RESUMEN
Vascular involvement is presently considered a "common pathway" in a number of diseases that is mediated by circulating immune complexes (CIC). CIC are found in the circulation when the disease is active and in single patients their level may parallel disease activity. Lepromatous leprosis is characterized by the presence of CIC and deposits of immunoglobulins and complement in vascular lesions of the different organs and an Arthus-like mechanism is considered as the basis for the clinical picture. The same mechanism is considered to play an essential pathophysiologic role in Lucio's phenomenon, which is characterized by lymphohistiocytic vascular infiltrates with or without thrombosis and secondary cutaneous infarction. Lepromatous vascular involvement is mediated by CIC whose antigen composition is known, the same as it is with HCV mediated cryoglobulinemia, HBV positive panarteritis nodosa, rheumatoid vasculitis, or Wagner's granulomatosis, which are usually treated by PE [1-3]. PE has been employed for lepromatous vasculitis since 1979 [4] and other cases have been successfully treated afterwards [5,6]. We report on another patient successfully treated by plasma exchange.
Asunto(s)
Lepra Lepromatosa/complicaciones , Lepra Lepromatosa/terapia , Intercambio Plasmático , Vasculitis/etiología , Vasculitis/terapia , Humanos , Lepra Lepromatosa/inmunología , Persona de Mediana Edad , Vasculitis/inmunologíaRESUMEN
Since 1989 we have been collecting dry-platelets on a routine basis. Dry-platelets are those collected along with 25-30 ml of contaminating plasma cell with separators such as the Amicus, AS 104 and the Excel Pro. Platelets are resuspended in non plasma media for storage and for at least 60 hours their viability and functionality are not impaired. In this article we report on two hemolytic crises determined by two O Rh D + units of single donor platelets (SPD) taken from the same donor in a double-apheresis session. The two split units were administered to two A Rh D + patients suffering from metastatic breast cancer and severe aplastic anemia (SAA) respectively. In both cases the hemolytic reaction was of the intravascular type, with a drop in hemoglobin (Hgb) level from 8.6 to 5.4 and from 8.8 down to 5.3 g/dl respectively. From the patients' RBC only alpha agglutinins were eluted and donor's indirect antiglobulin test (IAT) was negative with extended panel RBCs. In the first case the clinical course after erythroexchange (Erex) was uneventful whereas in the second one, that suffering from SAA, after Erex, acute renal failure and shock did complicate the clinical course and the patient died seven days after the incriminated platelet transfusion.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Hemólisis , Transfusión de Plaquetas/efectos adversos , Adolescente , Adulto , Anemia Aplásica/terapia , Neoplasias de la Mama/terapia , Femenino , HumanosRESUMEN
TTP remains enigmatic both in terms of etiology and management. The most recent approach is aggressive plasma exchange (PE) employing cryopoor plasma for replacement, based on the pathogenetic relevance given to exceedingly large Von Willebrand (VWF) multimers in the determination of the syndrome with normalization during remission. PE with fresh frozen plasma (FFP) is better than FFP infusion as shown by a recent Canadian study, supporting the theory that to treat TTP an offending circulating agent needs to be removed from the patient's plasma in contrast to the hypothesis that a missing factor is to be given along with FFP. A more recent hypothesis is supported by the results of studies published by the end of 1998 [Moake J, Chintagumpala M, Turner N et al. Blood 1994;84:490-97; Moake J, McPherson PD. Am J Med 1989;87: 3-9N] which would show that TTP is mediated by auto-antibodies to VWF-cleaving protease, or is the result of deficiency of the protease ascribed to abnormalities in its production, function or survival. Plasmapheresis without plasma infusion is relatively ineffective perhaps because it does not increase the protease activity. Cascade filtration (CF) is the autologous counterpart of plasmapheresis. It has been used by our group since 1980 to remove from patients plasma macromolecules such as VWF, fibrinogen, LDL and circulatory immune complexes (CIC). After secondary filtration, the autologous plasma has a composition which is very similar to that of allogeneic plasma after cryoprecipitation, a product which used in the management of TTP. Based on this knowledge, in 1994 we began to use CF in the treatment of TTP patients. In the beginning (7 patients) CF was combined with a decreasing number of conventional PEs using allogeneic plasma for substitution. Lately only CF with some plasma supplementation has been used in the last 9 cases. From a clinical point of view our 16 patients achieved remission after a number of treatments (11 +/- 7) that compares sufficiently well with those required by our historical control group of 47 cases (14 +/- 13). Of course the patient's exposure to allogenic plasma was significantly lower for patients in the CF only group (1.4 +/- 1.2 plasma U/session) compared to the PE + CF group (4.4 +/- 2.3 plasma U/session) or for the controls treated by PE only (10.8 +/- 4.6 plasma U/session). There were no deaths in the CF or PE + CF groups and no untoward effect was observed. On the contrary there were 5 deaths (1 on the day of presentation) in the PE group, and 1 HBV and 2 HCV infections as well as 4 severe allergic reactions to plasma proteins (or passive antibody infusion). We conclude that CF is presently the best treatment to offer to patients suffering from sporadic TTP and that CF may contribute to expanding the knowledge of the pathogenetic mechanisms of this uncommon multisystem disorder.
Asunto(s)
Hemofiltración/normas , Intercambio Plasmático/normas , Púrpura Trombocitopénica Trombótica/terapia , Adulto , Antineoplásicos Fitogénicos/uso terapéutico , Aspirina/uso terapéutico , Eliminación de Componentes Sanguíneos , Dipiridamol/uso terapéutico , Femenino , Hemofiltración/métodos , Humanos , Masculino , Persona de Mediana Edad , Intercambio Plasmático/métodos , Vincristina/uso terapéuticoRESUMEN
In apheresis, leukodepletion by secondary filtration of the platelet components or by the primary use of special high efficiency apparatuses is widely used to meet current clinical practice. Leukodepletion of RBC is mandatory for hematooncological patients and new filters for plasma are progressively being introduced in the routine of European blood banks. However, since the monitoring of leukodepletion efficiency continues to be carried out manually using the Nageotte or the microdroplet fluorescence assay (MFA), inaccuracy and labour-intensity of counting will limit the possibility of satisfying the increasing demand for leukodepletion monitoring. Volumetric capillary cytometry (VCC) is a totally automated system that has been shown to correlate well with Nageotte, MFA and flow-cytometric countings of residual leukocytes in platelet and RBC product. In this article we describe the application of VCC in the quality control program of our hemapheresis unit in which all apheresis donations are of the multicomponent collection type.
Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Citometría de Flujo , Automatización , Eliminación de Componentes Sanguíneos/instrumentación , Filtración , Citometría de Flujo/instrumentación , Citometría de Flujo/métodos , Humanos , Recuento de Leucocitos , Recuento de PlaquetasRESUMEN
Transfusion of predeposit or salvaged autologous blood has continued to grow since the 1980s. Issues such as the indications for use and cost effectiveness as well as the safety of autologous blood salvaged during cancer surgery have emerged and should be addressed. The concern for possible contamination of autologous RBC with cancer cells responsible for metastasis has limited the use of autologous salvaged blood in cancer patients. Nevertheless, clinical experience has been gained on the use of salvaged blood in patients with colorectal, gastric, renal, hepatic, breast, bladder and lung cancer. No evidence has been reported showing an increase in metastasis or a decrease in patient survival, in spite of the obvious demonstration that salvaged blood is contaminated with viable tumor cells which are not washed out of the RBC layer during intraoperative blood salvage (IOBS). However, a number of limitations have hampered the widespread use of IOBS in these patients and the technique is not well established. Increasing knowledge of the deleterious effects of allogeneic blood transfusion both in terms of the increased number of viral or bacterial infections and the down-regulation of the patient's immune system have recalled attention to IOBS and to the techniques such as filtration, which might reduce the risk of reinfusion of cancer cells, or totally eliminate the risks such as irradiation has been proposed by Hansen's group. This paper reviews the topic with some emphasis on our personal experience with gamma and X-ray irradiation of salvaged blood in a large reference hospital, where IOBS and filtration of salvaged blood were established for use in cancer patients in 1993 and 1996.
Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Transfusión de Sangre Autóloga/métodos , Cuidados Intraoperatorios/métodos , Neoplasias/cirugía , Sangre/efectos de la radiación , Transfusión de Sangre Autóloga/efectos adversos , Radioisótopos de Cesio , Procedimientos Quirúrgicos Electivos , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Neoplasias/sangre , Células Neoplásicas Circulantes/efectos de la radiación , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: The main objective of this pilot study was to assess the possibility of achieving engraftment of HLA-matched sibling donor mobilized hematopoietic stem cells after immunosuppressive non-myeloablative therapy. The second objective was to verify whether high-dose therapy with autologous stem cells rescue followed by allografting conditioned by only an immunosuppressive regimen, can be combined in order to achieve the reduction of tumor burden after autografting and the control of residual disease with immune-mediated effects after allografting. DESIGN AND METHODS: To enter the pilot study the patients had to fulfil the following criteria: advanced resistant disease, presence of an HLA matched sibling donor, no general contraindications to stem cell transplantation. Our data refers to 9 patients: Hodgkin's disease (n = 4), non-Hodgkin's lymphoma (n = 2), advanced chronic myelogenous leukemia (n = 2) (one patient with accelerated phase Ph-negative but p190 BCR-ABL gene positive by RT-PCR and one with Ph-positive blastic phase), refractory anemia with excess of blasts t(1;3) (p36;q21) (n = 1). All patients but one received the combined approach. At a median of 40 days (range 30-96), after high-dose therapy and autologous stem cell engraftment, the patients were treated with immunosuppressive therapy consisting of fludarabine and cyclophosphamide (Flu-Cy protocol) and then HLA matched donor mobilized stem cells were infused into the patients. GvHD prophylaxis consisted of cyclosporin and methotrexate. RESULTS: To date, with a median observation period of 4 months (range, 2-10), complete chimerism (100% donor cells) has been achieved in 6 patients. Three patients did not achieve complete chimerism: one patient died of progressive Hodgkin's disease when he reached 55% of donor cells, another patient is now in increasing phase of donor cell engraftment and the last patient (blastic phase-CML) was the only case who appears to have had autologous recovery. Two of the Hodgkin's disease patients, who were in partial remission after autografting, achieved complete remission after allografting and both are disease free 2 and 6 months after. Another Hodgkin's disease patient is alive at 10 months but she has progressive disease. One of the two patients with non-Hodgkin's lymphoma, who achieved partial remission after autografting, obtained complete remission and he is disease free 2 months after allografting. The other patient maintains partial remission obtained after autografting. The accelerated phase-CML patient obtained hematologic and molecular remission; the RAEB patient achieved hematologic and cytogenetic remission. In two patients severe aGVHD (grade II-III) was the single major complication but neither patient died of it. Mild aGVHD was seen in another patient. In only one patient did the ANC decrease to below 1 x 10(9)/L and in no case did platelets decrease below 20 x 10(9)/L. No patients required a sterile room or any red cell or platelet transfusions. INTERPRETATION AND CONCLUSIONS: Immunosuppressive therapy with a Flu-Cy protocol allowed engraftment of HLA-matched sibling donor stem cells without procedure-related deaths; moreover, we have demonstrated that this combined procedure can be pursued in safety in a serious ill population and some of these patients achieved a complete remission. This procedure is not likely to be curative, but a fascinating step along the path to curing these diseases. Of course, the follow-up is too short to document the incidence of cGvHD.
Asunto(s)
Supervivencia de Injerto , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Adulto , Femenino , Rechazo de Injerto/prevención & control , Neoplasias Hematológicas/patología , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana EdadRESUMEN
This trial was designed to test the use of CD34+ selected haemopoietic stem cells (HSC) in HLA-mismatched donor-recipient pairs, following intensive conditioning with thiotepa, antilymphocyte globulin (ALG), cyclophosphamide and single-dose total-body irradiation (sTBI). 10 patients aged 16-50 with advanced malignancies and a two- or three-antigen mismatched family donor entered this study. Donor marrow and G-CSF primed peripheral blood cells were processed separately on CD34 columns (Ceprate). The median number of infused CD34+ cells were 5.66 x 10(6)/ kg, with 0.55 x 10(6)/kg CD3+ cells. Nine patients received cyclosporin for graft-versus-host disease (GvHD) prophylaxis. Median neutrophil counts on day 21 were 2 x 10(9)/l with a median platelet count of 60 x 10(9)/l, but CD4 counts remained extremely depressed throughout the study. Acute GvHD was scored as grade 0-I in two patients, as grade II in seven, and grade III in one. Eight patients died at a median interval of 72 d from HSCT (range 20-144) due to cytomegalovirus (CMV) associated interstitial pneumonitis (IP) (n = 5), renal failure (n = 1). GvHD (n = 1) and Aspergillus meningitis (n = 1). Two patients are alive 365-495 d post transplant, one in remission and one in relapse. This study suggests that large numbers of positively selected mismatched HSC can rapidly engraft after intensive conditioning regimen: however, profound post-transplant immunodeficiency leads to a high risk of lethal infectious complications.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndromes de Inmunodeficiencia/etiología , Linfoma no Hodgkin/terapia , Trastornos Mieloproliferativos/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Antígenos CD34 , Trasplante de Médula Ósea/métodos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Causas de Muerte , Infecciones por Citomegalovirus/etiología , Supervivencia de Injerto , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Acondicionamiento Pretrasplante/métodos , Trasplante HomólogoRESUMEN
The Amicus cell separator is the latest apparatus introduced into the international market for high-yield, low WBC contamination and short-procedure time thrombocytapheresis. In its original configuration the apparatus collects platelets for subsequent resuspension in plasma and no collection of PRBC can be carried out along with thrombocytapheresis. In this paper we present the results of plasma-thrombocytapheresis and erythro-thrombocytapheresis after the adaptation of the Amicus to the collection and storage of platelets in a non-plasma medium and the concurrent collection of PRBC. From our study it is concluded that PRBC collection doesn't modify the quality of the platelet product obtained from random donors (platelets pre-count 263x10e3/microliter) in terms of yield which is 4.6x10e11 platelets, WBC contamination (1.3x10e5) or procedure time (63 +/- 26 min.). The quality of the platelet products is satisfactory too, as measured by aggregation induced by collagen and ristocetin or by the substantial stability of membrane glycoproteins (CD62-63-51-36-42B). The concentrate had an average content of 58.8 g of hemoglobin per bag, a final volume of 376 +/- 13 ml, (after the addition of 100 ml of SAG-M) and a normal mechanic and osmotic fragility.
Asunto(s)
Conservación de la Sangre , Plaquetoferesis/instrumentación , Eliminación de Componentes Sanguíneos/instrumentación , Eritrocitos , Femenino , Humanos , Masculino , Plasmaféresis/instrumentación , Agregación Plaquetaria , Glicoproteínas de Membrana Plaquetaria/análisisAsunto(s)
Plaquetas/citología , Separación Celular/métodos , Transfusión de Plaquetas , Humanos , ItaliaRESUMEN
Thirty-one patients (median age, 44 years) with advanced hematologic malignancies were given thiotepa 15 mg/kg, and cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one antigen mismatched family donor (n = 3). Donors were mobilized with granulocyte colony-stimulating factor 5 to 10 microgram/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients body weight was as follows: nucleated cells 13 x 10(8)/kg; CD34+ cells 6 x 10(6)/kg; colony-forming unit-granulocyte macrophage 38 x 10(4)/kg, and CD3+ cells 449 x 10(6)/kg. The diagnoses were chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or lymphoid leukemia (n = 2), acute myelofibrosis (n = 2), multiple myeloma (n = 1), lymphoma (n = 6), chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 10(9)/L and platelet counts of 30 x 10(9)/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or DNA polymorphism in 29 of 31 patients: one had early leukemia relapse and one patient was unevaluable because of early death. Acute graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were leukemia (n = 4), acute GVHD (n = 4, with associated cytomegalovirus infections in three), sepsis (n = 1), liver failure (n = 1), multiorgan failure (n = 1), and hemorrhage (n = 1). The actuarial transplant mortality is 29%, the actuarial relapse rate 22%. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57%. Three patients received PBSCT from family donors mismatched for one class II antigen: all engrafted, one developed grade I aGVHD; one died of leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced leukemia, also in the setting of one antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades de la Médula Ósea/prevención & control , Médula Ósea/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/farmacología , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/efectos de los fármacos , Leucemia/tratamiento farmacológico , Análisis Actuarial , Adulto , Anciano , Enfermedades de la Médula Ósea/inducido químicamente , Trasplante de Médula Ósea , Recuento de Linfocito CD4 , Causas de Muerte , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/farmacología , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Infecciones/etiología , Infecciones/mortalidad , Leucaféresis/efectos adversos , Leucemia/sangre , Leucemia/mortalidad , Leucemia/terapia , Linfoma/sangre , Linfoma/tratamiento farmacológico , Linfoma/terapia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/terapia , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/mortalidad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/terapia , Proyectos Piloto , Mielofibrosis Primaria/sangre , Mielofibrosis Primaria/tratamiento farmacológico , Mielofibrosis Primaria/terapia , Terapia Recuperativa , Análisis de Supervivencia , Tasa de Supervivencia , Tiotepa/administración & dosificación , Donantes de Tejidos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
A new CFC apparatus for intraoperative blood salvage (CATS) has been introduced by Fresenius and submitted to preliminary evaluation at our hemapheresis unit. The volume of shed blood submitted to washing was 1714 +/- 496 with a hematocrit of 19% and the volume of PRBC ready for transfusion 297.9 ml with hematocrit of 64.3%. Elimination of contaminant activated platelets and WBC was 92% and 74% respectively. Elimination of contaminants such as protein, free hemoglobin, LDH and K ions was always over 95%. Regular application of CATS is warrented after our study.
Asunto(s)
Transfusión de Sangre Autóloga , Eritrocitos/citología , Leucocitos/citología , Tamaño de la Célula/fisiología , Hematócrito , Humanos , Complicaciones Intraoperatorias , Activación Plaquetaria , Estudios RetrospectivosRESUMEN
The number of conditions that can benefit from Plasma-Exchange (PE) continues to grow. We have recently added to the list the Cyclosporin-A induced hypertrygliceridemia and myoglobinuric acute renal insufficiency. Such as any therapeutic measure for PE, four evolutive phases can be recognized: the discovery and research, the confirmation of indications, the routine applications and the decline, when new more powerful tools are offered by culture or technology. We have participated in the first three phases during the last 20 years. Not necessarily all experiences were favourable. Nonetheless, we feel that, for the time being, a hemapheresis unit is an absolute necessity for a medium - sized hospital even if only therapeutic procedures are carried out. The phase four, decline of interest and applications, cannot be foreseen. Finally the ability of PE to shorten substantially the length of hospital stays along with the ease with which procedure can be performed on ambulatory patients, substantiate a favourable cost/benefit ratio for this therapeutic modality.
Asunto(s)
Intercambio Plasmático , Plasmaféresis , Humanos , Intercambio Plasmático/efectos adversos , Plasmaféresis/efectos adversosRESUMEN
The aim of this study was to test whether prolonged administration of granulocyte colony-stimulating factor (G-CSF) would allow the collection by leukapheresis of PBHP in patients with SAA. For this purpose, nine SAA patients, 7 to 46 years old, six of whom were enrolled at diagnosis of their disease and three after previous immunosuppression had failed, were treated with antilymphocyte globulin (ALG) (day 1 to 5), cyclosporin A (5 mg/kg/d orally) (day 6 to 90) and G-CSF 5 micrograms/kg/d (day 6 to 90). A total of 40 leukaphereses were performed, (range 2 to 7 per patient), between days +10 and +168 from G-CSF treatment. White blood cell count at the time of harvest ranged from 1.2 to 18.1 x 10(9)/L. Results can be summarized as follows: the median number of cells collected per patient was 5.0 x 10(8)/kg (range 2.6 to 18.7), the median number of CD34+ cells was 1.8 x 10(6)/kg (range 0.27 to 3.8) and the median number of colony-forming units granulocyte-macrophage (CFU-GM) was 3.9 x 10(4)/kg (range 0 to 39). Twenty leukaphereses performed between days +33 and +77 of G-CSF treatment grew granulocyte macrophages and erythroid colonies in vitro. No colony growth was obtained from 20 leukaphereses performed before day +33 or after day +80. In six patients the total number of CFU-GM recovered were in the range described for autologous peripheral blood stem cell grafts. (2.6 to 39 x 10(4)/kg). In conclusion, this study suggests that circulating hematopoietic progenitors can be recovered after ALG priming and after at least 1 month of G-CSF treatment in a proportion of patients with SAA. Whether these cells will be suitable for autologous transplantation remains to be determined.
Asunto(s)
Anemia Aplásica/sangre , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Células Madre Hematopoyéticas/citología , Adolescente , Adulto , Anemia Aplásica/tratamiento farmacológico , Antígenos CD/análisis , Antígenos de Superficie/análisis , Antígenos de Superficie/genética , Suero Antilinfocítico/uso terapéutico , Niño , Preescolar , Ciclosporina/uso terapéutico , Femenino , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Depleción Linfocítica , Masculino , Persona de Mediana Edad , Fenotipo , Linfocitos T/citología , Factores de TiempoRESUMEN
Forty patients with Ph-positive blastic phase (BP) (28 patients) or chronic phase (CP)-CML (3 patients) and relapsed adult acute lymphoblastic leukemia (ALL) (9 patients) with cytogenetical translocations [t(8;14):2 patients; t(4;8):2 patients; t(4;11):3 patients; t(9;22):2 patients], received an intensive conventional chemotherapy. During early recovery from marrow aplasia, when WBC reached 0.3-1.5 x 10--9/L, peripheral blood stem cells (BSC) were collected by 4-8 leukapheresis consecutively. BSC collected from the 2/3 patients with CP-CML resulted Ph-negative and PCR negative. In 8 out of 26 BP-CML patients, BSC resulted Ph-negative and in two cases PCR negative. Of the nine ALL patients, 6 patients lost the cytogenetic translocations, one patient died during aplasia, two patients did not have cytogenetic modifications and died in few weeks of leukemia and one patient out of six responding patients relapsed before transplant. After complete recovery, 15 patients (BP-CML:8 patients; CP-CML:2 patients; ALL:5 patients) were subsequently given high-dose therapy (VP-16 +/- Cy+TBI in single dose) followed by reinfusion of "normal" BSC. Both the patients in CP-CML and 5/5 patients with ALL maintain clinical and cytogenetic remission; all the patients transplanted in BP-CML relapsed 5-18 months post-transplant. It is concluded that intensive conventional chemotherapy employed in CML and ALL can lead to a precocious overshoot of cytogenetically normal BSC.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Células Madre Hematopoyéticas/ultraestructura , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Translocación GenéticaRESUMEN
Malaria has become a very uncommon disease in Italy. Recently a variety of circumstances, such as travel to tropical countries as well as immigration from Asia and Africa, have combined to increase the number of malaria cases recorded annually. In this report we describe the use of red cell exchange transfusion and plasma exchange in the treatment of a patient with hyperparasitemic malaria (51% erythrocytes or more parasitized). When first observed the patient was in shock and had signs of cerebral malaria, disseminated intravascular coagulation, and acute respiratory distress syndrome, which in the following 2 days were complicated by acute renal failure. After mefloquine therapy combined with 3 red blood cell exchanges, 2 plasma exchanges, and 10 dialysis sessions over 14 days, the patient recovered completely. This case of severe malaria with multiple complications, treated with mefloquine in conjunction with both exchange transfusion and plasmapheresis, had a successful outcome and lends further support to the possible beneficial role of exchange transfusion in complicated malaria.
Asunto(s)
Lesión Renal Aguda/etiología , Eliminación de Componentes Sanguíneos , Coagulación Intravascular Diseminada/etiología , Malaria Cerebral/etiología , Malaria/terapia , Síndrome de Dificultad Respiratoria/etiología , Enfermedad Aguda , Anemia/etiología , Transfusión de Componentes Sanguíneos , Humanos , Hiperbilirrubinemia/etiología , Malaria/complicaciones , Masculino , Persona de Mediana Edad , Intercambio PlasmáticoRESUMEN
The expansion of the Philadelphia (Ph) chromosome positive clone in chronic myeloid leukemia (CML) may depend on its capacity to suppress the proliferation of Ph-negative stem cells, but this proliferative advantage might, in certain circumstances, be reversible. Various lines of evidence suggest that Ph-negative cells, albeit in a suppressed state, must still be present. As recently suggested, the expansion of 'putative' normal Ph-negative hemopoietic stem cells might have, in certain circumstances, a proliferative advantage over the Ph clone in CML. This suggests that the treatment of CML with intensive chemotherapy might allow the collection of Ph-negative hemopoietic cells in the early phase of recovery. Eight patients with acute phase chronic myelogenous leukemia (AP-CML) were treated with idarubicin, intermediate dose cytarabine and etoposide. During recovery from bone marrow aplasia, when the white blood cell count reached 0.3-1 x 10(-9), blood cells were collected with 2-5 (median 3) consecutive leukapheresis. In 5/8 patients, these peripheral cells were Ph-negative at the cytogenetic analysis. Moreover, in one case the polymerase chain reaction analysis performed to detect the presence of minimal residual disease in the cells collected by leukapheresis was negative, further confirming that this approach may induce a very high degree of suppression of the Ph-positive clones. After complete recovery, these five patients were subsequently treated with high-dose etoposide, cyclophosphamide and total body radiation (10 Gy, single dose) followed by reinfusion of Ph-negative peripheral blood stem cells. All these patients received cyclosporine A post-autotransplant in an attempt to induce acute graft-versus-host-disease. Three of 5 patients remain in clinical and cytogenetic remission 5-15 months post-transplant. It is concluded that Ph-negative peripheral blood stem cells can be recovered from patients with AP-CML and used successfully to restore Ph-negative hemopoiesis after high dose therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Células Sanguíneas/trasplante , Ciclosporinas/uso terapéutico , Leucemia Mieloide de Fase Acelerada/terapia , Adulto , Anciano , Terapia Combinada , Citarabina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Idarrubicina/administración & dosificación , Leucemia Mieloide de Fase Acelerada/tratamiento farmacológico , Leucemia Mieloide de Fase Acelerada/genética , Masculino , Persona de Mediana Edad , Cromosoma Filadelfia , Trasplante AutólogoRESUMEN
If ABO antigens/antibodies play any role in the pathogenesis of acute graft-versus-host disease (GVHD), one would expect the highest incidence of GVHD in recipients of minor ABO-mismatched grafts, followed by ABO-matched grafts, and the lowest incidence in major ABO-mismatched transplants. To test this hypothesis 174 patients receiving an HLA-identical allogeneic bone marrow transplant (BMT) for aplastic anemia (n = 32) or leukemia (n = 142) were analyzed for factors associated with acute GVHD. Variables analyzed included diagnosis, sex, age, blood group of donor and recipient, ABO compatibility, Rhesus compatibility, sex compatibility, number of bone marrow cells given at BMT, year of transplant, day of engraftment, and GVHD prophylaxis. We first carried out an exploratory contingency table analysis: minor ABO incompatibility was associated with a significantly higher risk of severe acute GVHD when compared with ABO-matched and major-ABO mismatched pairs (P = 0.003): 14/9, 57/67, and 5/22 patients developed, respectively, 0-I/II-IV acute GVHD in ABO major-mismatched, matched, and minor-mismatched pairs. Donors of group 0, (P = 0.06), older recipient's age (P = 0.08), fast engraftment (P = 0.03), and older donor's age (0.08) were also associated with a higher risk of GVHD. Recipient's ABO group, diagnosis, year of transplant, Rhesus group of donor or recipient, Rhesus compatibility, sex of donor or recipient, sex compatibility, and type of GVHD prophylaxis were not predictive of GVHD. A Cox multifactorial proportional hazards analysis confirmed that ABO matching was the single most significant factor associated with GVHD (P = 0.006). The cumulative incidence of GVHD grade II+ was 39%, 54%, and 82% for ABO major-mismatched, matched, and minor-mismatched pairs (P = 0.01). This study suggests that ABO antigens may play a role in the development of acute GVHD.