A Feasibility Study of the Full Outpatient Conduction of Hematopoietic Transplants in Persons with Multiple Sclerosis Employing Autologous Non-Cryopreserved Peripheral Blood Stem Cells.

BACKGROUND: With the goal of achieving immune system reset, autologous hematopoietic stem cell transplantations have been performed in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Two hundred and eighty-six consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSCs), on an outpatient basis and conditioning with cyclophosphamide and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217. RESULTS: One hundred and ninety-four females and 92 males were included; the median age was 47. All procedures were started on an outpatient basis and only 8 persons needed to be admitted to the hospital during the procedure. In order to obtain at least 1 × 106/kg viable CD34 cells, 1-4 aphereses were performed (median 1). The total number of viable CD34+ cells infused ranged between 1 and 19.2 × 106/kg (median 4.6). Patients recovered above 0.5 × 109/L absolute granulocytes on median day 8 (range 0-12). Two individuals needed red blood cells but none needed platelet transfusions. There were no transplant-related deaths and the 128-month overall survival of the patients is 100%. In 82 persons followed up for 3 or more months, the Expanded Disability Status Scale diminished from a mean of 5.2-4.9, the best results being obtained in relapsing-remitting and primary progressive MS. CONCLUSIONS: It is possible to conduct autotransplants for patients with MS employing non-frozen PBSCs and outpatient conduction. Additional information is needed to assess the efficacy of these procedures in the treatment of patients with MS.

HB Fannin-Lubbock-I with a single GGC>GAC mutation at beta119(GH2)Gly-->Asp in a homozygous Mexican patient.

We studied a fast-moving, abnormal hemoglobin (Hb) identified as Fannin-Lubbock-I [beta119(GH2)Gly-->Asp] in a homozygous Mexican girl. To date, homozygosity for the Hb Fannin-Lubbock-I variant has not been reported. Her parents and five other relatives were heterozygotes. The 5' beta-globin haplotype analysis showed that the mutation was associated with haplotype 2 [- + + - +]for the epsilon, (G)gamma, (A)gamma, 5' and 3 'psibeta-globin sites, and also segregated with the TGTTC haplotype, which was constructed with five polymorphic sites of the beta-globin gene [exon 1-nucleotide (nt) 6 (C>T) and IVS-II-16 (C>G), IVS-II-46 (T>C), IVS-II-74 (G>T), and IVS-II-81 (C>T). In 1994, a variant with an additional mutation at codon 111 [beta111(G13)Val-->Leu] was described in five Spanish families. This variant was termed Hb Fannin-Lubbock-II, and the question of the existence of Hb Fannin-Lubbock-I arose. However, based on our findings, we were able to confirm the existence of Hb Fannin-Lubbock-I and propose that this mutation has a different origin from the one identified in Spanish families.

Molecular characterization of alpha-thalassemia in the Mexican population.

BACKGROUND: alpha-Thalassemia (alpha-Thal) has been poorly characterized at the molecular level in Mexico. METHODS: 106 consecutive individuals identified in Laboratorios Clínicos de Puebla, with either hypochromia (MCH < 24 pg) and/or microcytosis (MCV < 75 fl in women or < 80 fl in man), without iron deficiency, with or without anemia were investigated in this study, along a 16 month-period. alpha and beta-Thal were looked for, the former were characterized at the molecular level. RESULTS: Out of the 106 consecutive cases with hypochromia and/or microcytosis and normal levels of protoporphyrin zinc complex, 48 cases (45.3%) had thalassemia (37 cases of betaThal and 11 cases of alphaThal), whereas in 58 cases (54.7%) a definite diagnosis could not be established. Of the alpha-Thal cases, 8 were heterozygous and two were homozygous for the -alpha3.7 deletion, whereas one case was heterozygous for the alpha2Hph allele. CONCLUSIONS: Only few of the alpha-Thal alleles tested were found, thus the alpha-thalassemic mutations, present in the studied population, seem to be rather heterogeneous.

Molecular characterization of alpha-thalassemia in the Mexican population / Caracterización molecular de talasemia alfa en una población mexicana

Background. α-Thalassemia (α-Thal) has been poorly characterized at the molecular level in Mexico. Methods. 106 consecutive individuals identified in Laboratorios Clínicos de Puebla, with either hypochromia (MCH < 24 pg) and/or microcytosis (MCV < 75 fl in women or < 80 fl in man), without iron deficiency, with or without anemia were investigated in this study, along a 16 month-period, α and β-Thal were looked for, the former were characterized at the molecular level. Results. Out of the 106 consecutive cases with hypochromia and/or microcytosis and normal levels of protoporphyrin zinc complex, 48 cases (45.3%) had thalassemia (37 cases of β-Thal and 11 cases of α-Thal), whereas in 58 cases (54.7%) a definite diagnosis could not be established. Of the α-Thal cases, 8 were heterozygous and two were homozygous for the -α3.7 deletion, whereas one case was heterozygous for the α2Hph allele. Conclusions. Only few of the α-Thal alleles tested were found, thus the α-thalassemic mutations, present in the studied population, seem to be rather heterogeneous.

Antecedentes. En México, la α-talasemia (α-Thal) ha sido pobremente caracterizada a nivel molecular. Mátodos. Se estudiaron 106 individuos consecutivos identificados en los Laboratorios Clínicos de Puebla, con hipocromia (CMH < 24 pg) y lo microcitosis (VCM < 75 fl en mujeres o 80 fl en hombres), sin deficiencia de hierro, con o sin anemia, durante un periodo de 16 meses. Se investigaron α y β-Thal; las primeras fueron caracterizadas a nivel molecular. Resultados. De los 106 casos consecutivos estudiados con hipocromia y/o microcitosis, y niveles normales del complejo de protoporfirina-cinc, 48 casos (45.3%) tenían talasemias (37 de ellos β-Thal y 11 α-Thal), mientras que en 58 casos (54.7%) no pudo establecerse un diagnóstico definitivo. De las talasemias α, ocho casos eran heterocigotos y dos homocigotos para la deleción -α3.7, mientras que sólo un caso resultó heterocigoto para el alelo α2Hph. Conclusiones. De los alelos α-Thal estudiados sólo se encontraron algunos, de lo que se infiere que en la población estudiada esas mutaciones parecen ser bastante heterogáneas.

Hemoglobinas anormales y talasemias en la República Mexicana / Abnormal hemoglobins and thalassemias in Mexico

La información en México sobre las anormalidades estructurales y de síntesis de la hemoglobina es resultado de encuestas y del estudio de pacientes que sufren anemia hemolítica. En población indígena se han estudiado varios miles de personas y concluído que las hemoglobinas anormales se encuentran virtualmente ausentes en indígenas puros y que los hallazgos esporádicos de Hb S identificados entre ellos se deben a mezcla con africanos atraídos a México como esclavos durante la colonia. En población indígena se han identificado dos nuevas variantes: la Hb México y la Hb Chiapas. En las encuestas en población híbrida de diversas regiones del país destaca que en ciertas regiones de las costas occidental y oriental de la república, se observa una frecuencia variable de terocigotos de Hb S y que en algunas poblaciones se han encontrado prevalencias elevadas de portadores de Hb S, semejantes a las encontradas en algunas regiones de Africa. En 200 sujetos estudiados en una población de la costa del Golfo de México (Tamiahua, Veracruz) se identificaron 6 por ciento de heterocigotos de Hb S y 15 por ciento de portadores de talasemia beta. Esta asociación explica por qué se han encontrado varios heterocigotos dobles de Hb S y talasemia beta, en esa zona del país. En 12,154 adultos estudiados en población hospitalaria de Guadalajara y puebla, se encontraron otras variantes hemoglobínicas anormales como C, SC, Riyadh, Baltimore, Tarrant, Fannin-Lubbock y México. La encuesta de una comunidad de origen italiano vecina a la ciudad de Puebla, mostró 1.3 por ciento de portadores de talasemia beta, frecuencia similar a la observada en las regiones de Italia de donde provinieron los ancestros de los act7uales pobladores. Estudiando sujetos afectados de anemia hemolítica se han identificado Hb I-Filadelfia, Hb G-San José y Hb D-Los Angeles. Por lo que hace a talasemias y síndromes talasemicos, puede afirmarse que talasemia es la anormalidad más frecuente de la hemoglobina en la población seleccionada de la república mexicana. Una revisión efectuada en nuestro laboratorio mostró que el 75 por ciento de las anormalidades de la hemoglobina corresponden a sujetos heterocigoto para talasemia beta...

Two cases of hypergranular acute lymphoblastic leukemia

Se presentan dos casos de pacientes con leucemia aguda linfoblástica hipergranular, una forma infrecuente de leucemia que en poblaciones caucásicas corresponde del 2 al 7 por ciento de leucemias linfoblásticas de niños y adultos. Los dos casos representan el 1.4 por ciento de las leucemias linfoblásticas estudiadas y tratadas en una sola institución en un lapso de 12 años. En ambos casos las células malignas tuvieron marcadores de células B tempranas, expresando los antígenos CD45, Cd10 y CD19 y los gránulos fueron positivos a la reacción de PAS. Los dos pacientes fallecieron poco después de haberse iniciado el tratamiento antileucémico. Parece que esta forma infrecuente de leucemia linfoblástica es más rara en mestizos mexicanos que en sujetos caucásicos. Se ha descrito previamente un pronóstico sombrio en pacientes con este tipo de leucemia