease due to T-cell depletion, and radio-chemotherapy doses and schedules used for the conditioning regimen each contributed to reducing the risk of interstitial pneumonitis. Hyperfractionated total body irradiation therefore, seems to play an important role in lowering the incidence of this complication.

Adolescent↗
PubMed1991

Interferon alpha-2b in the long-term treatment of essential thrombocythemia.

We treated 35 patients affected with essential thrombocythemia (ET) with interferon (IFN) alpha-2b. Our treatment scheme consisted of (a) a 6-month induction phase and (b) a continuous maintenance phase. During the induction phase, our results showed that using 21 million units (mu) of IFN weekly platelet counts fell below 600 x 10(9)/1 in about 90% of patients. These data demonstrate that well-tolerated doses of IFN can rapidly correct excessive thrombocytosis. During the continuous maintenance phase, 61% of patients required 3 mu three times a week, 15% once a week, and 24% daily. Thus the minimal IFN doses able to maintain platelet count below 600 x 10(9)/l varied between 3 and 21 mu per week. During long-term treatment, subjective side effects were tolerable, especially using 3 mu three times a week. We conclude that IFN alpha-2b is an effective drug in the long-term treatment of ET.

Adult↗
PubMed1991

Activation of the granulocyte-monocyte colony stimulating factor gene in acute myeloid leukaemia cells is not related to gene rearrangement.

Several reports have documented that leukaemic blasts produce a number of cytokines among them the granulocyte-monocyte colony stimulating factor (GM-CSF). We analysed the structure of the gene that codes for GM-CSF in 44 acute myeloid leukaemia (AML) cases in an attempt to establish whether the autocrine production of GM-CSF was due to a structural gene alteration. No structural alteration was detected in the GM-CSF gene in any of the 44 cases studied. We, therefore, conclude that the autocrine production of GM-CSF by leukaemia blasts is not dependent on gene rearrangement.

Gene Expression Regulation, Neoplastic↗
PubMed1991

Lung damage following bone marrow transplantation after hyperfractionated total body irradiation.

From July 1985 to December 1989, 72 evaluable patients aged between 6 and 51 (median age 27 years) suffering from haematological malignancies received an allogeneic bone marrow transplant (BMT) depleted of T-lymphocytes to reduce the risk of graft-versus-host-disease (GvHD); 57 were matched and 15 mismatched. Three different conditioning regimens were used in an effort to enhance cytoreduction without increase extramedullary toxicity. Mismatched patients were treated with more immunosuppressive regimens. Total body irradiation (TBI) was given in three doses per day, 5 h apart, over 4 days for a total of 12 fractions. The dose to the lungs was 14.4, 15.6 and 9 Gy according to the conditioning regimen. The incidence of interstitial pneumonia (IP) was 12.3% in matched and 46.7% in mismatched patients. Our results seem to indicate that lung toxicity is correlated with the intensity of the conditioning regimen, the stage of disease and, in mismatched patients, with the degree of human leucocyte antigen (HLA) disparity and the poor post-BMT reconstitution, rather than the radiotherapy dose delivered to the lungs. On the contrary, the hyperfractionated scheme adopted, the absence of GvHD and, perhaps, the post-TBI administration of cyclophosphamide all seem to have contributed to the low incidence of IP in our matched patients.

Adolescent↗
PubMed1991

Expression of the intestinal T-lymphocyte associated molecule HML-1: analysis of 75 non-Hodgkin's lymphomas and description of the first HML-1 positive T-lymphoblastic tumour.

The expression of the gut intra-epithelial T-cell associated molecule HML-1, a trimeric protein of 150, 125, 105 kD, was studied in 75 T-cell lymphomas of different subtypes: 20 T-lymphoblastic lymphomas/leukaemias; 50 nodal peripheral T-cell lymphomas; and five intestinal T-cell lymphomas. Our results confirm: (i) the usefulness of the HML-1 monoclonal antibody as an immunohistochemical marker for intestinal T-cell lymphomas: and (ii) the lack of reactivity of HML-1 with nodal peripheral T-cell lymphomas. Moreover, expression of the HML-1 molecule was found for the first time in a case of T-lymphoblastic lymphoma/leukaemia. The patient presented with a mediastinal mass which consisted of HML-1 + neoplastic cells displaying a phenotypic profile consistent with early thymocytes. Genes coding for the alpha, beta, gamma and delta chains of the T-cell receptor were in a germline configuration. The neoplastic cells could have been derived from the small subset of HML-1 + thymocytes detectable in the cortex of normal human thymus.

Adolescent↗
PubMed1990

Cytolytic function of clonable T cells after human bone marrow transplantation.

We evaluated T-cell mediated lymphokine activated killer (LAK) function during the late (greater than 5 months) reconstitution phase after T cell-depleted allogeneic bone marrow transplantation (BMT) for hematologic malignancy. Since LAK cells are sustained by interleukin-2 (IL-2), we also investigated the ability of post-BMT T cells to produce IL-2. These functions were investigated at the clonal level. More than 200 T-cell clones from six long-term BMT recipients were generated and compared with 60 T-cell clones derived from two normal controls. Almost all the CD8+ clonal cultures from BMT recipients expressed cytolytic activity in a lectin-dependent cellular cytoxicity assay. Interestingly, a higher proportion of BMT recipient-derived cytolytic clones were able to mediate LAK activity in comparison with control clones (28% versus 4%, P less than .05). However, T-cell clones from BMT recipients, as opposed to control clones, were largely incapable of producing IL-2. Given the high proportions of post-BMT circulating CD8+ T cells, it appears that, in long-term BMT recipients, the precursors of nonspecific LAK effectors are present at above normal levels. However, their function may be defective in vivo due to poor IL-2 production.

Bone Marrow Transplantation↗
PubMed1990

Peripheral T-cell lymphoma associated with hemophagocytic syndrome.

Nine patients with an acute disease characterized by high fever, loss of weight, prominent hepatosplenomegaly, slight or no lymphadenopathy, abnormal liver function tests, and profound pancytopenia are reported. In all cases, the disease presented in the absence of any pre-existing disease or immunosuppressive therapy. In seven of the nine patients, survival was very short (mean = 7 weeks). Two patients are still alive: one had a relapse 24 months after the initial diagnosis, while the other is in complete remission. The main pathological feature was the infiltration of the marrow, spleen and liver by neoplastic T cells, accompanied by an exuberant hyperplasia of benign-looking, hemophagocytizing histiocytes. The term "peripheral T-cell lymphoma with hemophagocytic syndrome" is proposed for this condition. Retrospective analysis of stored paraffin material (1949 to 1965) from the Radcliffe Infirmary files suggests that at least some of the cases designated as "histiocytic medullary reticulosis" by Scott and Robb-Smith were examples of the syndrome herein described.

Autopsy↗
PubMed1990

Antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation.

Allogeneic bone marrow-engrafted adults immunized with meningococcal types A and C and pneumococcal type 14 polysaccharide antigens showed only low antibody titers of the IgM class, no antibody titers of the IgG or IgA classes, and no bactericidal activity in vitro. The analytical isoelectrofocusing showed the appearance of a restricted pattern of clonotypes in a minority of subjects. These observations are consistent with the hypothesis that B cells in bone marrow transplant patients express some characteristics of neonatal B cells and suggest that polysaccharide-protein conjugates, rather than isolated polysaccharide, might be utilized in the setting of bone marrow transplantation.

Adult↗
PubMed1990

Response to intermediate and standard doses of IFN-beta in hairy-cell leukaemia.

Thirteen hairy-cell leukaemia patients were treated with IFN-beta (6 X 10(6) IU/m2) for 7 days, alternate weeks, for three cycles. IFN-beta was then continued at the same dose twice a week for 24 weeks. Treatment was discontinued in 2 non-responders and 2 partial responders (1 haem PR, 1 path PR) because of complications unrelated to IFN. The objective response in the nine patients who completed therapy was 66% (1 CR, 3 path PR and 2 haem PR); 2 patients achieved MR. Responses lasted from 5 to 45+ months. Four newly diagnosed patients and 3 in relapse after discontinuation of IFN-beta therapy (6 X 10(6) IU/m2), were treated with a lower dose of IFN-beta (2 X 10(6) IU/m2). The objective response to this dose was 57% (3 path PR, 1 haem PR). Another patient obtained MR. No patient has relapsed 6-12 months after therapy discontinuation. IFN-beta was well tolerated, especially at the lower dose and no chronic toxicity was observed. Therefore IFN-beta may be suggested as an alternative treatment for HCL.

Adult↗
PubMed1990

Partial trisomy 1q in idiopathic myelofibrosis.

Three cases of idiopathic myelofibrosis with partial trisomy of the long arm of chromosome 1 are described. Partial trisomy 1q was the only karyotypic change detectable in unstimulated peripheral blood cell cultures of one and bone-marrow cultures of two patients at diagnosis. The extra segment from chromosome 1 was located on different karyotype sites, i.e. 1qter, 1p34 and 6p22-23; 1q21-32 was the shortest overlapping region and the only trisomic segment in one of the three patients. These findings suggest that partial trisomy 1q is a primary chromosome aberration in myelofibrosis relevant in the pathogenesis of this hematologic disorder.

Aged↗
PubMed1990

Variable expression of leucocyte-common (CD45) antigen in CD30 (Ki1)-positive anaplastic large-cell lymphoma: implications for the differential diagnosis between lymphoid and nonlymphoid malignancies.

Monoclonal antibodies (mAbs) directed against the leucocyte common (CD45) antigen have been proposed as a useful tool for the differential diagnosis between malignant lymphomas (CD45+) and poorly differentiated nonhemopoietic tumors (CD45-). Thanks to the availability of mAbs directed against fixative-resistant epitopes of the CD45 molecule, this distinction can now easily be made even in routinely processed tissues. However, a small percentage of morphologically poorly defined neoplasms are difficult to diagnose even with the help of immunohistochemistry. The investigators report that 63 out of 165 anaplastic large-cell (ALC) lymphomas did not show any reactivity for the CD45 antigen in paraffin sections. In routine biopsies, the lymphomatous nature of these cases, most of which had been sent for consultation, could be always unequivocally established by demonstrating negativity for cytokeratins (mAb KL1) and clear dot-like and/or surface reactivity with the Ber-H2 mAb, which is directed against a fixative-resistant epitope of the lymphoid cell activation antigen CD30. Strikingly, 54% of the CD45-cases reacted with mAbs directed against fixative-resistant epitopes of the T cell-restricted CD45RO antigen (mAb UCHL1) or the B-restricted molecules CD45RA (mAb 4KB5) and L26 (unclustered). In order to avoid confusion of ALC lymphomas with anaplastic nonlymphoid tumors, pathologists must be aware of the existence of CD30+/CD45- ALC lymphomas, as they can mimic the above-mentioned malignancies both morphologically (due to the sinusoidal growth pattern) and phenotypically (due to the expression of EMA). The investigators conclude that the combined use of mAbs directed against fixative-resistant epitopes of the CD30, CD45RO, CD45RA, and L26 antigens and cytokeratins is essential for the correct diagnosis and treatment of these equivocal cases.

Antibodies, Monoclonal↗
PubMed1990

Selection of a panel of monoclonal antibodies for monitoring residual disease in peripheral blood and bone marrow of interferon-treated hairy cell leukaemia patients.

A panel of monoclonal antibodies (mAbs) directed against B-cell and hairy cell leukaemia (HCL)-associated antigens was used to identify residual hairy cells in the peripheral blood and/or bone marrow samples from 20 patients with HCL, following treatment with interferon-alpha (IFN-alpha) or interferon-beta (IFN-beta). In all cases, hairy cells retained their characteristic phenotype, e.g. positivity for CD22, CD11c, CD25, CD32, and the HCL-associated trimeric protein (t-GP) recognized by the mAbs HML-1, B-ly7, LF61 and Ber-Act8. The most specific marker for identifying a small percentage of hairy cells in peripheral blood cytospins, was t-GP. In alkaline phosphatase/anti alkaline phosphatase (APAAP) stained preparations, t-GP+ hairy cells (provided with large cytoplasm and hairy surface) could be usually distinguished from t-GP+ normal lymphocytes (small-sized cells with smooth surface). In doubtful cases the percentage of residual hairy cells could exactly be estimated by double immunofluorescence staining for CD22 (B-cell marker) and t-GP. The rationale of the test is based on the finding that the small percentage (about 1%) of t-GP+ lymphocytes circulating in the peripheral blood of normal individuals are T-cells of the CD8 subset and not B-cells. The best markers for identifying residual hairy cells in routine bone marrow biopsies were CD45RA (mAb 4KB5) and CD20 (mAb L26). Immunohistological labelling was superior to morphological examination in picking up scattered hairy cells in bone marrow biopsies showing either severe hypoplasia or exuberant hyperplasia of normal haemopoietic series.

Antibodies, Monoclonal↗
PubMed1990

Lymphohistiocytic T-cell lymphoma (anaplastic large cell lymphoma CD30+/Ki-1 + with a high content of reactive histiocytes).

We describe 13 cases of a peculiar lymphoid tumour containing very large numbers of reactive histiocytes. The tumours occurred in young patients (mean age 14.8 y) who presented with systemic symptoms and superficial lymphadenopathy. Microscopic examination revealed a diffuse effacement of lymph node structure due to the presence of histiocytes intermingled with a variable number of anaplastic large lymphoid cells. The latter, in some cases, were isolated, while in others they were arranged in clusters or were diffusely present in residual sinuses. The large anaplastic cells expressed the activation markers CD30 (Ki-1), CD25 (interleukin-2 receptor), CD70 (Ki-24) and Ki-27, as well as varying combinations of T-associated molecules. The histiocytes expressed lysozyme and the CD11b (C3bi-R), CD11c (p150, 95) CD14, CD68 (KPI) and Ber-Mac3 antigens. Double staining with the antibody Ki-67 demonstrated that the proliferating components were the CD30-positive cells and not the histiocytes. T-cell receptor beta gene rearrangements were shown in three cases tested. The patients responded well to aggressive chemotherapy and nine are still alive, eight in complete remission. It is suggested that the tumour represents a well-defined clinico-pathological entity originating from activated T-lymphocytes.

Adolescent↗