Miguel Ortín

The Bracton Centre, Oxleas NHS Trust, Дартфорде, England, United Kingdom

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Publications (14)58.25 Total impact

  • Miguel Ortín, Muhammad A Saif
    Immunotherapy 05/2012; 4(5):461-4. DOI:10.2217/imt.12.23 · 2.44 Impact Factor
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    ABSTRACT: There is a decrease in antibody levels after hematopoietic stem cell transplant (HSCT), and such patients may be at increased risk of acquiring vaccine-preventable infection. A simple and validated revaccination schedule is required. The aim of this study was to evaluate the immunogenicity of a revaccination schedule for pediatric HSCT recipients. Thirty-eight children (age, 1-18 years) who had undergone autologous or allogeneic HSCT for malignant diseases were recruited. All children received vaccinations in accordance with a predefined schedule. Antibody concentrations were measured before and 2-4 weeks after vaccination against tetanus; Haemophilus influenzae type b (Hib); meningococcus C; measles; poliovirus serotypes 1, 2, and 3; and 9 pneumococcus serotypes. Before vaccination, protective antibody levels were found for tetanus in 95% of patients (geometric mean concentration [GMC], 0.07 IU/mL; 95% CI, 0.05-0.1 IU/mL), for Hib in 63% (GMC, 0.34 microg/mL; 95% CI, 0.21-0.57 microg/mL), for measles in 60% (GMC, 102 mIU/mL; 95% CI, 41-253 mIU/mL), for meningococcus C in 11% (geometric mean titer [GMT], 1:4; 95% CI, 1:2-1:8.4), for all 3 poliovirus serotypes in 29%, and for all 9 pneumococcal serotypes in 0%. Vaccination resulted in a significant increase (P < or = .05) in antibody levels to each vaccine antigen studied, with 100% of patients achieving protection against tetanus (GMC, 2.2 IU/mL; 95% CI, 1.8-2.7 IU/mL), 100% achieving protection against Hib (GMC, 8.4 microg/mL; 95% CI, 7.6-9.3 microg/mL), 100% achieving protection against measles (GMC, 2435 mIU/mL; 95% CI, 1724-3439 mIU/mL), 100% achieving protection against meningococcus C (GMT, 1:5706; 95% CI, 1:3510-1:9272), 92% achieving protection against the 3 poliovirus serotypes, and > or = 80% achieving protection against each of the heptavalent pneumococcal conjugate vaccine-associated serotypes. No factors relevant to age, underlying disease, or treatment type were found to significantly influence responses. Revaccination of pediatric HSCT recipients in accordance with this revaccination schedule provides a high level of protection against these vaccine-preventable diseases.
    Clinical Infectious Diseases 04/2007; 44(5):625-34. DOI:10.1086/511641 · 9.42 Impact Factor
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    ABSTRACT: After the treatment of patients with acute leukemia, there is a decrease in vaccine-specific antibody and an increased susceptibility to certain vaccine-preventable diseases. A simple revaccination schedule is warranted. Fifty-nine children (age, 1-18 years) who had completed standard chemotherapy in accordance with Medical Research Council of United Kingdom protocols were recruited. All children received a single dose of Haemophilus influenzae type b (Hib), tetanus, diphtheria, acellular pertussis, meningococcus C, polio, measles, mumps, and rubella vaccines > or = 6 months after completion of treatment. Antibody concentrations were measured before vaccination and 2-4 weeks and 12 months after vaccination. Prevaccination antibody levels were protective for all patients for tetanus (geometric mean concentration [GMC], 0.13 IU/mL; 95% CI, 0.1-0.17 IU/mL), for 87% for Hib (GMC, 0.5 microg/mL; 95% CI, 0.37-0.74 microg/mL), for 71% for measles (GMC, 301 mIU/mL; 95% CI, 163-557 mIU/mL), for 12% for meningococcus C (geometric mean titer [GMT], 1:2.9; 95% CI, 1:2.2 to 1:3.9), and for 11% for all 3 poliovirus serotypes. Revaccination resulted in a significant increase in levels of antibody to each vaccine antigen, with 100% of patients achieving optimal antitetanus antibody concentrations (defined as > 0.1 IU/mL; 1.5 IU/mL; 95% CI, 1.1-2.1 IU/mL), 93% achieving optimal antibody concentrations to Hib (defined as > 1.0 microg/mL; 6.5 microg/mL; 95% CI, 5.1-8.2 microg/mL), 94% achieving optimal antibody concentrations to measles (defined as > or = 120 mIU/mL; 2720 mIU/mL; 95% CI, 1423-5198 mIU/mL), 96% achieving optimal antibody concentrations to meningococcus C (defined as > or = 1:8; 1:1000; 95% CI, 1:483-1:2064), and 85% achieving optimal antibody concentrations to all the 3 poliovirus serotypes (defined as > or = 1:8). For the majority of subjects, protection persisted for at least 12 months after vaccination. Revaccination of children after standard chemotherapy is important, and protection can be achieved in the majority of these children using a simple schedule of 1 vaccine dose at 6 months after completion of leukemia therapy.
    Clinical Infectious Diseases 04/2007; 44(5):635-42. DOI:10.1086/511636 · 9.42 Impact Factor
  • Soonie R Patel, Rudy U Ridwan, Miguel Ortín
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    ABSTRACT: Cytomegalovirus (CMV) disease is an important infectious complication after allogeneic hemopoietic progenitors transplant (HPT), but few data are available in children. To investigate the factors influencing CMV reactivation, subsequent relapses of positive antigenemia, and the development of organ disease in children, the authors retrospectively analyzed 108 children who received allogeneic HPT for malignant conditions at one center. Of these, 41 were CMV serology positive (donor or recipient) before HPT. All those with CMV-positive serology received high-dose acyclovir in conjunction with weekly CMV phosphoprotein-pp65 antigen monitoring of the peripheral blood during the first 3 months. Those with CMV reactivation (positive antigenemia) received preemptive treatment with ganciclovir and/or foscarnet to prevent CMV disease. The incidence of positive antigenemia in this cohort was 41.5% at a mean of 44 +/- 31.6 days after HPT. Two patients (4.9%) subsequently developed late CMV disease. Recipient CMV status was significantly (P = 0.0001) more relevant to reactivation than donor status. Reactivations were significantly more common in single recipient seropositive than double (donor and recipient) positive pairs (P = 0.05). Reactivations were significantly more common in recipients of unrelated donor grafts than matched-related donor grafts (P = 0.025). Reactivations also occurred significantly more in T-cell-depleted graft recipients (P = 0.004) than recipients of unmanipulated grafts. The subsequent development of disease was more common in a CMV-seropositive recipient receiving a CMV-seronegative, T-cell-depleted, unrelated donor graft, and after transplantation receiving treatment for acute graft-versus-host disease. Patients with identified high risk factors for CMV reactivation and disease should be monitored by CMV PCR, and early preemptive treatment should be instigated to prevent the development of disease.
    Journal of Pediatric Hematology/Oncology 09/2005; 27(8):411-5. · 0.96 Impact Factor
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    ABSTRACT: The aim of this retrospective study conducted between H.U. Marques de Valdecilla (Spain) and the Royal Marsden NHS Trust (UK) was to analyse the outcome of patients who underwent haemopoietic progenitor cell transplantation (HPCT) after a previous history of Invasive fungal infections (IFI). This study includes 27 patients (15 autologous, 12 allogeneic). The diagnosis of IFI was microbiologically proven in 21 cases and only radiologically in six. Pre-HPCT treatment included intravenous antifungals in all and surgical excision in eight cases. All patients received post-HPCT antifungal prophylaxis. Median time from diagnosis of IFI to HPCT was 131 days. At median follow-up of 193 days, three patients (two allogeneic, one autologous) had relapse of IFI resulting in death in all cases. One of them had received TBI and two were receiving treatment for graft versus host disease. Each patient was receiving a different form of prophylaxis. Overall, seven patients are alive and disease-free. Ten patients died from disease progression and 10 from transplant-related toxicity, including IFI. In our experience, the risk of post-HPCT reactivation of a previous IFI is low (11%), so IFI should not be an absolute contraindication for HPCT. The combination of aggressive antifungal treatment for IFI and antifungal prophylaxis throughout HPCT reduces the probability of reactivation.
    Leukemia and Lymphoma 09/2005; 46(8):1143-50. DOI:10.1080/10428190500097052 · 2.61 Impact Factor
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    ABSTRACT: Graft failure, regimen-related toxicity and graft-versus-host disease (GVHD) are the critical barriers to unrelated donor transplants for aplastic anaemia (AA). We investigated the use of a novel conditioning regimen consisting of alemtuzumab (humanized CD52 antibody), fludarabine and cyclophosphamide in seven patients with AA, who underwent bone marrow transplant procedure using matched unrelated donors. The aetiology of AA was acquired (n=3), Fanconi's (n=3) and congenital (n=1). Median age was 13 years (range 8-35). All the donors were fully matched for HLA class I and II antigens using high-resolution typing. All the patients engrafted at a median of 18 days (range 13-35). Two patients died of transplant-related complications: one of adenovirus disease and the other developed extensive chronic GVHD of skin followed by cytomegalovirus (CMV) disease. Three patients developed Grade II acute GVHD disease (GVHD); none had Grade III-IV acute GVHD. Of the six evaluable patients, only one developed chronic GVHD. We conclude that this conditioning regimen for unrelated donor transplants for AA is sufficiently immunosuppressive to allow stable engraftment and appears to have a favourable impact on the incidence and severity of GVHD, warranting further investigation.
    Bone Marrow Transplantation 04/2005; 35(5):467-71. DOI:10.1038/sj.bmt.1704799 · 3.47 Impact Factor
  • Soonie R Patel, Miguel Ortín
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    ABSTRACT: Primary varicella-zoster virus (VZV) infection and herpes zoster are important infectious complications after an allogeneic hemopoietic progenitors transplant (HPT). The authors describe a girl with second relapse of acute lymphoblastic leukemia who received an HPT at age 13 years. Two years after the HPT she started a revaccination program of routine childhood vaccines. With each course of vaccines she developed herpes zoster of the C6 dermatome, initially with the rash and later zoster sine herpete. The vaccinations appear to have triggered VZV reactivation by vaccine-induced immunomodulation in this HPT recipient.
    Journal of Pediatric Hematology/Oncology 03/2005; 27(2):106-8. DOI:10.1097/01.mph.0000153442.42030.74 · 0.96 Impact Factor
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    M Ortín
    Annals of Oncology 02/2005; 16 Suppl 2:ii53-62. DOI:10.1093/annonc/mdi715 · 6.58 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2005; 11(2):34-35. DOI:10.1016/j.bbmt.2004.12.100 · 3.35 Impact Factor
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    ABSTRACT: Between August 1989 and November 2003, 33 patients at our center with acquired aplastic anemia underwent bone marrow transplantation (BMT) from HLA-identical sibling donors with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies (MoAb) for conditioning. The median age at BMT was 17 years (range, 4-46 years). Before BMT, 58% were heavily transfused (>50 transfusions), and 42% had previously experienced treatment failure with antithymocyte globulin-based immunosuppressive therapy. Unmanipulated bone marrow was used as the source of stem cells in all patients except 1. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine alone in 19 (58%) patients; 14 received anti-CD52 MoAb in addition to cyclosporine. The conditioning regimen was well tolerated without significant acute toxicity. Graft failure was seen in 8 patients (primary, n = 4; secondary, n = 4). Of those whose grafts failed, 4 survived long-term (complete autologous recovery, n = 2; rescue with previously stored marrow, n = 1; second allograft, n = 1). The cumulative incidence of graft failure and grade II to IV acute and chronic GVHD was 24%, 14%, and 4%, respectively. None developed extensive chronic GVHD. With a median follow-up of 59 months, the 5-year survival was 81% (95% confidence interval, 68%-96%). No unexpected early or late infectious or noninfectious complications were observed. We conclude that the conditioning regimen containing cyclophosphamide and anti-CD52 MoAb is well tolerated and effective for acquired aplastic anemia with HLA-matched sibling donors. The favorable effect on the incidence and severity of GVHD is noteworthy in this study and warrants further investigation.
    Biology of Blood and Marrow Transplantation 12/2004; 10(12):867-76. DOI:10.1016/j.bbmt.2004.09.001 · 3.35 Impact Factor
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    ABSTRACT: A relationship between dose of granulocyte colony-stimulating factor (G-CSF) and maturational stage of the progenitors mobilized in healthy adult donors has been suggested. In this study we characterize the progenitors mobilized by 2 different dosages of G-CSF in children receiving autologous grafts after intensive treatment for solid tumors.
    Haematologica 08/2004; 89(7):881-2. · 5.87 Impact Factor
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    ABSTRACT: Thalidomide was used to treat acute (n=21) or chronic (n=59) graft-vs-host disease (GVHD) in 80 haematopoietic stem cell allograft recipients after failure to respond to the combination of cyclosporine and corticosteroids with or without other agents. The median time to onset of acute GVHD was 11 days, and thalidomide was started at a median of 48 days post transplant. In addition to corticosteroids and cyclosporine, 13 patients had also received other agents before thalidomide. None of the patients responded and all died of acute GVHD. For chronic GVHD (limited in 13, extensive in 46), thalidomide was started at a median of 385 days post transplant. In addition to corticosteroids and cyclosporine, 34 patients received azathioprine concomitantly. In all patients, thalidomide was added to the ongoing immunosuppressive regimen. The median duration of therapy with thalidomide was 60 days (range, 11-1210; <2 weeks in 11). In total, 13 patients (22%) had complete response, eight (14%) partial response and 38 (64%) no response. Response rates were comparable for limited (39%) and extensive (33%) chronic GVHD. At a median of 53 months, 19 patients are alive, 13 without evidence of chronic GVHD. Survival was significantly better in patients who responded to thalidomide. The principal causes of death were progressive chronic GVHD (n=29) and relapsed leukaemia (n=7). In conclusion, thalidomide has no activity in acute GVHD, but has some activity in chronic GVHD in combination with other agents.
    Bone Marrow Transplantation 07/2003; 32(2):165-70. DOI:10.1038/sj.bmt.1704033 · 3.47 Impact Factor
  • Annals of Pharmacotherapy 10/2002; 36(9):1480-1. · 2.92 Impact Factor
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    ABSTRACT: Twenty-one paediatric patients (11 males and 10 females) received a CD34-selected partially matched related donor transplant for malignant (16 cases) and non-malignant conditions (five cases). The average cell dose was 11.13 x 10(6)/kg. Fifteen of 16 patients with malignant conditions and one with non-malignant disease received total body irradiation plus cyclophosphamide. Three of 5 patients with non-malignant conditions and one with leukaemia, received busulphan plus cyclophosphamide. One patient with Fanconi anaemia received 100 mg/kg of cyclophosphamide. Fludarabine (25 mg/m(2)/day for 5 days) was administered prior to all these regimens. Additionally, anti-lymphocyte gamma-globulin (12.5 mg/kg/day) was administered from day -2 to day +2. Three (15%) patients failed to achieve complete chimaerism (CC). These patients received a second cell infusion. Two of them achieved CC. In the third patient, the percentage of donor cells was increased. The likelihood for engraftment was not related to the cell dose received. Acute graft-versus-host disease (GVHD) occurred in nine patients but only one developed GVHD >grade II. Eight patients developed active viral infections, which resolved after treatment. Patients receiving cell doses higher than our average had a significantly faster CD3 and CD4 cell recovery and experienced a lower incidence of viral infections. After 480 +/- 255 days of median follow-up, 16/21 patients are alive and well and have CC. Three patients died of leukaemic relapse and a fourth from progression of his disease (adreno-leuko-dystrophy). We conclude that partially matched related donors are a feasible source of haemopoietic progenitor cells for transplantation for patients without matched familial or unrelated donors.
    Bone Marrow Transplantation 10/2002; 30(6):359-66. DOI:10.1038/sj.bmt.1703667 · 3.47 Impact Factor

Publication Stats

248 Citations
58.25 Total Impact Points


  • 2012
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2005
    • The Royal Marsden NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2002
    • Birmingham Children's Hospital NHS Foundation Trust
      • Department of Oncology & Haematology
      Birmingham, England, United Kingdom