losartan-potassium and Graft-vs-Host-Disease

Topics: Animals; Aspirin; Cell Differentiation; Cell- and Tissue-Based Therapy; Erythropoietin; Graft vs Host Disease; Hematopoiesis; Hematopoietic Stem Cells; Humans; Leukemia; Mesenchymal Stem Cells; Mice; Neoplastic Stem Cells

Topics: Anemia, Hypochromic; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Small Cell; Clinical Protocols; Darbepoetin alfa; Data Interpretation, Statistical; Erythropoietin; Female; Filgrastim; Follow-Up Studies; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematinics; Hematologic Neoplasms; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Lung Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Male; Multicenter Studies as Topic; Neoplasms; Neutropenia; Platelet Aggregation Inhibitors; Polycythemia Vera; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Survival Analysis; Thrombocythemia, Essential; Treatment Outcome

Bone marrow suppression after intensive chemotherapies in patients with myeloid leukemia is severe, resulting in the reduction of the number of white blood cells, red blood cells, and platelets. Supportive therapies are indispensable for the management of these leukemia patients. The improvement of blood cell transfusion can decrease side effects of chemotherapies and establish the safety. But we still have notable side effects of transfusion such as TRALI (transfusion-related acute lung injury), platelet immunologic refractory state, and so on. Cytokine therapy especially with G-CSF (granulocyte colony-stimulating factor) administration, changed the treatment of myeloid leukemia. G-CSF can shorten the duration of neutropenia and decrease the risk of infection. Recently the effects of Epo (erythropoietin) on chemotherapy-induced anemia have been demonstrated. We discuss here the indications of blood cell transfusion and cytokine therapies in the treatment for myeloid leukemia.

Topics: Acute Lung Injury; Antineoplastic Agents; Blood Component Transfusion; Blood Transfusion; Erythropoietin; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid; Practice Guidelines as Topic; Transfusion Reaction

Topics: Adjuvants, Immunologic; Animals; beta-Glucans; Bone Marrow Transplantation; Clinical Trials as Topic; Cytokines; Erythropoietin; Glucans; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Humans; Interleukin-1; Interleukin-3; Macrophage Colony-Stimulating Factor; Oligopeptides; Pentoxifylline; Recombinant Proteins; Transplantation, Homologous

The use of the recombinant hematopoietic growth factors G-CSF and GM-CSF have shortened the period of neutropenia, or avoided this problem, in many cancer patients who have received cytotoxic therapy. Although these benefits have been particularly striking in the autologous bone marrow and/or autologous peripheral blood progenitor cell transplant setting, most data suggest that the use of G-CSF and GM-CSF only marginally enhance recovery of the neutrophil count when administered after allogeneic bone marrow infusion. Furthermore, in the allograft setting these expensive agents have not provided benefit in the form of enhanced platelet count recovery, lessening the incidence of graft-versus-host disease, or improvement in overall survival. These data do not justify routine widespread use of G-CSF and GM-CSF and suggest that these agents should be reserved for patients who experience delay in engraftment after allogeneic bone marrow infusion. Administration of erythropoietin, on the other hand, may reduce the need for homologous red blood cell transfusions, and may increase the safety margin for both the allogeneic bone marrow recipient and as well as the donor. Recombinant hematopoietic growth factors targetted specifically to enhance platelet recovery after transplantation (such as interleukin-3, interleukin-6, and interleukin-11) have shown promise after autotransplantation and after conventional dose chemotherapy, and likely will be evaluated in the allogeneic transplant patient.

Topics: Bone Marrow Transplantation; Clinical Trials as Topic; Erythropoietin; Graft Survival; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Humans; Lymphocyte Depletion; Macrophage Colony-Stimulating Factor; Neoplasms; Neutropenia; Recombinant Proteins; Transplantation, Homologous; Treatment Outcome

In the United States in 1991, 290,000 or 7.1% of the 4,110,907 live births were premature infants; 53,299 or 1.3% were infants with birth weights of less than 1500 grams. Many if not all of these very low birth weight infants will require red blood cell transfusions for one of several reasons. These include exchange transfusions for hyperbilirubinemia, but most often transfusions are simple small volume transfusion also called 'topper' transfusions. Most of these small volume transfusions are given for iatrogenic blood loss or 'bleeding into the laboratory.' Studies have demonstrated that the sicker the infant, the more blood sampling is needed and the greater the exposure to red blood cell (RBC), platelet and plasma products. Simple RBC transfusions may also be given for specific clinical indications or to maintain a predetermined hemoglobin concentration. This manuscript will review the criteria for RBC transfusion in neonates and selection of product as regards anticoagulant and specialized processing. In addition, the results of recombinant erythropoietin (r-EPO) clinical trials in neonates will be discussed.

Topics: Blood; Blood Donors; Blood Transfusion; Bloodletting; Cytomegalovirus Infections; Erythrocyte Transfusion; Erythrocyte Volume; Erythropoietin; Failure to Thrive; Graft vs Host Disease; Hematocrit; Humans; Infant, Low Birth Weight; Infant, Newborn; Jaundice, Neonatal; Oxygen; Recombinant Proteins; Transfusion Reaction

Topics: Age Factors; Blood Transfusion; Blood Volume; Bloodletting; Cell Separation; Child; Child, Preschool; Cytomegalovirus Infections; Erythropoietin; Graft vs Host Disease; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Leukocytes

The emergence of the acquired immunodeficiency syndrome (AIDS) has fueled concerns of both physicians and their patients about safety of blood transfusions. Although AIDS has generated the most fear, the risk today is extremely remote (1/60.000 units of blood). The risk of transmitting infectious disease by homologous transfusion is decreasing, as more donor screening and testing measures are implemented. The blood supply is safer that at any time, but small transfusion risks exist. The most common problems associated with transfusions are temporary: one in 100-300 recipients will experience fever or rash. The biggest problem is a mismatch of the well-known ABO blood groups and once in every 100-400.000 transfusions the hemolytic reaction is fatal. Viral hepatitis is another serious and important risk. At present hepatitis seems to strike between 1 and 3 percent of transfusion recipients. Most, if not all, of transfusion-associated hepatitis cases are caused by hepatitis C virus. Cytomegalovirus can cause primary infection, reactivation or reinfection by transfusion. Immunosuppressed patients are more likely to develop more severe disease. Epstein-Barr virus does not seem to cause significant post-transfusion disease. Bacterial or protozoal infections are an infrequently encountered adverse effect of transfusion. However, some clinical cases document the potential hazard of blood components as a vector for bacteria or protozoa. Homologous blood transfusion down-regulates some immune functions. Host defences against malignancy and infection may in some instances be severely compromised by transfusions of homologous blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Adult; Blood Donors; Blood Transfusion, Autologous; Deamino Arginine Vasopressin; Epoprostenol; Erythropoietin; Female; Graft vs Host Disease; Hemodilution; Hepatitis, Viral, Human; Humans; Infant, Newborn; Infections; Male; Pregnancy; Prognosis; Protozoan Infections; Risk Factors; Transfusion Reaction

Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with prolonged anemia caused by defective erythropoietin (Epo) production. We enrolled 34 recipients of an allogeneic HSCT in three consecutive trials to determine the optimal utilization of recombinant human erythropoietin (rhEpo) therapy in this setting.. In the first trial (n = 7), rhEpo 1400 U/kg/week was given from day 1 until a hemoglobin (Hb) level of 10 g/dL was achieved, for a maximum of 60 days. In the second trial, rhEpo 500 U/kg/week was given to achieve Hb levels of 13 to 14 g/dL in 13 anemic patients with fatigue 56 to 1440 days after transplant. In the third trial, rhEpo was scheduled to start on day 35 in 14 patients at a dose of 500 U/kg/week with the aim of achieving Hb levels of 13 to 14 g/dL.. In trial 1, erythroid recovery to 1% reticulocytes and red blood cell transfusion independence were faster, but the number of transfusions was not reduced compared to 10 controls. Responses were brisk in trial 2, with transfusion independence achieved after a median of 1 week in 12 of 13 patients, and 2-g Hb increments or Hb values of 11, 12, and 13 g/dL after 6, 7, 10, and 10 weeks, respectively. Transfusions were significantly reduced in the first month of rhEpo therapy. In trial 3, transfusion independence was obtained after a median of 1 week in 13 of 14 patients, and 2-g Hb increments or Hb values of 11, 12, and 13 g/dL after 3, 4, 6, and 8 weeks, respectively. Transfusions rates were considerably reduced compared to the previous month in the same patients or compared to controls undergoing peripheral blood or marrow transplant without rhEpo.. Anemia after allogeneic HSCT is exquisitely sensitive to rhEpo. The benefit is minimal when it is given early post-transplant, as used in all trials to date. However, the rate of major response is greater than 90% when rhEpo is started after day 35. These data provide the basis on which to conduct a prospective, randomized, placebo-controlled trial of rhEpo therapy after allogeneic HSCT.

Topics: Adolescent; Adult; Anemia, Aplastic; Bone Marrow Transplantation; Child; Cyclosporine; Drug Administration Schedule; Erythropoietin; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Leukemia; Lymphoma, Non-Hodgkin; Male; Middle Aged; Myelodysplastic Syndromes; Recombinant Proteins; Thrombocytosis; Transplantation, Homologous

Recombinant human erythropoietin (rHu EPO) has been reported to accelerate early erythroid reconstitution after bone marrow transplantation (BMT). We conducted a pilot study on rHu EPO for late-onset anemia in 9 patients after allogeneic BMT. The patients achieved initial erythropoietic recovery (hemoglobin (Hb) range 9.1-13.4, mean 10.8 g/dl), but then developed transplant-related anemia (Hb range 6.3-9.7, mean 8.2 g/dl) more than 50 days after BMT. This type of anemia was related to graft-versus-host disease (GVHD), cytomegalovirus infection, and/or impaired EPO secretion. The patients received 3,000 or 12,000 U of rHu EPO subcutaneously three or seven times weekly. Hb levels increased by more than 2 g/dl in 6 of the 9 patients, but were unchanged in the 3 patients with severe GVHD. These findings suggest that in some cases rHu EPO is effective for the treatment of late-onset anemia after BMT.

Topics: Adult; Anemia; Blood Transfusion; Bone Marrow Transplantation; Erythropoietin; Female; Graft vs Host Disease; Humans; Male; Recombinant Proteins; Time Factors; Transplantation, Homologous

We report on six cases of unrelated UCB transplant in adult patients with hematological malignancies: three chronic myelocytic leukemias and three acute leukemias. Their median age and body weight were respectively: 28 years (range 15.5-40) and 55.5 kg (range 46-90). The cord blood units were from the New York Blood Center. The median number of nuclear cells provided, evaluated before thawing, was 2.1 x 10(7)/kg (range 1 x 10(7)/kg-4.7 x 10(7)/kg). The degree of HLA disparity was 1/6: two patients, 2/6: three patients, 3/6: one patient. The patients received a pretransplant regimen including total body irradiation. They were given graft-versus-host disease prophylaxis which consisted of cyclosporin A and corticosteroids. They were all given a combination of G-CSF and erythropoietin. The median time of white blood cell and platelet reconstitution were respectively 24 days (range 12-43) and 60 days (range 23-90). All the patients had a full chimerism. A grade I acute GVHD was observed in four patients and two patients do not have any GVHD. No chronic GVHD has been observed yet. Three patients died from toxicity. Three patients are alive and well in complete remission at 2 years, 1 year and 11 months post-graft.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Burkitt Lymphoma; Cyclosporine; Erythropoietin; Female; Fetal Blood; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Immunosuppressive Agents; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male

Pluripotent stem cells of hematopoiesis and lymphopoiesis are among the CD34+ cells in blood or bone marrow. After granulocyte-colony stimulating factor (G-CSF) treatment, 1% to 2% of the mononuclear cells in blood are CD34+ cells, which can be procured by leukapheresis. We investigated the potential of CD34+ blood cells for reconstituting hematopoiesis and lymphopoiesis after allogeneic transplantation. HLA-identical sibling donors of 10 patients with hematologic malignancies were treated with G-CSF (filgrastim), 5 microgram/kg subcutaneously twice daily for 5 to 7 days. CD34+ cells were selected from the apheresis concentrates by immunoadsorption, concomitantly the number of T cells was reduced 100- to 1,000-fold. After transplantation, five patients received cyclosporine A for graft-versus-host disease (GvHD) prophylaxis (group I); five patients additionally received methotrexate (group II). G-CSF and erythropoietin were given to all patients. Mean numbers of 7.45 x 10(6) CD34+ and 1.2 x 10(6) CD3+ cells per kilogram were transplanted. In group I, the median times of neutrophil recovery to 100, 500, and 1,000 per mm3 were 10, 10, and 11 days, respectively. Group II patients reached these neutrophil levels after 10, 14, and 15 days, respectively. Platelet transfusions were administered for a median of 18 days in group I and 30 days in group II, and red blood cells for 9 and 12 days, respectively. Between day 30 and 60, lymphocytes reached levels of 353 +/- 269 cells per mm3. The median grades of acute GvHD were III in group I and I in group II. Two patients in group I died from acute GvHD. Two leukemic relapses occurred in group II. Complete and stable donor hematopoiesis was shown in all patients with a median follow up of 370 (45 to 481) days. Allogeneic blood CD34+ cells can successfully reconstitute hematopoiesis and lymphopoiesis. Reduction of T cells by CD34+ blood cell enrichment and cyclosporine A alone might not be sufficient for prophylaxis of severe acute GvHD.

Topics: Acute Disease; Adult; Antigens, CD34; Bone Marrow; Cell Division; Cyclosporine; Erythropoietin; Female; Filgrastim; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Immunosuppressive Agents; Leukapheresis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Male; Methotrexate; Middle Aged; Platelet Transfusion; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Recombinant Proteins; T-Lymphocytes; Transplantation, Homologous

Ninety one patients between the ages of 17 and 58 years undergoing histocompatible allogeneic transplants from sibling donors were entered into a double-blind randomised trial to evaluate the effect of human erythropoietin (rhu EPO) at a dose of 300 units per kg/day given thrice weekly by intravenous injection on erythropoiesis and on erythrocyte and platelet transfusion requirements. Dose was ceased when the haemoglobin exceeded 12g/dL and recommenced if the haemoglobin fell below 12 g/dL, at 150 units/kg/day. If the haemoglobin exceeded 12 g/dL on a further occasion, the dose of rhu EPO was not given. Patients received two units of erythrocytes when the haemoglobin dropped below 8.5g/dL and received platelet transfusions when the count dropped below 20 x 10(9)/L. Univariate analysis revealed a significantly higher reticulocyte count, haemoglobin concentration and bone marrow erythropoiesis after day 14 in the group receiving rhu EPO but this was not reflected in decreased erythrocyte transfusion (7 +/- 5 in controls versus 6 +/- 5 in rhu EPO group) or in platelet transfusions (11 +/- 7 in controls versus 11 +/- 9 in rhu EPO group). Hospitalisation in each group was the same (29 +/- 8 in the control group and 28 +/- 8 in the rhu EPO group). However, in the multivariate analysis, the administration of rhu EPO was associated with an 18% reduction in erythrocyte transfusion requirement when other variables were taken into account. No side-effects due to rhu EPO were detected in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Bone Marrow Examination; Bone Marrow Transplantation; Double-Blind Method; Erythrocyte Transfusion; Erythropoietin; Female; Graft vs Host Disease; Hemoglobins; HLA Antigens; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Nuclear Family; Platelet Transfusion; Prospective Studies

Inflammatory Bowel Disease (IBD) is recognized as a group of chronic inflammatory disorders, localized in the gastrointestinal tract, which does not have a cure known. Indeed, the pharmacological approaches, commonly used, demonstrate significant toxicity, which highlights the need of investigating new possible treatments. Erythropoietin (EPO) is clinically used in anemic patients, with chronic renal insufficiency, due to its erythropoietic effect. However, it has also been described other non-erythropoietic effects, such as an anti-inflammatory role. There is already preclinical evidence about its anti-inflammatory effect in the IBD context, namely in an acute model of colitis in mice. Therefore, it is relevant to ascertain its anti-inflammatory effect in a chronic model, but mainly its hematopoietic side effect, during chronic treatment.. This experiment aims to evaluate the efficacy and safety of EPO treatment in a chronic 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rodents.. The induction of chronic colitis consistedofn five weekly intrarectal administrations of 1% TNBS, and then mice were treated daily with 500 IU/Kg or 1000 IU/Kg of EPO, through intraperitoneal injections, for 14 days.. EPO demonstrated a significant anti-inflammatory effect, translated by a significant reduction of the concentration oftumorr necrosis factor-α, fecal calprotectin, and fecal hemoglobin. Moreover, it has also been demonstrated to be safe, considering the cardiovascular system, in terms of extraintestinal manifestations, namely at renal and hepatic functions.. EPO demonstrated to be a promising pharmacological approach to be considered in the management of IBD, being an interesting target for drug repositioning.

Topics: Animals; Anti-Inflammatory Agents; Chronic Disease; Colitis; Erythropoietin; Graft vs Host Disease; Inflammatory Bowel Diseases; Mice; Trinitrobenzenesulfonic Acid

Topics: Adult; C-Reactive Protein; Confounding Factors, Epidemiologic; Erythropoietin; Female; Ferritins; Glomerular Filtration Rate; Glucocorticoids; Graft vs Host Disease; Hemoglobins; Hepcidins; Humans; Immunosuppressive Agents; Insulin; Kidney Transplantation; Male; Middle Aged; Prednisolone

Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34

Topics: Adolescent; ADP-ribosyl Cyclase 1; Adult; Aged; Animals; Antigens, CD34; Cell Differentiation; Cell Movement; Chemokine CXCL12; Chimerism; Cohort Studies; Cord Blood Stem Cell Transplantation; Erythropoietin; Female; Graft vs Host Disease; Humans; Hyperbaric Oxygenation; Male; Mice; Middle Aged; Myeloid Cells; Receptors, Erythropoietin; Survival Analysis; Transplantation Conditioning; Treatment Outcome; Young Adult

Topics: Aged; Anemia, Hemolytic; Antibodies, Monoclonal, Murine-Derived; Darbepoetin alfa; Delayed Graft Function; Diagnosis, Differential; Erythropoietin; Female; Graft vs Host Disease; Hematinics; Hemolysis; Hemolytic-Uremic Syndrome; Humans; Immunologic Factors; Kidney Failure, Chronic; Kidney Transplantation; Rituximab

This 12th biannual report of the Cochrane Haematological Malignancies Group highlights recently published randomized controlled trials in the field of hemato-oncology, covering the publication period from September 1, 2009, through June 30, 2010. Implication for clinical practice and methodological aspects are the main principles used to select trials for this report. Studies on tyrosine kinase inhibitors for patients with chronic myeloid leukemia were identified through electronic search of MEDLINE with a broad search filter that covered all topics in hemato-oncology combined with a highly sensitive search filter for randomized studies as described in the Cochrane Handbook for Systematic Reviews of Interventions.

Topics: Adrenal Cortex Hormones; Aminoglycosides; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Cyclophosphamide; Dasatinib; Diphosphonates; Disease-Free Survival; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Gemtuzumab; Graft vs Host Disease; Hematologic Neoplasms; Hodgkin Disease; Humans; Imatinib Mesylate; Interferon-alpha; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Methotrexate; Piperazines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrimidines; Randomized Controlled Trials as Topic; Recombinant Proteins; Rituximab; Stem Cell Transplantation; Thiazoles; Treatment Outcome; Vidarabine

Topics: Aspartate Aminotransferases; Bone Marrow Transplantation; Child, Preschool; Combined Modality Therapy; Erythropoietin; Female; Ferritins; Graft vs Host Disease; Hemochromatosis; Humans; Leukemia, Myeloid, Acute; Liver Function Tests; Myelodysplastic Syndromes; Phlebotomy; Recombinant Proteins

Iron overload presenting as exacerbation of hepatic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation has not been previously described. We report 6 patients with established hepatic GVHD in whom iron overload (median serum ferritin, 7231 mug/dL; median transferrin saturation, 77%) resulting from a lifetime median of 20 units of packed red blood cell transfusions was manifested by worsening of liver function. Liver biopsies performed in 4 patients confirmed severe iron overload and also hepatic GVHD. Analysis for the C282Y and H63D hemochromatosis gene mutation was negative for the homozygous state in all 6 patients. Erythropoietin-assisted phlebotomy resulted in normalization of liver function at a median of 7 months and of serum ferritin at a median of 11 months. Immunosuppressive therapy was successfully tapered in all 4 patients who completed the phlebotomy program, and this supported the impression that iron overload, rather than GVHD, was the principal cause of liver dysfunction. At a median follow-up of 50 months (range, 18-76 months) from the transplantation and 25 months (range, 5-36 months) from ferritin normalization, all 4 patients require maintenance phlebotomy. We conclude that iron overload can mimic GVHD exacerbation, thus resulting in unnecessary continuation or intensification of immunosuppressive therapy for GVHD, and that maintenance phlebotomy is necessary after successful iron-reduction therapy.

Topics: Adult; Biopsy; Bone Marrow Transplantation; Combined Modality Therapy; Darbepoetin alfa; Diagnosis, Differential; Disease Progression; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Ferritins; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Iron Overload; Liver Diseases; Male; Middle Aged; Pancreatic Diseases; Phlebotomy; Prospective Studies; Recombinant Proteins; Skin Diseases; Transferrin; Transplantation Conditioning; Transplantation, Homologous

Current regular blood transfusion programs and chelation treatment have considerably improved survival of patients with thalassemia, which resulted in a larger proportion of adult patients. However, disease- and treatment-related complications in these patients progress over time, causing severe morbidity and shortened life expectancy. Stem cell transplantation still remains the only cure currently available for patients with thalassemia. This study updates transplant outcomes in 107 adult patients with median age of 22 years (range, 17-35 years) who received bone marrow transplantation (BMT) from human leukocyte antigen (HLA)-identical related donors between 1988 and 1996 (group A) and describes the results of BMT in 15 adult patients with median age of 21 years (range, 17-31 years) who were treated with a new treatment protocol (Protocol 26) between 1997 and 2003 (group B). The probability of survival, event-free survival, nonrejection mortality, and rejection for group A patients were 66%, 62%, 37%, and 4%, respectively, with a median follow-up of 12 years (range, 8.3-16.2 years). Group B patients treated with the new protocol had some improvement in thalassemia-free survival (67%) and lower transplant-related mortality (27%) than that of previous protocols. However, transplant-related mortality in these high-risk patients remains elevated. Current myeloablative BMT in adult patients is characterized by higher transplant-related toxicity due to an advanced phase of disease. Although this new approach to transplant adult patients with a reduced-dose intensity-conditioning regimen has improved thalassemia-free survival, transplant-related mortality in these high-risk patients remains elevated.

Topics: Adolescent; Adult; Azathioprine; Bone Marrow Transplantation; Busulfan; Chelation Therapy; Clinical Protocols; Combined Modality Therapy; Comorbidity; Deferoxamine; Disease-Free Survival; Erythrocyte Transfusion; Erythropoietin; Female; Follow-Up Studies; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Hemosiderosis; Humans; Hydroxyurea; Immunosuppressive Agents; Iron Chelating Agents; Life Tables; Liver Cirrhosis; Male; Phlebotomy; Postoperative Complications; Survival Analysis; Thalassemia; Transfusion Reaction; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine

Topics: Adolescent; Adult; Blood Donors; Busulfan; Child; Child, Preschool; Cyclosporine; Erythropoietin; Female; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Leukemia; Lymphoma; Lymphoproliferative Disorders; Male; Methotrexate; Middle Aged; Prednisolone; Whole-Body Irradiation

We studied 24 recipients of autologous bone marrow transplantation (ABMT) or allogeneic BMT (BMT) to determine whether impaired erythropoietin (Epo) response to anemia could delay full erythropoietic recovery. Observed Epo levels were compared with predicted levels based on the relationship between Epo and hematocrit in 125 control subjects. Circulating Epo levels were normal during conditioning and the early posttransplant period. Between days 21 and 180, Epo levels remained normal in ABMT patients but were inappropriately low for the degree of anemia in BMT patients. Median time to full erythropoietic engraftment was longer in BMT than in ABMT recipients. Circulating Epo returned to appropriate levels after day 180, except in patients with active cytomegalovirus infection. We conclude that impaired Epo response to anemia can contribute to delayed erythropoietic recovery after allogenic BMT. Renal toxicity of ciclosporin, interaction between host and donor marrow, and cytomegalovirus infection might play a role. This study could support the use of recombinant human Epo to accelerate erythropoietic engraftment after BMT.

Topics: Adolescent; Adult; Anemia; Bone Marrow Transplantation; Child; Child, Preschool; Cytomegalovirus Infections; Erythropoietin; Female; Graft Survival; Graft vs Host Disease; Hematocrit; Hematologic Diseases; Humans; Male; Middle Aged; Transplantation, Autologous; Transplantation, Homologous

Serum erythropoietin (EPO) levels were measured by radioimmunoassay in 36 patients undergoing allogeneic bone marrow transplantation (BMT). Serum EPO levels before conditioning treatment for BMT were generally higher than the levels obtained from healthy controls (49 +/- 17 (SEM) and 17 +/- 0.6, respectively). One day prior to BMT, after conditioning by chemotherapy with or without total body irradiation, the mean EPO level was markedly elevated (218 +/- 23 U/l, p less than 0.001) and reached to its highest level at 1 week post-BMT (269 +/- 40 U/l). Although, the EPO levels were significantly lower at 1 month (98 +/- 24 U/l, p less than 0.001), they were still elevated up to 3 months post-BMT, after which they gradually normalized. Patients given methotrexate and cyclosporine for prophylaxis against graft-versus-host disease (GVHD) had significantly lower EPO levels during the first 3 months post-BMT than patients transplanted with T cell-depleted marrow (p less than 0.05). Patients with post-transplant nephrotoxicity had lower, though not statistically significant, EPO levels than patients with normal renal function (p = 0.07). Acute GVHD and number of blood transfusions had no influence on serum EPO levels after BMT.

Topics: Adolescent; Adult; Bone Marrow Transplantation; Child; Child, Preschool; Creatinine; Cyclosporins; Erythropoietin; Female; Graft vs Host Disease; Humans; Kidney; Lymphocyte Depletion; Male; Middle Aged; T-Lymphocytes; Time Factors; Transplantation, Homologous

Serum obtained from (C3H X C57BL) F1 hybrid mice injected with parental (C57BL) lymph node cells after 600 rad irradiation contained a high level of an erythropoietic factor, which enhanced erythroid colony formation by fetal C57BL liver cells in methylcellulose cultures. The serum level of this erythroid colony-stimulating activity increased as the dose of lymph node cells injected increased and as suppression of endogenous spleen colonies (indicative of GVH severity) became more marked. Erythropoietin was also elevated in the sera of these mice. When these animals were transfused with washed packed red cells to induce plethora after sublethal irradiation and injection of lymph node cells, the erythropoietin level decreased, but erythroid colony-stimulating activity remained elevated. On the other hand, in anemic mice treated with phenylhydrazine, this erythropoietic factor was not detected, although the serum level of erythropoietin was elevated. These results suggest that a graft-versus-host (GVH) reaction may induce the production of an erythropoietic factor other than erythropoietin and that anemia itself may not be a stimulus for its in vivo production.

Topics: Anemia; Animals; Blood Transfusion; Cells, Cultured; Colony-Forming Units Assay; Colony-Stimulating Factors; Erythrocytes; Erythropoietin; Graft vs Host Disease; Hematopoietic Stem Cells; Liver; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Phenylhydrazines; Spleen