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A 47 year old woman with a MALT lymphoma affecting the breast exclusively is reported. Complete response was achieved after CHOP chemotherapy but three years later a relapse was observed. Second-line chemotherapy (CNOP) and local radiotherapy were administered, and a second remission was obtained lasting for 1 year at last follow-up. A bibliographic search of MALT lymphomas of the breast showed that most such cases correspond to localized forms (stage I-II) and that from the radiologic point of view nodular lesions are almost the rule, although in the present case diffuse involvement was observed. MALT lymphomas of the breast tend to remain localized, and to relapse locally, and these facts appear as independent of the treatment applied (surgery, radiotherapy, chemotherapy or any combination).

The increase in cancer incidence in renal transplant recipients is a well recognized fact, which has been related to post-transplant immunosuppressive therapy. Solid tumors, skin cancer and non-Hodgkin's lymphomas account for most of the neoplasms in these patients, whereas chronic myeloproliferative disorders are infrequent. A patient is reported who developed chronic myelogenous leukemia (CML) six years after renal transplantation, which was followed by immunosuppressive with azathioprine, and the published data on such an association are reviewed. In all 10 cases reported azathioprine had been administered after transplantation. The amount and type of post-transplant immunosuppressive therapy seems to be the most important risk factor for the development of secondary CML in these patients, since no cases of CML in patients receiving cyclosporine A have been reported.

Abnormal chromatin clumping syndrome (ACCS) is a rare granulocyte disease halfway between Ph'-negative chronic myelogenous leukaemia (CML) and the myelodysplastic syndromes. A new case of such syndrome is presented, the patient being a 65 year-old man with anaemia, thrombocytopenia and myelaemic leucocytosis with abnormal condensation of the neutrophils' chromatin. Marked granulocytic hyperplasia was present in the bone marrow with strikingly dysplastic features, along with a decrease of the remaining blood cell lines. Irregular nuclear outlines and heterochromatin clumps separated by euchromatin bands were seen in the more mature granulocytes upon ultrastructural studies. No cytogenetic abnormalities were found in the bone marrow, and no ber-abl gene rearrangement was present in white cells from peripheral blood. The clinical course was marked by persistence of the anaemia and increasing leucocytosis which required 6-mercaptopurine treatment. Acute myeloblastic leukaemia occurred one year later and the patient died shortly after. It was concluded, from this case and others reported in the literature, that, with regard to its clinical course and proliferative character, ACCS is closer to Ph'-negative, bcr-abl negative CML rather than to the myelodysplastic syndromes.

Purpose: To analyse the clinical, biological and evolutive characteristics of 10 patients with multiple myeloma (MM) previously diagnosed of monoclonal gammopathy of uncertain significance (MGUS)., Patients and Methods: Ten patients with diagnostic criteria of MM, included in a series of 114 subjects with MGUS, IgG (92 cases), IgA (21 cases) or biclonal IgG+IgA (1 case), diagnosed between 1970 and 1990, comprise this study group., Results: The actuarial risk of developing MM in the series of 114 MGUS was 7.25% (95% CI: 1.5-13) and 16.1% (05% CI: 4.7-27.5) at 5 and 10 years of follow-up, respectively. MM occurred suddenly, both on clinical and biological grounds, in 8 of the 10 patients. The median period between the diagnosis of MGUS and the onset of MM was 48 months (range, 12-153). IgG MM appeared in 5 instances and IgA MM in 5 others. Bone pain (7 cases) and hypercalcaemic encephalopathy (2 cases) were the commonest clinical manifestations. Osteolytic lesions were found in the x-ray scan in 9 patients. Eight patients received chemotherapy, objective response being seen in five of them. The median survival since the diagnosis of MM was 18 months (range, 0.1-95). The causes of death in 8 deceased patients include disease progression (4 cases), pneumonia (3 cases) and neoplasm of the bladder (1 case)., Conclusions: This analysis shows the difficulties in predicting the outcome of MGUS, since most of the MM seen here occurred abruptly and after a highly variable length of time. Thus, patients with MGUS must be followed-up for undetermined time.

Purpose: To analyse the status of iron deposits at diagnosis in patients with idiopathic myelofibrosis (IM)., Patients and Methods: The study included twenty consecutive patients with IM. Haemoglobin, MCV, serum iron and serum ferritin were determined in each case. Perls stain was used to evaluate iron deposits in bone marrow samples attained by aspiration or biopsy. An attempt was made to correlate the semiquantitative estimation of bone marrow iron with the peripheral blood values connected with iron deposits., Results: Anaemia was present in 15 patients, but in most cases MCV and serum iron were normal. Iron deposits in bone marrow aspirate could be evaluated only in one patient as in the remainders no material was obtained. The semiquantitative estimation of iron in bone marrow biopsy samples showed diminished or absent deposits in 15 cases (75%). In contrast, none of the patients had decreased serum ferritin levels. No correlation was found between bone marrow iron and the peripheral blood values related to iron deposits., Conclusion: Most IM patients have decreased bone marrow iron deposits at diagnosis. However, as in chronic myelogenous leukaemia and in essential thrombocytopenia, such finding does not mean a true iron deficiency status.

Purpose: To analyse the frequency and the main clinico-haematologic characteristics of the patients with Ph'-positive chronic myelogenous leukaemia (CML) with long survival., Material and Methods: Of a series of 100 patients with CML diagnosed in the chronic phase and treated in the conventional way at the "Farreras Valentí" School of Haematology between 1969 and 1982, and followed-up for at least 10 years, those surviving more that 8-10 years since the diagnosis were considered eligible for this study. Their clinico-haematological characteristics at diagnosis were compared to those of the remaining patients by means of the Student's t and Mann-Whitney's U tests, plus chi square with the Yates correction. The actuarial survival in the series was assessed according to the Kaplan and Meier method. The Sokal prognostic index was calculated in the longest survivors., Results: The median survival of the series was 45 months (range: 4-171). Ninety-one patients died, 2 are alive in chronic phase and in 7 others the follow-up has been lost in the chronic phase. Eight patients survived more than 10 years and 14 more than eight years. Of these, six were men and eight women, 10 were under 50 years of age, one-half lacked splenomegaly at diagnosis and only 2 had Ph' chromosome mosaicism. According to the Sokal prognostic index, six of these patients were in the low-risk group, four were of intermediate risk, and four others were in the high-risk group. None of them had aplasia due to busulphan during the follow-up. When comparing the initial features of the patients surviving 8-10 years with those of the remainders, only the presence of a lower percentage of blast-cells (p = 0.03) and a lower number of blasts in peripheral blood (p = 0.01) in the former achieved statistically significant difference., Conclusions: These findings confirm the difficulty in identifying the CML patients with expected long survival at diagnosis. High numbers of cases must be analysed in order to attain definite conclusions in this regard.

Purpose: To evaluate in a sequential fashion the activity of the leukocyte alkaline phosphatase (LAP) in the chronic phase and the blastic crisis of chronic myelogenous leukaemia (CML)., Material and Methods: This study is comprised of 43 patients diagnosed of CML according to standard criteria. The initial LAP scores were compared with those recorded in the blastic crisis, using cytochemical methods. The statistical analysis was performed with Student's test and chi-square., Results: The LAP activity at diagnosis was low in 40 of the 43 cases (93%), the score being 0 in 20 instances. In the blastic crisis low scores were found in 27 patients (63%), while LAP activity appeared normal or increased in 16 others (37%). When the LAP scores of the two phases of the disease were compared the differences were found statistically significant (p less than 0.0001 and p less than 0.0007, respectively)., Conclusions: These results confirm that the onset of the blastic crisis of CML is often accompanied by an increase of the LAP activity, although this last persists low in the majority of the patients.

The clinico-haematological and evolutive features of five patients with Ph'-positive chronic myelogenous leukaemia (CML) whose initial profile suggested the diagnosis of essential thrombocythaemia (ET) were analysed. The patients were women with severe thrombocytosis (greater than or equal to 1000 x 10(9)/L) and moderate leucocytosis (less than 25 x 10(9)/L), and only two of them had splenomegaly. Increased basophil count in peripheral blood was present in all cases, and peripheral myelocytosis was seen in three. The molecular analysis showed rearrangement of the BCR gene in the three patients on which it was performed. Increasing leucocyte count was seen in the three patients with extended follow-up, this reaching values in accordance with CML. Finally, the three patients who died suffered a blastic crisis. The analysis of this series, along with others reported in the literature, suggests that such cases correspond to atypical forms of CML rather than actual TE patients.

The cause of death was revised in 109 cases of Ph'-positive chronic myelogenous leukaemia (CML) who died in a 15-year period. The median survival of the series, which included eight patients with initial criteria of blastic crisis, was 33.7 months (ranging between 2 and 192). Eight patients (7.3%) died during the chronic phase of the disease, 7 (6.4%) in the accelerated phase, and 94 (86.3%) in the blastic crisis. The cause of death in the chronic phase was frequently unrelated to CML (a second malignancy, cirrhosis of the liver, suicide, in four cases as opposed to infection, haemorrhage of hyperuricaemic renal failure in four others), but this was not so in the deaths occurred in the accelerated phase or blastic crisis. Thus, most of the deaths appearing in the accelerated phase were due to infection or haemorrhage, whereas in the blastic crisis they were mainly due to infection (54 of the 94 cases), followed by haemorrhage and leucostasis. All in all, these three complications were responsible for 94% of the deaths occurring in that evolutive phase of CML.

2'-Deoxycoformycin (DCF) is an experimental drug with specific lymphocytotoxic activity which has proved effective in the treatment of some lymphoproliferative syndromes (LPS). This paper deals with the results achieved in 6 patients with LPS, five of them with T-cell and one with B-cell malignancies, who received DCF as initial (2 cases) or salvage (4 cases) therapy. One patient with adult T-cell leukaemia-lymphoma achieved complete remission maintained for 36 months of follow-up; partial remission was attained in three others and the remaining two patients failed to respond to the treatment. Kidney toxicity was seen in three cases, and in two of them it was necessary to stop the treatment. Kidney toxicity was seen in three cases, and in two of them it was necessary to stop the treatment. Other untoward effects included nausea and vomiting (2 patients), myoclonus, dysaesthesia of the limbs and conjunctivitis arida (one case each). No haematologic or infectious complications were present in association with DCF treatment.

The anaemia accompanying chronic lymphocytic leukaemia (CLL) may have different causes (bone marrow infiltration, hypersplenism, immune haemolysis, haemorrhages) and is one of the poor-prognosis features of the disease. Treatment of advanced CLL patients with tumoral-infiltrative anaemia is based on chemotherapy. Nevertheless, some proofs seem to stress the important role played by suppressor T cells on the mechanism of the anaemia in such patients. As a result of these observations, cyclosporin A, a drug with proven efficacy in autoimmune diseases and bone marrow insufficiency, is being used in these cases. Three patients with advanced B-CLL and anaemia, refractory to treatment, received cyclosporin A (8-10 mg/kg, p.o. daily for 2-4 months). One of them recovered from anaemia and thrombocytopenia and is still in this situation after 11 months of suppression of therapy. Two other such cases are revised from the literature, as well as the role played by cyclosporin A in the therapy of CLL.

The evolutive patterns, actuarial survival and causes of death of idiopathic myelofibrosis were analysed in a series of 60 patients. The median age of the patients was 64 years; 41 were males and 19 females. In the initial bone-marrow biopsy studies 25 patients were in stage MF/C, 17 in MF/O- and 18 in MF/O+. When performing this analysis, 32 patients were dead, 19 were still alive and 9 had been lost after a median follow-up of 6 months. The median survival of the whole series was 57 months. Four major evolutive patterns were recorded: 1) blastic crisis (7 cases), 2) portal vein hypertension (4 cases), 3) liver insufficiency due to massive myeloid metaplasia of the liver without signs of portal vein hypertension (5 cases); in 2 of them this pattern followed splenectomy), and 4) heart failure ascribable, at least partially, to post-transfusion haemochromatosis (3 cases). The blastic crisis appearing in 7 patients presented after a median follow-up of 19 months, and 6 of these patients have died after a median of 5 months since the diagnosis of the blastic crisis. In the 16 patients who died without any characteristic evolutive pattern, the following causes of death could be registered: septic shock (6 cases), intracranial haemorrhage, haemoperitoneum and acute renal failure (1 case each), whereas the cause of the deceased was unclear in the remaining 7 patients.

The preliminary results of the LAL-86 protocol applied to 43 patients diagnosed of acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma (LL) between May 1986 and April 1989 are reported. Induction treatment consisted of one or two courses of vincristine, daunorubicin, prednisone, cytosine arabinoside and 6-thioguanine combination therapy. This phase was followed by consolidation treatment, in which VM-26, cyclophosphamide, BCNU and L-asparaginase were added to the former agents. Central nervous system prophylaxis was done with intrathecal methotrexate. Patients under 45 years of age with HLA identical sibs were subjected to allogeneic bone marrow transplantation (BMT) in the first complete remission (CR); when no HLA-identical sibs were available patients were randomised into autologous BMT or maintenance therapy. The remaining patients received maintenance chemotherapy. CR was achieved in 34 ALL patients (79%), 5 were refractory to treatment and 4 died during remission induction. Allogeneic BMT was carried out in 6 cases, autologous BMT in 3, and the remainders received chemotherapy. When performing this review, 7 patients had relapsed and the actuarial probability of 2-year duration of CR was 70%. Sixteen patients have died with a two-year disease-free survival probability of 60%. The preliminary results of the LAL-86 protocol are encouraging, but greater number of patients is needed, as well as a longer follow-up, to assess the effect of chemotherapy and compare these findings to the results of autologous or allogeneic BMT in the first RC.

A patient is presented in whom the diagnoses of chronic myelomonocytic leukaemia (CMML) and erythroblastopenia were simultaneously established. Besides the conventional criteria for both haemopathies, the culture of bone-marrow precursor cells showed lack of growth of the erythroid stem cells. 6-Mercaptopurine given as therapy for CMML failed to induce any favourable changes in erythroblastopenia, which in turn improved with prednisone. Nevertheless, the patients died five months after diagnosis due to acute transformation of the CMML.

Out of 113 cases of blastic crisis (BC) of Ph'-positive chronic myeloid leukaemia (CML), 13 had extramedullary involvement, this being the first BC manifestation in 5 instances. The median interval between extramedullary BC and bone marrow BC in these last was 2 months. Lymph nodes were the commonest extramedullary site of BC (8 cases), followed by osteoperiosteal and central nervous system (CNS). Lymph node BC occurred as generalised lymphadenopathy in most cases. Osteoperiosteal BC was seen as severe bone pain on osteolytic areas, whereas CNS blast crisis occurred as meningeal leukaemia in one case and chloroma in another. Lymphoid phenotype of blast cells was found in only 2 instances. The median survival of the patients after the onset of extramedullary involvement was 3 months.

Out of a series of 36 patients with chronic myelomonocytic leukaemia (CMML), five cases are reported with the association of this hemopathy to solid neoplasms. In two patients this last was a cutaneous tumour, while the remainders had, respectively, papilloma of the bladder, carcinoma of the sigma, and cutaneous T-cell lymphoma. These neoplasms were diagnosed in all cases prior to the discovery of CMML. When applying the "patient/year" method, significantly higher frequency of solid tumours was found for CMML patients, which would support the hypothesis that this myelodysplasia could be regarded as a paraneoplastic condition.