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Biomedical subjects

R Forés

Publications and source records attributed to R Forés.

At least 19 recordsLinked to original sources

Infusion of lymphocytes obtained from a donor immunised with the paraprotein idiotype as a treatment in a relapsed myeloma.

A 48-year-old patient with IgA k multiple myeloma received a BMT from his HLA-matched sibling. After transplantation, the disease relapsed. Melphalan therapy followed by reinfusion of haemopoietic blood stem cells collected from the patient led to the improvement of the clinical status, although mixed chimerism and an elevated serum IgA persisted. Successful donor immunisation against an immunogenic preparation of the recipient monoclonal protein was performed before the infusion of donor T lymphocytes (DLI) into the patient. Ten weeks after the lymphocyte infusions, no monoclonal band was evidenced and donor complete chimerism was detected. The patient did not develop GVHD. Once complete remission was achieved, the idiotype vaccine was administered to the patient. Nineteen months after DLI, the patient remains in remission. Bone Marrow Transplantation (2000).

Antineoplastic Agents, Alkylating↗

Umbilical cord blood banking for unrelated transplantation: evaluation of cell separation and storage methods.

Cost-efficient umbilical cord blood (UCB) banking requires well-standardized methods of volume reduction and storage. To compare UCB fractionation using a technique of hydroxyethyl starch (HES) sedimentation with the Ficoll (double) and Percoll methods, 50 whole units was allocated randomly to each procedure. HES resulted in a significantly better recovery of mononuclear cells (87.5%), granulocyte/macrophage colony-forming units (CFU-GM) (88.4%), and CD34- cells (87.4%) and lesser volume reduction (85.5%). HES was the least laborious, time consuming, and expensive of the three procedures, costing 3.4- and 4.4-fold less than the Ficoll and Percoll methods, respectively. Five units processed by each method was frozen in 4.5-mL cryotubes under optimal conditions. After thawing, the greatest degree of recovery of viable nucleated cells and number of CFU-GM per unit were obtained using the HES procedure. Using 4.5-mL cryotubes, the calculated number of units that could be stored in 600-L containers was 3.8- and 2.2-fold higher for Ficoll- and Percoll-separated than for HES-separated units, respectively. Nevertheless, the higher direct costs of the density gradient separation procedures outweighed their lower storage cost. For long-term cryopreservation, we assessed the freezing of HES-processed units in 50-mL cryobags and their specifically designed canisters. We found cell recoveries similar to those obtained with cryotubes, but storage capacity was decreased. Special racks designed for these canisters resulted in a 5-fold increase over the number of units stored in standard cryobags. This system also is feasible for Percoll- and Ficoll-separated units, resulting in comparable storage costs for the three separation methods. We conclude that this HES procedure and the 50-mL cryobags constitute a cost-efficient system for large-scale UCB banking.

Blood Preservation↗

[Detection of PNH clones using flow cytometry in aplastic anemia and paroxysmal nocturnal hemoglobinuria].

PURPOSE: To detect and quantify by flow cytometry (FC) PNH clones in paroxysmal nocturnal haemoglobinuria (PNH) and aplastic anaemia (AA) patients. PATIENTS AND METHODS: We have performed a flow cytometric analysis to determine the granulocyte expression of CD55 and CD59 from 29 patients with AA and 11 patients with PNH. RESULTS: In the 11 PNH patients the study showed 58 +/- 34% and 56 +/- 32% (mean +/- SD) CD55(-) y CD59(-) granulocytes. A good correlation was found between the results of FC and haemolysis. The follow-up study showed PNH clone progression in one case and stability in 5 cases. Among 11 AA patients studied at diagnosis, two presented a population of CD55(-) granulocytes (14% and 48%) with CD59 normal, this defect disappeared in both patients after immunosuppressive therapy. The FC study revealed PNH clones in 7 cases among the 26 analyzed after treatment (23 with ATG and/or CyA), in 3 cases with negative Ham's test (in two this became positive 6 and 12 months later). The mean values obtained in these 7 patients with PNH-AA syndrome were 26 +/- 15% y 36 +/- 30% (mean +/- SD) CD55(-) and CD59(-) granulocytes. The median time from diagnosis to detection of PNH phenomenon was 83 months. In the follow-up study, 4 cases had stability, one case had a decrease and one a progression of the abnormal clone. In a retrospective analysis, among the 7 patients with PNH-AA syndrome, 5 had a partial response after the initial treatment. CONCLUSIONS: The FC on granulocytes is a useful method to diagnose and characterize PNH. This test is good for early detection of PNH clones in AA patients at initial diagnosis and in long term survivors. In both diseases it permits measuring the extent of the abnormal clone and its follow up. The extent of the defect is more related to haemolysis than the haematopoietic deficiency. PNH development seems to be more frequent in AA patients with incomplete response after immunosuppressive therapy and in some cases the defect could be latent at the time of diagnosis.

Adult↗

Detection of maternal DNA in umbilical cord blood by polymerase chain reaction amplification of minisatellite sequences.

One of the concerns about the use of cord blood as a source of hematopoietic stem cells for allogeneic transplantation is the possibility of contamination by maternal cells which could cause life-threatening GVHD. We have assessed cord blood contamination using PCR analysis of several minisatellite regions to detect maternal DNA. Eighty mother-cord pairs were obtained for this study. In one case there were no specific maternal alleles at any loci and, therefore, cord blood could not be evaluated. Thus, there was a total of 79 informative cases for the detection of maternal cells in the fetal circulation. In most cases, the level of detection was between 0.5 and 1%. We detected maternal DNA in the cord blood sample in only one case (1.26%), and the analysis of dilution experiments led to an estimate of 0.5-1% maternal cells. In conclusion, using PCR amplification of hypervariable regions, maternal DNA is very rarely detected in the cord blood collected at birth, although this approach has a relatively low level of sensitivity.

Chimera↗

Rhinocerebral mucormycosis following donor leukocyte infusion: successful treatment with liposomal amphotericin B and surgical debridement.

A 24-year-old male developed cytogenetic relapse of chronic myeloid leukemia (CML) four years after allogeneic BMT. After a year of treatment with IFN-alpha, he achieved a partial cytogenetic response. Treatment with donor leukocyte infusions (DLI) was given (total dose 1 x 10(8) T lymphocytes/kg). Two months later, he developed acute GVHD (skin and liver), that improved with CsA and methylprednisolone and resulted in cytogenetic remission with complete donor chimerism. One month later he developed rhinocerebral mucormycosis and was successfully treated with surgical debridement and liposomal amphotericin B (total dose 12 g). This is the first case of mucormycosis described after DLI.

Adult↗

Mucormycosis and hemopoietic transplants.

Mucormycosis is becoming recognized as a serious complication in patients undergoing hemopoietic transplantation (HT), because it is a major cause of morbidity and mortality. In our institution 4 cases of mucormycosis in post-HT period among 345 patients undergoing HT were diagnosed between 1984 and 1997. We studies the clinical characteristics of these cases and we conclude that mucormycosis is not a common infection in patients undergoing HT but that it is followed by a high morbidity and mortality. Maintained neutropenia is the most important risk factor.

Adult↗

Management of thrombotic microangiopathy following allogeneic transplantation: what is the role of plasma exchange?

Thrombotic microangiopathy (TMA) is an infrequent but serious complication of allogeneic transplantation. The success rate of plasma exchange (PE) reported in the treatment of this entity is a controversial subject. We report the outcome of 10 patients with TMA post-allogeneic transplantation after treatment with PE. Two out of the 10 patients have not responded, five had a partial response, but died of acute GVHD or interstitial pneumonitis, and three have responded and recovered. Our study suggests that there are different degrees of TMA severity. Only mild multifactorial cases with no severe hemolysis (LDH activity <1000 U/l) may be fully resolved with PE.

Adolescent↗

Epstein-Barr virus associated B-cell lymphoma after autologous bone marrow transplantation for T-cell acute lymphoblastic leukaemia.

Epstein-Barr virus associated lymphoproliferative disease after autologous bone marrow transplantation (ABMT) has rarely been reported. We report a case of B-cell lymphoma following ABMT for T-acute lymphoblastic leukaemia; bone marrow was purged in vitro with monoclonal antibodies to remove T cells. Immunoglobulin and T-cell receptor gene rearrangement studies were used to demonstrate clonality and to show that this patient developed a second neoplasm after ABMT. EBV proteins and genome (type A) were present in post-transplantation lymphoma, suggesting a causative role in its development.

Aged↗

Donor leukocyte infusions for treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation.

A 24-year-old man with acute myelomonocytic leukemia (AML-M4) who relapsed 6 months after an allogeneic BMT was treated with chemotherapy followed by donor leukocyte infusions (4.19 x 10(8) mononuclear cells/kg). The patient developed grade II acute GVHD that responded to therapy with CsA and prednisone. Chimerism was assessed by PCR amplification of the MCT 118 hypervariable region. Fourteen months after donor leukocyte infusions the patient remains in complete remission, without any morphologic and cytogenetic evidence of leukemia, and with a complete donor chimerism. This case shows that donor leukocyte infusions are an effective therapy for some acute myeloid leukemia patients who relapse after allogeneic BMT.

Adult↗

HLA haploidentical cord blood cell transplant in a 15-year-old, 50 kg weight patient: successful treatment for chronic myeloid leukemia after myeloid blastic transformation.

A 15-year-old, 50 kg weight patient with CML had a myeloblastic transformation which reverted to Ph negative remission with intensive chemotherapy 5 years after diagnosis. Umbilical cord blood (UCB) from an HLA-haploidentical sister had been frozen 2 years and 9 months before, as she had no HLA-identical sibling and no suitable unrelated donor had been found. UCB transplant was selected on the basis of previous general experience with this kind of transplant, lack of a better choice of donor, and likelihood of a prompt relapse of the disease without delay and the patient developed grade II aGVHD as well as severe CsA toxicity which required discontinuation of the drug, anti-IL2r being given instead. Subsequently she only had histologic evidence of cGVHD and 1.5 years after the transplant she remains in complete hematologic remission with full chimerism and without evidence of the bcr/abl fusion gene. This case illustrates further possibilities of allo-transplantation using UCB.

Adolescent↗

Diagnosis of transfusion-associated graft-versus-host disease by polymerase chain reaction in fludarabine-treated B-chronic lymphocytic leukaemia.

Transfusion-associated graft-versus-host disease (TA-GVHD), has rarely been reported associated with B-chronic lymphocytic leukaemia (B-CLL). We report a patient diagnosed with B-CLL, previously treated with fludarabine, who developed TA-GVHD after being transfused during surgery for splenectomy. Diagnosis was confirmed by polymerase chain reaction (PCR) detection of donor DNA in the patient, by amplification of Y-chromosome sequence and analysis of minisatellite polymorphisms. B-CLL patients treated with fludarabine appear to be at risk for TA-GVHD and should be regarded as candidates for transfusions with irradiated blood products. This case illustrates that PCR is a rapid technique for the early diagnosis of TA-GVHD.

Antineoplastic Agents↗

Flow cytometric analysis of decay-accelerating factor (CD55) on neutrophils from aplastic anaemia patients.

Using a flow cytometric analysis, CD55 (decay-accelerating factor), CD59 and CD58 have been measured on neutrophils from 12 aplastic anaemia (AA) patients who were long-term survivors after immunosuppressive therapy (IS), 17 healthy individuals, four patients with PNH, and six patients with other haematological disorders. The neutrophils from normal control patients and the six patients with other haematological disorders showed 98 +/- 2% (mean +/- SD) positive granulocytes for CD55. Corresponding values were low (12%, 26%, 51% and 58%) on the primarily PNH patients. Among the 12 AA patients examined, seven had normal and five low values (59% in two, 70%, 71% and 82%). Among the five AA patients who showed CD55 neutrophil deficiency, four had showed an incomplete response after the initial IS treatment and the other relapsed following an initial haematological complete response; three cases had a positive Ham's test and two were negative. Our data suggest that the development of PNH clones is a frequent finding in AA long-term survivors, mainly in those who had shown an incomplete response following IS. Neutrophil CD55 expression analysis by flow cytometry could be useful to detect clonal evolution in these patients.

Adult↗

[Efficacy of various treatments in the management of idiopathic thrombocytopenic purpura in the adult].

PURPOSE: To evaluate the ITP treatment modalities and their results in a series of 30 adult patients. PATIENTS AND METHODS: 30 patients, age 15-74, were diagnosed of ITP in our institution between 1988 and December 1991. We defined the ITP as: mild (platelets > or = 50 x 10(9)/L and < or = 120 x 10(9)/L), moderate (platelets 25-50 x 10(9)/L) and severe (platelets < or = 25 x 10(9)/L). Treatment was initiated when the platelet count reached a level < 50 x 10(9)/L. Initial therapy was oral prednisone or methyl-prednisolone in all patients. In 12 unresponsive patients the treatment included splenectomy. Patients who fail steroid therapy and splenectomy received additional lines of therapy, that included: vincristine (n = 2), vinblastine (n = 1), danazol (n = 5), anti D immunoglobulin (n = 6), methotrexate (n = 2), intravenous immunoglobulin (n = 3). RESULTS: Complete remission was obtained in 19 patients with a follow-up of 3 to 55 months (median, 30 months). Partial remission was achieved in 4 patients, that was sustained for 9 to 39 months (median, 22.5 months) after initial therapy. One unresponsive patient died of infection. Six mild ITP patients did not require therapy with a follow-up of 14 to 56 months (median, 33.1 months). CONCLUSION: In adult patients with mild ITP, therapy is not required. Steroid therapy remains the initial therapeutic choice for moderate and severe ITP. In unresponsive patients useful alternative choices are splenectomy, danazol, anti D immunoglobulin and methotrexate.

Adolescent↗

[Treatment with fludarabine of chronic refractory lymphoid leukemia].

PURPOSE: New antimetabolic drugs, purine-analogous, have been introduced in the treatment of advanced or refractory cases of chronic lymphocytic leukaemia (CLL), fludarabine (FLU) being one of such drugs. The results attained with FLU in 6 cases of refractory CLL are reported. PATIENTS AND METHODS: The efficacy and toxicity of FLU was evaluated in 6 patients (median age 63 years) between March 1993 and March 1994. Five patients were in stage III-IV and one in stage II of the Rai's system, and they were refractory to the usual treatment. The dosis used here was 30 mg/sq m/day, for 5 days every 4 weeks, up to a total of 6 therapeutic courses. The response was assessed after 3 and 6 courses. Anti-infectious prophylaxis was made with co-trimoxazole, monthly benzathine penicillin G and isoniazid in Mantoux-positive patients. The response criteria were those given by the NIC Working Group for CLL. RESULTS: The patients received 2 to 6 courses. None of them attained complete remission: 1 had nodular remission, 2 had partial remission, 2 responded partially although not reaching criteria for partial remission (1 died of pancytopenia), and 1 had disease progression and died after the second course. Fast and important reduction of the lymphocyte count as well as the CD4 lymphocytes was present in all cases. Bone-marrow infiltration decreased strikingly in 2 cases and the platelet count improved in 3 cases and worsened in 2 others. The following toxicity was recorded: 2 patients had nausea, 5 had neutropenia (below 500 x 10(9)/L in 3 instances) and 4 had thrombocytopenia (lower than 40 x 10(9)/L in one case). In 26 therapeutic courses there were 10 febrile episodes (1 for pneumonia, 1 for gastroenteritis and 8 without any septic foci); 1 patient developed pulmonary tuberculosis after completing the treatment and one patient died of posttransfusion graft versus host disease after splenectomy once she had completes six courses. CONCLUSION: This experience confirms the efficacy of FLU in the treatment of refractory B-CLL patients and is in agreement with previous reports as no response is initiated after the 3rd course. The lymphocyte count decreases quickly and strikingly. Depletion of CD4 lymphocytes along with neutropenia and hypogammaglobulinaemia make these patients highly sensitive to all types of infection, chiefly by opportunistic germs, so adequate anti-infectious prophylaxis is of great importance. The two patients with pre-treatment haemoglobin and platelet values lower than 10 g/dL and 40 x 10(9)/L, respectively, were the only ones in need of transfusion. No cumulative myelosuppression was appreciated.

Aged↗