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Biomedical subjects

I Sanjuán

Publications and source records attributed to I Sanjuán.

At least 19 recordsLinked to original sources

Production of antigen-specific human monoclonal antibodies: comparison of mice carrying IgH/kappa or IgH/kappa/lambda transloci.

Here we compare human monoclonal antibody (MAb) production from mouse strains that carry disruptions of their endogenous mouse IgH/IgK loci and harbor human IgM + Igkappa(BABkappa) or human IgM + Igkappa + IgA transloci (BABkappa,lambda). We found that whereas both strains proved effective for the isolation of antigen-specific IgM antibodies, many of the IgM MAbs elicited from BABkappa comprise human mu chains that are associated with mouse lambda chains. In contrast, BABkappa,lambda mice gave rise to fully functional, polymeric human IgM antibodies comprising both human IgH and human IgL chains. Therefore, the inclusion of a human Iglambda translocus (in addition to the human IgH + Igkappa transloci) not only diminishes problems of endogenous mouse Iglambda expression but also provides a strain of mice that yields fully human MAbs to a wide range of antigens, as witnessed by the isolation of MAbs to human blood cells, tumor cell lines, and an immunoglobulin idiotype.

Animals↗

Cord blood transplants: early recovery of neutrophils from co-transplanted sibling haploidentical progenitor cells and lack of engraftment of cultured cord blood cells, as ascertained by analysis of DNA polymorphisms.

The number of infused cells is a very important factor in cord blood transplant (CBT) engraftment. Prior ex vivo expansion of aliquots of transplanted cord blood (CB) units is being investigated as a procedure to increase engraftment potential, but results are difficult to evaluate due to a lack of markers for assessing the contribution of expanded cells. We transplanted five patients, infusing the best available CB unit and cells from a second donor simultaneously. In two patients, these cells were obtained from another frozen CB unit by CD34(+)positive selection and culture expansion; the other three patients received uncultured highly purified haploidentical CD34(+) cells. The first two patients had DNA from the culture expanded CB cells detected only for a few days around day +11 when the absolute neutrophil count (ANC) was >200/microl; thereafter and when the ANC was <500/microl, only donor DNA from the uncultured CB was detected. For the other three patients, DNA analysis showed early and transient granulocyte engraftment of haploidentical cells, progressively replaced by the CB-derived granulocytes. We concluded that: (1) simultaneous infusion of lymphocyte-depleted HLA highly mismatched haematopoietic progenitor cells has not produced unfavourable effects for CBT; (2) the double transplant model is suitable for evaluating the engraftment potential of ex vivocultured CB cells in the clinical setting; (3) the culture conditions used did not result in early recovery of ANC; and (4) co-transplantation of purified uncultured HLA haploidentical CD34(+) cells may reduce the time of neutropenia following CBT.

Acute Disease↗

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↗

[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↗

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↗

[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↗

[Interstitial pneumonia in bone marrow transplantation. Preventive and therapeutic aspects. Our experience and review of the literature].

From June/82 through November/85 bone marrow transplant recipients in our Institution were given only trimethoprim-sulfamethoxazole as prophylaxis against interstitial pneumonia. In December/85 we began a program of administration of passive immunoprophylaxis with hyperimmune plasma or cytomegalovirus-specific gamma globulin and transfusion of seronegative blood products to all bone marrow transplant recipients whether they were seropositive or seronegative prior to transplant. Nine of 36 patients in the historical control group and 9 of 32 patients in the study group developed an interstitial pneumonia. Interstitial pneumonia, once established, was treated empirically. The 9 patients in the control group received trimethoprim-sulfamethoxazole +/- adenine arabinoside, acyclovir, amphotericin B and anti-bacterial antibiotics; all died. Post-mortem study was performed in 7 (4 CMV, 3 idiopathic). The 9 patients in the study group received high dose cytomegalovirus-specific gamma globulin + acyclovir or ganciclovir in addition to the above measures. Four were cured, one relapsed and responded to treatment again. Five died (1 CMV, 1 candida, 3 idiopathic). We conclude that the prophylactic measures, as applied at our Institution, were inefficient. By contrast, therapy with specific immunoglobulin + acyclovir or ganciclovir can control a high percentage of patients. We compare this experience with reports from other centers.

Acyclovir↗