Asunto(s)
Leucemia Mieloide Aguda/terapia , Oclusión Vascular Mesentérica/etiología , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Adulto , Enfermedad Injerto contra Huésped/complicaciones , Humanos , Masculino , Venas Mesentéricas/patología , Trasplante Homólogo/efectos adversosAsunto(s)
Deleción Cromosómica , Cromosomas Humanos Y , Leucemia Mieloide Aguda/genética , Trasplante de Células Madre , Donantes de Tejidos , Quimera por Trasplante/genética , Adulto , Femenino , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/terapia , Masculino , Quimera por Trasplante/sangre , Trasplante HomólogoRESUMEN
Graft rejection is a major cause of treatment failure after T-cell-depleted stem cell transplantation (TCD-SCT) and remains a therapeutic challenge. Donor leukocyte infusions (DLIs) have an efficient graft versus host effect, which has been successfully used to treat recipient relapses. We hypothesized that this effect could be exploited to counteract the host versus graft reactions responsible for graft rejection. We report two adult patients with haematological malignancies who underwent sex-mismatched TCD-SCT from HLA-identical sibling donors. Peripheral blood (PB) counts and bone marrow (BM) cellularity were studied on a serial basis. Sequential chimaerism and minimal residual disease analysis were performed by FISH on PB and BM samples as well as on leukocyte lineages (T and B lymphocytes and myeloid cells) purified from PB using immunomagnetic technology. Both patients were diagnosed with incipient graft rejection 2-3 months after engraftment, based on persistently decreasing PB counts and BM cellularity together with the observation of decreasing mixed chimaerism (increasing percentage of recipient cells), mostly in whole PB and T lymphocytes. Both patients were successfully treated with a single DLI (1 x 10(7) CD3+ cells/kg), thereafter achieving normal PB counts and BM cellularity as well as complete chimaerism. Interestingly, the only side effect observed was mild graft versus host disease that did not require treatment. In conclusion, provided that an early diagnosis is made, the graft versus host lymphohaemopoietic effect harboured by immunocompetent donor cells can be successfully used for the treatment of incipient graft rejection.
Asunto(s)
Rechazo de Injerto/terapia , Enfermedad Injerto contra Huésped , Transfusión de Leucocitos/métodos , Leucocitos/citología , Leucocitos/metabolismo , Antígenos CD34/biosíntesis , Antígenos CD34/metabolismo , Médula Ósea/metabolismo , Complejo CD3/biosíntesis , Trasplante de Células , Femenino , Factor Estimulante de Colonias de Granulocitos/metabolismo , Histocompatibilidad , Humanos , Inmunosupresores/farmacología , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Hermanos , Trasplante de Células Madre , Factores de Tiempo , Trasplante Homólogo , Trasplantes , Resultado del TratamientoRESUMEN
A randomised trial in breast cancer patients was designed to compare the number of peripheral blood progenitor cells collected after mobilisation with a single dose of 10 microg/kg/day granulocyte colony-stimulating factor (G-CSF) (n=14) or a split dose of 5 microg/kg twice daily (n=14). Both groups were well balanced. No significant differences were observed between groups regarding aphereses parameters. The total number of CD34+ cells collected was higher in the split-dose group (mean of 7.1 and median of 7.4 x 10(6)/kg) than in the single-dose group (5.6 and 5.8 x 10(6)/kg, respectively) (P=0.26). The mean of CD34+ cells collected after the first apheresis procedure was 3.9 x 10(6)/kg for the split dose group and 3.1 x 10(6)/kg for the single-dose group (P=0.24). Circulating CD34+ cells before the first apheresis were higher for the split-dose group (mean 79.7 vs 59.2 x 10(6)/l) (P=0.14). All bone pain scores applied were significantly higher for the split-dose group. Our primary end point of improving the mean of total CD34+ cells collected to 2.5 x 10(6)/kg was not achieved with twice-daily G-CSF administration. Further studies evaluating different mobilisation schedules with G-CSF are needed to determine the optimal regimen.
Asunto(s)
Neoplasias de la Mama/terapia , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Adulto , Antígenos CD34/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recuento de Células , Relación Dosis-Respuesta a Droga , Femenino , Supervivencia de Injerto , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Factor Estimulante de Colonias de Granulocitos/farmacocinética , Movilización de Célula Madre Hematopoyética/efectos adversos , Humanos , Leucaféresis , Persona de Mediana Edad , Dolor/inducido químicamente , Trasplante de Células Madre de Sangre Periférica/métodos , Trasplante AutólogoRESUMEN
Patients that receive a T-cell depleted (TCD) hematopoietic stem cell transplantation (SCT) show higher risk of graft failure/rejection and of disease relapse than those that receive unmanipulated grafts. The purpose of the present investigation was to analyze the usefulness of chimaerism quantification in bone marrow (BM), peripheral blood (PB), and leukocyte lineages such as T lymphocytes (CD3+,both CD4+ and CD8+), B lymphocytes (CD19+) and myeloid cells (CD15+), for the early detection of graft failure/rejection episodes and disease relapse after TCD-PBSCT. Two of the ten (2/10) patients included in the study showed stable complete chimaerism (CC). The other 8/10 patients showed decreasing mixed chimaerism (MC) and 7 of them had either graft failure (n = 1)/rejection (n = 3) or disease relapse (n = 3). In two patients relapsed from chronic myeloid leukemia, MC was observed in BM and PB, with higher percentages of autologous cells in BM, as well as in leukocyte lineages, with higher percentages of recipient cells in the myeloid lineage than in lymphocytes. Combined analysis of chimaerism and minimal residual disease allowed early diagnosis of relapse and successful rescue therapy with donor leukocyte infusions (DLI), before the onset of hematological relapse. Chimaerism analysis allowed early diagnosis of incipient graft rejection in 3 patients. These patients showed MC both in BM and PB, with greater percentages of recipient cells in PB. Analysis of leukocyte lineages showed higher percentages of autologous cells in T lymphocytes (mainly CD8+) than in B or myeloid cells. Two of these patients were successfully treated with DLI and recovered normal PB counts and BM cellularity, as well as CC. The graft versus recipient hemopoiesis effect harbored by the donor immunocompetent cells infused seems useful forthe treatment of graft rejection, provided that an early diagnosis is made.
Asunto(s)
Trasplante de Células Madre de Sangre Periférica , Linfocitos T/citología , Adulto , Antígenos CD19/biosíntesis , Complejo CD3/biosíntesis , Antígenos CD4/biosíntesis , Antígenos CD8/biosíntesis , Linaje de la Célula , Femenino , Rechazo de Injerto/prevención & control , Humanos , Hibridación Fluorescente in Situ , Leucocitos/citología , Antígeno Lewis X/biosíntesis , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Recurrencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Quimera por TrasplanteRESUMEN
An in utero paternal CD34(+) cell transplant was performed in a T-B+NK+ SCID fetus. We report here the results of the 3-year humoral immune reconstitution study. The methods used were ApoB VNTR typing, flow cytometry, nephelometry, hemagglutination, ELISA, ELISPOT and lymphoproliferative assays. The T cells were of donor origin whereas monocytes, B and NK cells were of host origin. Peripheral B cell counts and IgM levels were normal since birth. IVIG therapy was required at 5 months of age until 2 years old. IgA levels > or =20 mg/dl were detected from month 17 post transplantation. Isohemagglutinins were present since month 8 post transplantation, the highest titers (anti-A:1/128, anti-B:1/32) were obtained at month 33 post-transplantation. After immunization with rHBsAg, circulating anti-HBsAg IgG secreting cells and a 7.8-fold increase in serum anti-HBsAg Ab were detected. We conclude that split chimerism following in utero haploidentical BMT allows complete humoral immune reconstitution in a T-B+NK+ SCID patient.
Asunto(s)
Linfocitos B/inmunología , Trasplante de Médula Ósea/métodos , Enfermedades Fetales/terapia , Inmunodeficiencia Combinada Grave/terapia , Quimera por Trasplante/inmunología , Formación de Anticuerpos , Apolipoproteínas B/genética , Linfocitos B/citología , Biomarcadores , Linaje de la Célula , Consanguinidad , Padre , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/embriología , Enfermedades Fetales/genética , Estudios de Seguimiento , Supervivencia de Injerto , Haplotipos/genética , Histocompatibilidad , Humanos , Inmunoglobulina A/biosíntesis , Inmunofenotipificación , Recién Nacido , Donadores Vivos , Masculino , Repeticiones de Minisatélite , Diagnóstico Prenatal , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/embriología , Inmunodeficiencia Combinada Grave/genética , Subgrupos de Linfocitos T/citología , Subgrupos de Linfocitos T/inmunología , VacunaciónRESUMEN
A 154-bp PCR product amplified from human female DNA mapped onto the Y chromosome under high-stringency in situ hybridization conditions. The female DNA sequence revealed an 89% homology with the HSDYZ1 sequence. When the same primers were used to amplify male DNA, a 154-bp DNA fragment was also obtained, showing a 98% homology with HSDYZ1. However, although the HSDYZ1 sequence is widely distributed along the long arm of the Y chromosome, both of these particular PCR products are di-regionally localized within this distal block of constitutive heterochromatin. In situ hybridization under lower stringency showed that these 154-bp sequences map both onto the autosomes and the Y chromosome. Overall, this paper shows (i) a new class of DNA sequences shared by the autosomes and the Y chromosome; and (ii) a substructured organization of some DNA repeats within the DYZ1 family that forms a large part of the constitutive heterochromatin of the Y chromosome.
Asunto(s)
Cromosomas Humanos/genética , Cromosoma Y/genética , Mapeo Cromosómico , Cartilla de ADN , Femenino , Heterocromatina/genética , Humanos , Hibridación Fluorescente in Situ , Masculino , Reacción en Cadena de la PolimerasaRESUMEN
Of the subtypes of acute lymphoblastic leukemia (ALL), the "common" subtype (c-ALL) bears the best prognosis. Nevertheless, there has been no report of cytologic criteria that can distinguish c-ALL from the B-cell (B-ALL) and T-cell (T-ALL) subtypes. We present a case of c-ALL with relapse, with cytochemical and immunocytochemical as well as cytologic studies. Certain cytologic observations in this case could serve to differentiate c-ALL from B-ALL and T-ALL; the morphologic criteria suggested have been seen by us in other c-ALL cases. We think they will be useful in future fine needle aspiration studies in order to demonstrate extramedullary relapses as well as to differentiate ALL subtypes without the need of more costly immunologic studies.
Asunto(s)
Leucemia Linfoide/diagnóstico , Anticuerpos Monoclonales , Antígenos de Neoplasias/análisis , Niño , Humanos , Técnicas para Inmunoenzimas , Leucemia Linfoide/inmunología , Leucemia Linfoide/patología , Masculino , Testículo/patologíaRESUMEN
We report a case, in a 74-year-old man, of chronic myelomonocytic leukemia (CMML) that showed cutaneous involvement in its terminal phase. The patient developed a nodular eruption with an irregular distribution over the entire skin surface. Histology showed an acute leukemic infiltration in the reticular dermis. We were able to demonstrate cells with intermediate myeloid and monocytic characteristics ("paramyeloid cells") in the skin biopsy and in bone marrow smears. There have been only four patients reported previously with similar clinical findings. In one of them the cutaneous eruption heralded an aggressive clinical shift of the disease, as in our case. The present case confirms the utility of skin biopsy in similar cases for predicting the evolution of the disease.