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.

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.

Autoimmune mediated thrombocytopenia associated with the use of interferon-alpha in chronic myeloid leukemia.

We report on two patients with Ph+ chronic myeloid leukemia (CML) in chronic phase who developed severe thrombocytopenia during treatment with interferon-alpha 2A (IFN-alpha 2A). In both cases, we detected the presence of platelet-associated antibodies (PAIg) by autoimmune flow cytometry. We postulated an immune mediated platelet destruction mechanism; corticosteroid therapy was employed and interferon therapy was withdrawn, resulting in an increase in platelet count and a reduction of PAIg.

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).

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.

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.

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.

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.

Neutralizing anti-interferon-alpha antibodies and response to treatment in patients with Ph+ chronic myeloid leukaemia sequentially treated with recombinant (alpha 2a) and lymphoblastoid interferon-alpha.

Neutralizing anti-IFN alpha antibodies (nIFN alpha Abs) occur in a significant proportion of patients with hairy cell leukaemia, hepatitis or solid tumours treated with recombinant IFN alpha (IFN alpha 2a or IFN alpha 2b), but information on their incidence in chronic myeloid leukaemia (CML) is scanty and their clinical relevance is not yet completely defined. By using an IFN alpha antiviral neutralization bioassay, the frequency of nIFN alpha 2a Abs was evaluated in 67Ph+ CML patients during IFN alpha 2a therapy at doses ranging from 6 to 9 MU/d. 15 patients (22%) developed nIFN alpha 2a Abs (titre ranging from 1:40 to 1:20480) and 11/15 (73%) were haematologically and/or karyotypically unresponsive to treatment.

Immunologic and clinical modifications following low-dose subcutaneous administration of rIL-2 in non-Hodgkin's lymphoma patients after autologous bone marrow transplantation.

In order to induce a therapeutic immunomodulatory activity, 11 patients with high-grade non-Hodgkin's lymphoma (HG-NHL) at a median of 42 days after autologous bone marrow transplantation (ABMT) received recombinant interleukin-2 (rIL-2) subcutaneously at a dose of 2 international megaunits (IMU)/m2 every other day for 2 weeks and then 3 IMU/m2 twice a week for 1 year. Immunological studies, including T and natural killer (NK) cell subset assessment, together with functional assay, such as NK and CD16-mediated cytotoxic activities, were performed before therapy, after 2 weeks and then monthly. Phenotypic analyses showed a significant and persistant (P = 0.

Interferon-alpha and hydroxyurea in early chronic myeloid leukemia: a comparative analysis of the Italian and German chronic myeloid leukemia trials with interferon-alpha.

In 1994, the Italian and the German Chronic myeloid leukemia (CML) trials comparing interferon-alpha (IFN-alpha) with conventional chemotherapy were published. The survival advantage in favor of IFN-alpha compared with hydroxyurea (HU; 72 v 52 months) was significant in the Italian (P < .002), but not in the German trial (66 v 56 months, P < .

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.

Monitoring bulky mediastinal disease with gallium-67, CT-scan and magnetic resonance imaging in Hodgkin's disease and high-grade non-Hodgkin's lymphoma.

Treatment of both Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (HG-NHL) with bulky presentation at diagnosis frequently results in residual masses detected radiologically. Conventional diagnostic radiology and computed tomography (CT) are generally unable to detect the differences between tumor tissue and fibrosis. Gallium-67-citrate (67Ga) SPECT and magnetic resonance imaging (MRI) can potentially differentiate residual active tumor tissue and fibrosis.

A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

We retrospectively compared the outcome in patients in the EBMT database transplanted for acute leukaemia from January 1987 to January 1994 who received busulphan and cyclophosphamide (BU/CY) as a pretransplant regimen versus those who received cyclophosphamide and total-body irradiation (CY/TBI). The patients were matched for type of transplant (autologous bone marrow transplantation (ABMT) versus allogeneic (BMT)), diagnosis (acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML)), status (early (first complete remission, CR-1) versus intermediate (second or later remission, first relapse)), age, FAB classification for AML, prevention of graft-versus-host disease and year of transplantation. In ABMT recipients (matched paired 530 x 2) with ALL CR-1, AML CR-1 and AML intermediate disease, transplant-related mortalities (TRM) relapse incidence (RI) and leukaemia-free survival (LFS) did not differ significantly in patients treated with BU/CY or CY/TBI.

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%).

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.

A new method of "in-cell reverse transcriptase-polymerase chain reaction" for the detection of BCR/ABL transcript in chronic myeloid leukemia patients.

Methods of detecting minimal residual disease (MRD) in chronic myeloid leukemia (CML) include chromosome analysis, Southern blotting, polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) techniques. We report a novel method to detect intracellular messenger RNA (mRNA) by combining the techniques of reverse transcription (RT) and PCR performed directly inside the cells, without extraction of the nucleic acid. We applied this method, which we call "in-cell RT-PCR", to detect hybrid BCR/ABL transcript within single cells.

'Fingerprinting' of HLA-DQA by polymerase chain reaction and heteroduplex analysis.

We have developed a rapid, non-radioisotopic PCR fingerprinting technique for analysis of the HLA-Class II DQA gene second exon polymorphism, and have applied it to DNA samples from 210 healthy individuals. The technique is based on the formation of specific patterns (fingerprints) of homoduplexes or heteroduplexes between in vitro amplified DNA sequences. After electrophoresis on non-denaturing polyacrylamide gels and ethidium bromide fluorescence or silver staining, different HLA-DQA types give allele-specific banding patterns.

Primary Mediastinal B-cell lymphoma with sclerosis: clinical and therapeutic evaluation of 22 patients.

In the last decade, there have been several reports on what is now recognized as a new clinical and pathological entity termed primarily mediastinal B-cell lymphoma (PMBCL) with sclerosis. This lymphoma presents unique clinical characteristics with an aggressive outcome and, at present, the best approach seems to be a combination of chemotherapy and radiotherapy. Between June 1989 and September 1994, twenty-two previously untreated patients with PMBCL with sclerosis were treated with a combination of third-generation chemotherapy regimen (MACOP-B or F-MACHOP) and mediastinal irradiation.

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.

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.

FLU-ID (fludarabine and idarubicin) regimen as salvage therapy in pretreated low-grade non-Hodgkin's lymphoma.

Fludarabine (FLU) is a new antimetabolite chemotherapeutic agent with promising activity in lymphoproliferative disorders and, in particular, in low-grade non-Hodgkin's lymphoma (LG-NHL). Recently, a few reports have described interesting results using FLU in polychemotherapy regimens. In order to evaluate FLU in combination with other antineoplastic agents, we used a combination of FLU and idarubicin, called the FLU-ID regimen, to treat 10 patients with recurrent LG-NHL.

All-trans-retinoic acid and pseudotumor cerebri in a young adult with acute promyelocytic leukemia: a possible disease association.

Pseudotumor cerebri or idiopathic intracranial hypertension is a neurological syndrome characterized by signs and symptoms of intracranial hypertension without clinical or 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 report on a case observed in an older patient (young adult age) and give diagnostic and therapeutic guidelines.

Supradiaphragmatic early stage Hodgkin's disease: does mantle radiation therapy still have a role?

Extended field radiation therapy represents the main therapeutic option in early stage Hodgkin's disease with favorable prognostic features. Its role however has recently been criticized, mainly due to the high incidence of late complications in irradiated tissues. Furthermore, surgical staging, which in the opinion of many is mandatory for proper selection of patients for radiotherapy alone, has a well-known morbidity, and splenectomy has been associated with a high risk of secondary leukemias.