Cord blood banking and transplantation at the Mexican Institute of Social Security: the first 5 years.

BACKGROUND: In January 2005, the Cord Blood Bank (CBB) at the Mexican Institute of Social Security initiated activities. Herein, we describe the experience generated during this period (January 1, 2005-December 31, 2009). STUDY DESIGN AND METHODS: Good manufacturing practices and standard operating procedures were used to address donor selection, as well as umbilical cord blood (UCB) collection, processing, and cryopreservation. Based mainly on HLA and nucleated cell content, specific UCB units were thawed, processed, and released for transplantation. RESULTS: A total of 589 UCB units were stored, representing 54% of the total number of units collected. Forty-eight units (8.14% of the stored units) were released for transplantation of 36 patients. Twenty-six patients (72% of cases) corresponded to patients with acute leukemia, five (14%) to patients with marrow failure, and the rest (five; 14%) to patients with hemoglobinopathies and other syndromes. The median number of nucleated cells infused per patient was 6.71 × 10(7) /kg and the median number of CD34+ cells was 4.8 × 10(5) /kg. Current engraftment data indicate that engraftment occurred in 56%, and no engraftment in 44%, of cases. Engraftment was more frequent (59%) in patients that received more than 3 × 10(7) total nucleated cells (TNCs)/kg body weight, than in those receiving fewer than 3 × 10(7) TNCs/kg (40%). Myeloid engraftment was observed 7 to 54 days posttransplant (median, 23 days), whereas platelet engraftment was detected on Days 12 to 87 posttransplant (median, 38 days). To date, the disease-free survival rate was 41% and the overall survival was 47%, with survival periods of 126 to 1654 days. CONCLUSION: Although the experience presented herein is still limited and the period of analysis is still short, the results obtained during these 5 years are encouraging.

Establishing a cord blood banking and transplantation program in Mexico: a single institution experience.

BACKGROUND: Over the past decade, umbilical cord blood (UCB) banking and transplantation have increased significantly worldwide. The experience in developing countries, however, is still limited. In January 2005 the Mexican Institute of Social Security (IMSS) initiated its UCB banking and transplantation program. This study reports on the experience generated at this institution during the first 2 years of activities. STUDY DESIGN AND METHODS: A public UCB bank was established at La Raza Medical Center, IMSS, in Mexico City. Good manufacturing practices and standard operating procedures were used to address donor selection, as well as UCB collection, processing, and cryopreservation. Based mainly on human leukocyte antigen (HLA) and total nucleated cell (TNC) content, specific UCB units were thawed, processed, and released for transplantation. RESULTS: Based on stringent selection criteria, 360 UCB units were collected from January 2005 to December 2006. A total of 201 (56%) units (minimum volume, 50 mL without anticoagulant) were processed and stored. Median values for specific parameters were as follows: volume, 89.9 mL; viability, 94.8%; TNCs, 0.91 x 10(9); CD34+ cells, 3.13 x 10(6); and colony-forming cells, 1.20 x 10(6). During this period, 10 units had been released for transplantation to seven patients (six children and one adult). Engraftment was observed in five patients; four of them were still in remission (114-293 days after transplant). In spite of showing sustained engraftment, one patient died on Day +88. Two patients showed no engraftment and died 29 to 30 days after transplant. CONCLUSION: The results obtained during this initial period are encouraging and indicate that the UCB banking and transplantation program at IMSS will help to improve already existing hematopoietic cell transplant programs in Mexico. The experience generated at IMSS may be helpful to other institutions, particularly those in developing countries.

In vitro functional alterations in the hematopoietic system of adult patients with acute lymphoblastic leukemia.

In previous studies, we have demonstrated that progenitor cell-enriched marrow cell populations from patients with myeloid leukemia - including both acute (AML) and chronic (CML) - show severe functional alterations when cultured in stroma-free liquid cultures supplemented with stimulatory cytokines. In trying to expand our characterization of the biology of leukemic cells, in the present study we have used a similar approach and analyzed the in vitro growth of equivalent cell populations from patients with acute lymphoblastic leukemia (ALL). ALL marrow cell populations -enriched for hematopoietic progenitors by means of a negative selection procedure- were assessed for their proliferation and expansion potentials, in liquid cultures supplemented with a mixture of early- and late-acting recombinant stimulatory cytokines, throughout a 25-day culture period. ALL cells, although capable of responding to the stimulatory signals provided by hematopoietic stimulators, showed deficient proliferation potentials (reduced capacity to generate more nucleated cells), as compared with their normal counterparts. The capacity to generate myeloid and erythroid progenitors was also significantly reduced in ALL cultures. Interestingly, the functional alterations observed in ALL cultures (i.e., deficient proliferation and expansion potentials) were more pronounced in those from Ph+ patients than in those from Ph- patients. This study indicates that bone marrow cell populations - enriched for hematopoietic progenitor cells - from ALL patients possess deficient proliferation and expansion potentials in vitro, and that such functional alterations are more severe when cells are derived from Ph+ patients, as compared to their Ph- counterparts.

Deficient proliferation and expansion in vitro of two bone marrow cell populations from patients with acute myeloid leukemia in response to hematopoietic cytokines.

One has previously characterized two different hematopoietic cell populations (obtained by negative-selection) from normal bone marrow. Population I was enriched for CD34+ Lin- cells, whereas Population II was enriched for CD34+ CD38- Lin- cells. Both populations showed elevated proliferation and expansion potentials in serum-free liquid cultures, supplemented with a combination of eight different cytokines, with the latter displaying more immature features than the former. One has also characterized the chronic myeloid leukemia (CML) counterparts of these two populations and demonstrated functional deficiencies in terms of their growth in culture. In keeping with this line of research, the goal of the present study was to obtain the same two populations (Populations I and II) from acute myeloid leukemia (AML) bone marrow and to characterize their biological behavior under the same culture conditions. The results demonstrated that AML-derived Populations I and II were unable to proliferate in culture conditions that allowed significant proliferation of Populations I and II from normal marrow. Population I from AML also showed a deficient expansion capacity; in contrast, Population II cells were able to expand to a similar extent to the one observed for Population II from normal marrow. Both normal and AML populations were highly sensitive to the inhibitory effects of TNF-alpha; interestingly, whereas in normal fractions TNF-alpha showed a more pronounced inhibitory effect on more mature cells (Population I), this cytokine inhibited proliferation and expansion of AML Populations I and II in a similar degree. It is noteworthy that the functional deficiencies observed in AML cells were even more pronounced than those previously reported for cultures of CML cells. The results reported here may be of relevance considering the interest by several groups in developing methods for the in vitro purging of leukemic cells, as part of protocols for autologous transplantation of hematopoietic cells in leukemic patients.

Functional integrity in vitro of hematopoietic progenitor cells from patients with chronic myeloid leukemia that have achieved hematological remission after different therapeutic procedures.

In this study, we have assessed the in vitro growth of hematopoietic progenitor cells (HPC) from chronic myeloid leukemia (CML) patients that have recovered after different treatments. Bone marrow cells were obtained from 33 CML patients, including patients at diagnosis, before treatment (n=12), and patients that have achieved hematological remission (and in most cases a major cytogenetic response) after different therapeutic procedures (n=21), including patients treated with Interferon-alpha (IFN; n=5), imatinib mesylate (IMATINIB; n=8) and patients that received an allogeneic hematopoietic cell transplant (HCT; n=8). Marrow cells were enriched for CD34(+) cells and cultured in a serum- and stroma-free liquid culture system, supplemented with a combination of 8 recombinant cytokines. Normal samples were studied as controls. HPC from CML patients before therapy showed deficient proliferation and expansion potentials in culture (140-fold increase in nucleated cell number and 1.3-fold increase in colony-forming cell number) as compared to normal progenitors (1200-fold increase in nucleated cell number and 25-fold increase in colony-forming cell number). In contrast, HPC from patients treated with IMATINIB showed growth potentials similar to those of normal progenitors. Progenitors from patients after HCT also showed significant proliferation and expansion capacities. Interestingly, progenitors from IFN-treated patients showed proliferation and expansion kinetics similar to those of cells from untreated patients. These results indicate that, although treatment of CML patients with IFN, IMATINIB or HCT resulted in complete hematological remission (and a major cytogenetic response), only patients treated with IMATINIB and, to a lesser extent, with HCT showed a full hematopoietic recovery, as determined by the in vitro growth of HPC in our culture system.

In vitro proliferation and expansion of hematopoietic progenitors present in mobilized peripheral blood from normal subjects and cancer patients.

In the present study, we have assessed, in a comparative manner, the in vitro proliferation and expansion potentials of hematopoietic progenitor cells (HPC) present in mobilized peripheral blood from normal subjects (MPB-n; n = 18) and cancer patients (MPB-c; n = 18). The latter included patients with breast cancer (BrCa; n = 8), Hodgkin disease (HD; n = 4), non-Hodgkin lymphoma (NHL; n = 3), and acute myeloid leukemia (AML; n = 3). Progenitor cells from normal bone marrow (BM) and umbilical cord blood (UCB) were included as controls. HPC, enriched by a negative selection procedure, were cultured for 25 days, in serum-free liquid media in the presence of a cytokine combination including early- and late-acting cytokines. Our results demonstrate that the in vitro biological properties of progenitor cells present in MPB differ, depending on whether they are derived from healthy individuals, from patients with solid tumors, or from patients with hematological neoplasias. Among all cell sources analyzed, UCB-derived progenitors showed the greatest proliferation and expansion potentials (1000-fold increase in total cell numbers on day 15, and a 22-fold increase in myeloid progenitor cell numbers, at day 10). Progenitor cells present in MPB from hematologically normal individuals showed proliferation and expansion potentials comparable to those of HPC from normal BM (500-fold increase in total cell numbers on day 15, and a 14-fold increase in myeloid progenitor cell numbers, at day 10). The proliferation/expansion potentials of MPB progenitors from BrCa patients were also within the normal range, although in the lower levels (327-fold increase in total cell numbers, on day 15, and 11.8-fold increase in myeloid progenitors, at day 10). In contrast, progenitors present in MPB from patients with HD, NHL, and especially AML, showed reduced in vitro capacities (119-, 102-, and 51-fold increase in total cell numbers, respectively; and 8-, 4-, and 2.6-fold increase in myeloid progenitor cells, respectively). To our knowledge, this is the first report in which the in vitro proliferation and expansion potentials of HPC from MPB from normal subjects and cancer patients are assessed simultaneously in a comparative manner.

Kinetics of hematopoiesis in bone marrow cultures from patients with chronic myeloid leukemia: effect of recombinant cytokines in dexter-type long-term cultures.

Chronic myeloid leukemia (CML) is a hematological neoplasia that results from the transformation of a hematopoietic stem cell. It is characterized by the expansion of the myeloid lineage, which results in the accumulation of mature and immature granulocytes in peripheral blood and bone marrow. However, when CML marrow cells are cultured in Dexter-type long-term cultures (LTMC) hematopoiesis is defective and can be sustained for only a few weeks. One possible explanation for the deficient growth of hematopoietic cells in CML LTMC is that some factors that act as key regulators of hematopoiesis are absent in this experimental system. Thus, we tested this hypothesis by adding recombinant cytokines to these cultures. As a first approach, we added recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), rhGranulocyte-CSF (rhG-CSF) and rhErythropoietin (rhEPO); each factor was added individually once a week. Addition of rhGM-CSF and rhG-CSF resulted in a significant increase in the levels of nucleated cells and myeloid progenitors; the highest effects were seen in the presence of rhGM-CSF. Interestingly, such a cytokine also induced a significant decrease in the levels of erythroid progenitors. Recombinant hEPO had no significant effects on nucleated cells or myeloid progenitors, however, it induced a significant, although transient, increase in the levels of erythroid cells. The above results indicate that the hematopoietic regulators used here (rhGM-CSF, rhG-CSF and rhEPO) are capable of stimulating the growth of hematopoietic cells in LTMC from CML patients. Thus, this study demonstrates that it is, indeed, possible to manipulate CML LTMC by the addition of recombinant cytokines; this observation may be of particular relevance, since this in vitro experimental system has already been used as a method for purging of leukemic cells in autologous transplant settings. By using specific recombinant hematopoietic modulators it might be possible to make LTMC a more efficient system for such a clinical purpose.

High doses of dexamethasone in adult patients with idiopathic thrombocytopenic purpura.

BACKGROUND: High-dose dexamethasone (DXM) has been used in treatment of patients with idiopathic thrombocytopenic purpura (ITP) who are refractory to other treatments such as prednisone and splenectomy; nevertheless, different studies show variable success rates, this postulated as possibly being due to racial differences. The objective of this study was to determine DXM effectiveness at high doses in Mexican mestizo adult patients diagnosed with ITP with and without splenectomy. METHODS: Nonhospitalized adult patients with ITP were included, eight patients previously splenectomized (group 1) and 11 who had not undergone splenectomy (group 2). Patients received DXM 40 mg/day intravenously (i.v.) during 4 consecutive days every 4 weeks until six cycles were completed. RESULTS: There were no differences between the two groups regarding age (mean 39 vs. 33 years of age) and initial platelet count (M 17 vs. 24 x 10(9)/L). Median evolution time was 84 months for group 1 and 7 months for group 2 (p = 0.002). Of 19 patients, nine achieved a favorable response (FR), six belonged to group 1, and three to group 2 (Fisher p = 0.07). Nevertheless, after 6 months only two group 1 patients and two group 2 patients maintained FR (Fisher exact test p = 1). Patients achieving FR to initiation of second cycle maintained FR at the end of six cycles. CONCLUSIONS: Thus, the previously mentioned high-dose DXM therapy appears to be useful for both patients with ITP with and without splenectomy and high-dose DXM appears to be a good alternative therapy for postsplenectomy and relapse patients. However, duration of FR to treatment was brief; therefore, other treatment plans might be required to achieve longer remission duration. Response was similar to that observed in other studies carried out in different populations; thus, apparently no genetic or racial variations exist. In addition, whether patients not responding after second cycle should continue until completing the 6-month plan or should try a different therapeutic approach must be considered in the treatment plan.

Comparative analysis of the in vitro proliferation and expansion of hematopoietic progenitors from patients with aplastic anemia and myelodysplasia.

Aplastic anemia (AA) and myelodysplasia (MDS) show great similarities in their biology. To date, however, it is still unclear to what extent hematopoietic progenitor cells (HPCs) from AA and MDS share biological properties and what the functional differences are between them. In trying to address this issue, in the present study we have analyzed, in a comparative manner, the proliferation and expansion capacities of bone marrow (BM) progenitor cells from AA and MDS in response to recombinant cytokines. BM samples from normal subjects (NBM) and patients with AA and MDS were enriched for HPC by immunomagnetic-based negative selection. Selected cells were cultured in the absence (control) or in the presence of early-acting cytokines (Mix I), or early-, intermediate- and late-acting cytokines (Mix II). Proliferation and expansion were assessed periodically. In NBM and MDS cultures apoptosis was also determined. In NBM cultures, Mix I induced a nine-fold increase in total cell numbers and a 3.6-fold increase in colony-forming cell (CFC) numbers. In Mix II-supplemented cultures, total cells were increased 643-fold, and CFC 12.4-fold. In AA cultures, no proliferation or expansion were observed in Mix I-supplemented cultures, whereas only a four-fold increase in total cell numbers was observed in the presence of Mix II. In MDS cultures, a 12-fold increase in total cells and a 2.9-fold increase in CFC were observed in the presence of Mix I; on the other hand, Mix II induced a 224-fold increase in total cells and a 5.9-fold increase in CFC. Apoptosis was reduced in cytokine-supplemented cultures from NBM. In contrast, Mix II induced a significant increase in the rate of apoptosis in MDS cultures. Our results demonstrate that, as compared to their normal counterparts, AA and MDS progenitors are deficient in their proliferation and expansion potentials. Such a deficiency is clearly more pronounced in AA cells, which seem to be unable to respond to several cytokines. MDS progenitors, on the other hand, are capable to proliferate and expand in response to cytokines; however, their rate of apoptosis is increased by intermediate- and late-acting cytokines, so that the overall proliferation and expansion are significantly lower than those of normal progenitor cells.

Effect of rhGM-CSF on the kinetics of hematopoiesis in long-term marrow cultures from patients with acute myelogenous leukemia.

In the present study, we have assessed the effects of recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (rhGM-CSF) in Dexter-type long-term marrow cultures (LTMC) from patients with acute myelogenous leukemia (AML). Addition of rhGM-CSF to AML LTMC resulted in a significant increase in the number of total nucleated cells (1.3-4.3-fold, as compared to untreated cultures). However, a simultaneous decrease in the numbers of myeloid progenitor cells (CFU) was observed. Interestingly, there was a selective stimulation of the growth of leukemic progenitors (AML-CFU). Indeed, whereas on day 0 these cells were detected in only 2 patients, between weeks 1 and 5 they were detected in 10 of the 14 patients included in the study. It is noteworthy that around 50% of the cells detected in the non-adherent fraction of rhGM-CSF-treated AML LTMC were blasts, whereas in untreated cultures, blasts corresponded to only 23% of the non-adherent cells, and the majority corresponded to cells of the monocyte-macrophage lineage. These results indicate that rhGM-CSF is a cytokine with a significant stimulatory activity for the in vitro growth of AML progenitor andblast cells, and, together with previous reports in the literature, suggest that the use of rhGM-CSF in clinical settings must be taken with caution since this cytokine, although beneficial in reducing the risk of infections after chemotherapy, may induce the reappearance of the disease after treatment. Further studies should be encouraged to understand in greater detail the effects of rhGM-CSF, and other cytokines, on the hematopoietic system of AML patients.

Incidence of aplastic anemia in a defined subpopulation from Mexico City.

Aplastic anemia (AA) is a hematological disease characterized by the deficient production of blood cells. The incidence of AA worldwide is low (1-5 new cases per 10(6) individuals per year). In contrast to other countries, no current reports exist on the incidence of this disorder in Mexico. In the present study, we have determined the incidence of AA in a defined subpopulation from Mexico City during the period 1996-2000. For the purpose of this study, we focused on the experience from a single medical institution: the Mexican Institute of Social Security (IMSS), which covers around 50% of Mexico's population. The incidence of AA was determined based on the actual number of patients diagnosed with this disease at the IMSS in Mexico City in a given year and the total number of individuals registered at the IMSS in Mexico City in the same year. Considering the IMSS population as a whole, the annual incidence of AA was 3.9 new cases per 10(6) individuals per year. In the pediatric population, the annual incidence was 4.2 new cases per 10(6) individuals per year, whereas in people 15-years-old and older the incidence was 3.8 new cases per 10(6) individuals per year. These incidences were higher than those reported in most studies from the USA, Europe and Israel. Compared to the incidence in Thailand, the incidence we observed in children was considerably higher, whereas the one in adults was similar to the one in that country. The results of the present study suggest that the incidence of AA in Mexico City is one of the highest worldwide, particularly in terms of the pediatric population; however, these results must be taken with caution since this study comprises only a subpopulation from Mexico City and not the entire population. Thus, further studies including a broader population, both in Mexico City and other urban and rural areas of this country, will be necessary in order to obtain better and more complete estimates of the actual incidence of AA in Mexico.

Sequential Variations in the Content of Bone Marrow Colony-forming Cells in Individual Patients with Aplastic Anemia Before and After Immunosuppressive Therapy; Hematopoiesis.

Previous studies have shown that the levels of hematopoietic progenitor cells (colony-forming cells; CFC) are drastically reduced in the vast majority of patients with aplastic anemia (AA). This has been observed both in patients before and after immunosuppressive therapy. In those studies, however, both groups of patients were usually formed by different individuals, thus it was not possible to follow the kinetics of such cells in each particular patient. In the present study, we have determined the content of myeloid and erythroid CFC in individual AA patients before and after therapy. Treated patients were studied at two different times (8-18 months apart) to detect any possible variations due to the ongoing treatment. At diagnosis, the levels of both myeloid and erythroid CFC were drastically reduced, as compared to normal bone marrow, in all the patients studied. This correlated with very low levels of leukocytes and hemoglobin in circulation. After the patients entered an immunosuppressive treatment, all of them showed significant increments in their CFC levels, and this correlated with increments in their hematological parameters in peripheral blood. However, in most patients CFC levels were still below the normal range. When the second sample after treatment was obtained, great variations in CFC numbers were observed. In terms of erythroid CFC levels, a further increase was seen in most patients, and this correlated with a further increase in hemoglobin levels. In contrasts, the levels of myeloid CFC were increased in only some of the patients, whereas in others, significant reductions were evident. Interestingly, in this latter group of patients, CFC never reached the levels observed before treatment. Our results indicate that, in a significant proportion of patients, a common pattern seems to exist. That is to say, low CFC numbers are present before treatment; an increase in the numbers of such cells results as an effect of the immunosuppressive therapy and further variations in CFC numbers (within individual limits that may differ significantly from one patient to another) take place as long as the treatment continues. Finally, we observed a correlation between CFC levels and the clinical status of the patients, i.e., those patients that showed a complete or a partial response to treatment showed higher levels of both myeloid and erythroid CFC than those patients that did not respond to therapy.

Niveles séricos de eritropoyetina en sujetos sanos estudiados en el valle de México / Erythropoietin seric levels in healthy student subjects in the Valley of Mexico

La eritropoyetina (EPO) es el factor humoral directamente resposable de la eritropoyesis, y su secreción se relaciona con el grado de oxigenación tisular. En altitudes por arriba del nivel del mar; las concentraciones de oxígeno son menores, lo que podría influir en los niveles séricos de EPO y de esta manera explicar el aumento de las cifras de hemoglobina y hematócrito. Por otro lado, la determinación de sus niveles sanguíneos es de gran importancia tanto en el diagnóstico diferencial de las anemias, como en el estudio de la eritrocitosis, en especial la policitemia rubra vera, enfermedad en que sus niveles son normales o bajos. Por tal motivo estimamos conveniente determinar las cifras que podrían ser consideradas como valores de referencia en población residente en la ciudad de México. Se estudió un total de 220 sujetos sanos, 168 hombres y 52 mujeres. Los niveles de EPO sérica, determinados por radioinmunoanálisis resultaron, en todo el grupo, con una mediana (Md) de 7.5 mU/ml, con un intervalo percentilar, (IP) de 1 a 18; en el sexo masculino la Md fue de 7.6 con un IP de 1 al 18 y en el sexo femenino Md de 7.5 con un IP de 1 a 16.9

Cinco episodios de anemia aplástica transitoria en tres enfermos / Five episodes of transiet aplastic anemia in three patients

Se informan cinco episodios de anemia aplástica (AA) grave en tres enfermos, dos mujeres y un varón, de 32, 56 y 41 años de edad, respectivamente, el último con tres episodios. Fueron relacionados con exposición a insecticidas, solventes y fármacos (trimetoprim con sulfametoxazol, pirimetamina y derivados de pirazolanas). Acudieron con padecimintos de dos semanas de evolución con anemia, púrpura mucocutánea y en tres episodios fiebre. Como tratamiento en tres casos se utilizó prednisona y danazol por 10 días, así como antibióticos. En todos los casos se observó recuperación espontánea al cabo de 16 a 45 días que no se correlacionó con infección viral, hemoglobinopatía o evidencia de proceso mieloproliferativo. Se diagnósticaron como AA transitoria, variante de la AA con recuperación temprana y completa de la hematopoyesis

Treatment results of 23 cases of severe aplastic anemia with lymphocytapheresis

We report the results of 23 patients with aplastic anemia (AA) treated with a program of 14 lymphocytapheresis (LC). Treatments were performed with apheresis machines, models Haemonetics 30-S and Baxter CS3000, using the standard program. This procedure was done because AA in many cases appears as a result of the action of a T cell population that inhibits hematopoiesis. Theorically, removal of this clonal population would produce hematopoietic recovery. Of the total of 23 patients, 9 were excluded for final evaluation of treatment results because 7 died during or shortly after treatment (0.7-3 months); one patient abandoned treatment after three LC and another died 7 months later because of transformation to acute leukemia. The ramaining 14 patients were included in the final evaluation of treatment; seven females and seven males, average age 46.1 years (range 22-69); 13 with severe, and one with moderate AA; 11 with recently diagnosed, and 3 with chronica AA; 12 without previous treatment and two treated before with antilymphocyte globulin + oxymetholone (OXN) + cyclosporine A (CsA) with transiet partial remission (PR). Besides lymphocytapheresis, 13 patients received OXM; 4 of them GM-CSF ad one low dose CsA. Four patients had complete remission lasting >59.5 months (range 42-78); eight PR (average duration of >38.6 months), and two minimal remission (>37 and 29 months). Platelet, reticulocyte and granulocyte counts increased on average at 48.7, 73.3 and 91.4 days, respectively. In cocnlusion, 14 (60.8 perecent) of 23 patients with AA showed an improvement related to LC treatment, with a survival probability of 63 percent from the fourth month, the latter with and added beneficial effect of the other therapies used. Larger numbers of patients have to be treated with LC to determine its real usefulness, mechanism of action and the best conditions for its use

Tratamiento de la hemoglobinuria paroxística nocturna con globulina antilinfocitaria / Antilymphocyte globulin therapy for paroxysmal nocturnal hemoglobinuria

Objetivo. Evaluar la utilidad de la globulina antilinfocitos T humanos (GAL) en el tratamiento de la hemoglobinuria paroxística nocturna (HPN). Diseño. Estudio prospectivo, no controlado de casos clínicos. Ubicación. Servicio de Hematología, Hospital de Especialidades Centro Médico Nacional Siglo XXI, IMSS, México. Pacientes. Se incluyeron seis pacientes, tres varones y tres mujeres con edad promedio de 37.5 años. El diagnóstico de HPN se estableció por datos clínicos y pruebas de Ham, sucrosa e inulina positivas. Se consideró grave en cuatro enfermos en virtud de su actividad hemolítica continua e intensa, y los requerimientos transfusionales altos (más de dos concentrados de hematíes por mes); cinco de ellos no habían tenido mejoría con esteroides y/o andrógenos; uno no tenía tratamiento previo. Intervención. Se aplicó GAL (Lymphoglobuline Mérieux, Lyon, Francia; lote E 0034) 10 mg/kg/día por cuatro días, en infusión de 20 horas; también recibieron metilprednisolona, 500 mg/día, en infusión de dos horas cambiando, al cabo de siete días, a prednisona de 1 mg/kg y en dosis decrecientes hasta suspenderla en 30 días. Criterios de respuesta. Se valoró por medio del aumento en el nivel de homoglobina, la disminución o ausencia en los requerimientos transfusionales de glóbulos rojos, y la mejoría de la cuenta de plaquetas, granulocitos o ambas, en los tres meses posteriores al tratamiento con GAL. Resultados. En dos enfermos la primera dosis de GAL provocó una reacción anafiláctica y fueron excluidos del estudio. De los cuatro enfermos restantes, sólo dos mostraron respuesta a las 12 semanas post-tratamiento, uno total y otro mínima; ambas respuestas fueron transitorias. En un seguimiento promedio de 12.5 meses, ninguno de los pacientes mostraba mejoría. En los cuatro sujetos hubo necesidad de reiniciar tratamiento en danazol y prednisona. Conclusiones. El paciente con HPN en actividad intensa, la terapéutica con GAL, en las dosis y tiempo dados, no ofreció ningún beneficio. En consecuencia, se deben buscar otras alternativas para tratar a estos enfermos

Tratamiento de la hemorragia intracraneana en la púrpura trombocitopénica idopática crónica / Treatment of intracraneal hemorrhage in chronic idiopathic thrombocytopenic purpura

Se informan los casos clínicos de dos pacientes con púrpura trombocitopénica idiopática crónica (PTIC) y hemorragia petequial intracraneana en las que el tratamiento convencional de esta complicación fue ineficaz; en cambio, en coincidencia con la aplicación de la vincristina se observó desaparición inmediata de sus manifestaciones neurológicas y aumento de las plaquetas con recuperación clínica total. Esta evolución contrasta con la informada en enfermos similares tratados con corticosteroides o esplenectomía, entre los que la mortalidad en ocasiones llegó a ser de 100 por ciento. La reacción favorable fue atribuída al efecto de la vincristina. Llama la atención, sobre todo, la mejoría inmediata de las manifestaciones neurológicas. Se propone su utilización en cojunto con las medidas tradicionalmente empleadas en el control de esta grave complicación, en particular en pacientes con complicaciones para la esplenectomía urgente.