Biomedical subjects
Publications and source records attributed to M Rovira.
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BACKGROUND: Allogeneic bone marrow transplantation (BMT) is the only potentially curative treatment in multiple myeloma (MM). METHODS: From january 1986 to december 1993, 12 cases (10 males and 2 females) underwent BMT in the authors' institution. The mean age of the series was 39 years (range 23-49). The situation of the myeloma on initiation of the conditioning was: complete remission (CR) in 2 cases, objective response in 5 cases, partial response in 1 case and treatment resistance in 4 cases. The conditioning schedule included cyclophosphamide (120 mg/kg) and total body irradiation (10-14 Gy) with or without melfalan at high doses in 11 patients and busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) in 1 case. The prophylaxis of graft versus host disease (GVHD) was carried out with methotrexate and cyclosporine A (CsA) in 7 cases, CsA plus prednisone in 2 cases and 3 patients received CsA plus bone marrow partially depleted of T lymphocytes by elutriation. RESULTS: The situation of the myeloma with regard to response following transplantation was: unevaluable in 1 case, resistant in 1 case, objective response in 2 cases and CR in 8 cases. Seven out of the 10 patients at risk presented grades II-IV GVHD. Four of the 8 patients who were in CR following transplantation died due to post transplant complications and 2 out of the 6 relapsed 9 months after the transplant while 2 remain in CR at 5 and 8 years after the transplant, respectively. Nine patients died due to infection in 2 cases, GVHD and infection in 4 cases, GVHD and hemorrhage in 1 case and progression and infection in 2 cases. Of the 3 surviving patients, 1 relapsed at 14 months after the transplant and two remain in CR at 5 and 8 years post transplantation. CONCLUSIONS: Bone marrow transplantation conditioning gives place to a high number of complete remission in multiple myeloma. However, the incidence of acute grade II-IV graft versus host disease and mortality due to complications related to the transplantation are very high. Nonetheless, a proportion of patients may achieve curation with bone marrow transplantation.
BACKGROUND: Bone marrow transplantation (BMT) from a histocompatible donor is the only curative treatment in chronic myeloid leukemia (CML). Only a minority of patients dispose of an adequate donor from among his/her relatives. The remaining transplant receptors must look to unrelated donors (URD). The experience of the Escuela de Hematología Farreras Valentí (Farreras Valentí School of Hematology, Barcelona, Spain) in BMT from URD in CML in the first chronic phase is herein reported. METHODS: Fifteen patients (9 males and 6 females, median age 33 years; range 14-48 years) were transplanted from October 1988 to May 1994. Serologic identity was expressed in the A, B and D loci in 9 cases and minor incompatibility in 6. Conditioning included total body irradiation and cyclophosphamide in 14 patients and busulphan plus cyclophosphamide in 1. Partial and selective T lymphocyte depletion was performed by elutriation in 7 cases. RESULTS: Primary implant failure was detected in 2 out of 14 risk patients (14%) and secondary failure was observed in 3 out of 12 cases (25%). The actuarial probability of acute graft versus host disease (GVHD) was 55 +/- 15% at 7 weeks with a probability of appearance with an intensity of II-IV of 31 +/- 13%. Five out of 7 patients with a survival of greater than 100 days, developed chronic GVHD (71%). Ten presented fatal complications. In 5 cases, death was due to pulmonary problems. Recurrence of CML was not observed in any of the patients in the series. The probability of disease free survival at 2 years was 30 +/- 12%. CONCLUSIONS: Bone marrow transplantation from an unrelated donor is an effective treatment for a proportion of patients with chronic myeloid leukemia although severe complications are frequent and originate a high mortality.
In the past 4 years we have treated four patients with a total of 19 fetal liver infusions (FLI). Two cases of refractory anemia with excess blasts in transformation (RAEB-t) were conditioned with cyclophosphamide and total body irradiation (1400 cGy) and were treated with FLI. In spite of such intensive conditioning, one patient recovered autologous hemopoiesis 3 weeks later, remaining in remission 4 years after this procedure. The second patient died with aplastic marrow on day 154, and the third suffered from severe aplastic anemia refractory to several types of conventional treatment. After FLI and without previous conditioning therapy a partial fetal engraftment was documented. This was transient and followed by autologous hemopoietic recovery and cure of the disease. The fourth patient had bone marrow failure in the setting of a severe pneumonia following autologous bone marrow transplantation. Ten days after FLI the hematological parameters dramatically improved and the pneumonia resolved. Autologous reconstitution of hemopoiesis was demonstrated. These experiences suggest that FLI might stimulate autologous hemopoiesis. This therapeutic approach may be useful to treat bone marrow failure when there is no response to first-line therapy. In hematologic malignancies with an indication for stem cell transplantation, other sources such as allogeneic or autologous bone marrow seem preferable to fetal liver cells.
Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a haematological disorder characterized by severe thrombocytopenia due to an immunologically induced absence of megakaryocytes in an otherwise normal-appearing bone marrow. A 57-year-old male with a 6-month history of rectal and cutaneous bleeding is reported. Platelet count was 10 X 10(9)/l, while other haematological values were within the normal range, except for the presence of hypogammaglobulinaemia with decreased IgA and IgG. Both platelet median volume and half-life span were normal, and antiplatelet IgG determinations were negative. Bone marrow aspiration and biopsy showed no megakaryocytes, with a normal appearance of erythroblastic and granulopoietic series. An in vitro culture for megakaryocytic progenitor cells did not show any growth of megakaryocyte colonies. No inhibitory effect on the growth of normal marrow megakaryocytic colonies was observed when serum and lymphocytes of the patient were added. Following 4 weeks of prednisone therapy, the platelet count rose to 127 X 10(9)/l and the bone marrow aspirate showed some megakaryocytes. The possible pathogenetic mechanisms of this entity are discussed.
In a series of 218 subjects diagnosed as having nonleukemic chronic myeloproliferative disorders in a single institution within a 18-year period, 13 instances of acute transformation were registered. They corresponded to 8 out of 70 patients with idiopathic myelofibrosis (IM), 4 out of 91 with polycythemia vera (PV), and 1 out of 57 with essential thrombocythemia (ET). The actuarial probability of developing such a complication at 100 months from diagnosis reached 20.6% in IM, 8.7% in PV, and 4% in ET. Only 1 IM patient whose condition developed into acute leukemia had received prior cytolytic therapy, whereas, in contrast, all PV and ET patients showing this pattern had previously been treated with either 32P or alkylating agents. On the other hand, acute transformation in IM generally had an insidious presentation, contrasting with its abrupt onset in most PV and ET patients. Most acute leukemias (12 out of 13) exhibited a myeloid phenotype. The patients' median survival from diagnosis of the acute transformation was only 3 months, the development of this complication significantly shortening the patients' overall survival.
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A 60-year-old man receiving chemotherapy for an intermediate-grade non-Hodgkin's lymphoma developed multiple papuloerythematous cutaneous lesions. Alternaria alternata was cultured from the lesions, and hyphae were seen in biopsy specimens. This is an unusual infection, without a well-established treatment, in patients with lymphoma. The use of amphotericin B resulted in cure.
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The treatment of patients with refractory bone marrow aplasia in whom bone marrow transplant cannot be performed is unsatisfactory. Infections and haemorrhages are the most frequent cause of death in such patients. Human recombinant proteins from haemopoietic growth factors provide new therapeutic possibilities. The clinical and biologic course of one such patient treated with rhGM-CSF is reported here. The patient had severe bone marrow aplasia refractory to immunosuppressive treatment, and an improvement of leucocyte, neutrophil and eosinophil counts, along with the healing of an infection only partially controlled with antibiotics, followed the administration of rhGM-CSF. However, such peripheral blood improvement was not accompanied by any increase of bone marrow cellularity, as measured by conventional histopathologic methods, and the patient died due to ictero-ascitic evolution of post-transfusion chronic liver disease.
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.
We have gone through the computerized tomographies (CT) of four cases of spinal epidural lymphomas (SEL) studied in our department. Paraparesis with a sensitive level was the beginning of the disease three times; sciatic pain with recurrent fever once. A myelography followed by CT was done in the three cases of paraparesis while a non-contrast CT and a contrast-enhanced study was done in the case of sciatic pain. An homogeneous intraspinal mass stretching at least along one vertebral segment was the most usual finding. This mass spread into paraspinal tissue effacing fat lines. The mass was hyperdense in relation to dural sack and was limited to intraspinal space in one occasion. We have revised bibliography about osseous lesions in SEL and have found out disagreement on it. We have found them only once in our study. Intrathecal contrast was useless in determining tumour nature but useful in delimiting intraspinal extent. We have searched for tomographic features in order to establish differential diagnosis with other spinal epidural diseases. We did not find any SEL-exclusive features but we found that an homogeneous intra-extraspinal mass, extended at least along one vertebral segment and either producing or not producing osseous lesions can make us think of the presence of spinal epidural lymphoma.
The results achieved in a series of 63 patients diagnosed of multiple myeloma in one Centre between February 1981 and December 1984 are reported. One patient was in stage IA, 27 in stage II (A, 24; B, 3), and the remaining 35 were in stage III (A, 22; B, 13). The initial therapy consisted of courses of vincristine, cyclophosphamide, melphalan and prednisone combination chemotherapy (VCMP) given every 4th week. Among the 56 patients who were evaluable, 28 (50%) showed objective response, 6 (10.7%) clinical improvement, and therapeutical failure was seen in 14, whereas 8 patients died during the first two months of treatment. The haematological tolerance to VCMP was acceptable, but neurotoxicity due to vincristine appeared in 17.8% of the cases. Thirty-two patients showing resistance to VCMP at any given moment received vincristine, BCNU, adriamycin and prednisone or dexamethasone (VBAP/D) as salvage therapy, only 5 responses (15.6%) being achieved. Only 5 patients are still alive and the median survival of the series is 23 months. Progression of the disease and infections were the major causes of death.
The frequency and features of associated neoplastic diseases and their impact on survival were evaluated in a series of 232 patients with chronic lymphocytic leukemia (CLL) who had been diagnosed during an 18 year period. Thirty-two patients (13.8%) had overall 38 neoplasias, 27 of which were diagnosed after CLL. There were no significant differences in the initial clinical and hematological features of the patients depending on whether they had or not a second neoplastic disease or on the time of its development. When compared with the normal population of similar age and sex, the patients with CLL, particularly females, had and increased risk to develop other tumors. The actuarial analysis showed that the risk of developing associated tumors increased through time up to 36% nine years after the diagnosis (27% when skin neoplasias were excluded). Although differences in survival were not found between patients with CLL and associated tumor and the rest of the series, most patients with noncutaneous neoplasia died as a direct consequence of it 18 months after its diagnosis.
Myelodysplastic syndromes (MDS) are disorders characterized by a profound impairment of proliferation and maturation of hematopoietic cells. The prognosis is poor owing to the occurrence of severe cytopenia or to the common leukemic transformation of these conditions. At present there is no available effective treatment for patients with MDS. A patient is reported with simple refractory anemia which responded to therapy with high doses of maturative factors (folic acid and vitamin B12). This therapy resulted in the disappearance of transfusion requirements and in the increase of peripheral blood cell counts. It is concluded that, in view of the lack of toxicity of the treatment with madurative factors, this therapy should be attempted in a sequential fashion in all patients with MSD.
A 43-year-old woman had abdominal pain and anemia due to inorganic lead poisoning. Plain abdominal x-ray films showed metallic densities within the lumen of the large bowel. The patient admitted that she used to chew the sheets of metallic lead enclosing wine bottle necks regularly. We report the case because of both the unusual radiographic findings and the exceptional source of lead intoxication.
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The role played by alpha interferon (alpha-IFN) in the treatment of B-type chronic lymphocytic leukaemia (B-CLL) has been studied by different authors. Despite the inconclusiveness of the results, alpha-IFN seems to be more effective in those patients with low tumour burden (early stages) who have been previously untreated. Although the mechanism of action of alpha-IFN is not wholly understood, it is known that this agent is a strong stimulant of the natural killer lymphocytes (NK). NK activity has been found decreased in B-CLL. In the present work the effect of alpha-IFN on NK activity was studied in 9 previously untreated B-CLL patients in stage A, who received chlorambucil (CLB) followed by alpha-IFN for at least 4 months. The disease stage did not change in most of the patients during alkylating or IFN therapy. CLB failed to increase NK activity, although it diminished the lymphocyte count. Although the lymphocyte count of the patients treated with alpha-IFN was not reduced beyond the values attained by CLB, NK activity reached normal values in 5 of the 7 patients in whom this was low, and kept within normal ranges in the two patients with normal NK activity. The number of CD57+ lymphocytes (this being the antigen present in NK cells) increased after alpha-IFN treatment, without any changes in the remaining T-lymphocyte (CD2, CD4 and CD8) and NK (CD16 and CD11b) subpopulations. These results show that alpha-IFN enhances NK activity in vivo.