Guillermo J. Ruiz-Delgado

Dimethyl Sulfoxide-Induced Toxicity in Cord Blood Stem Cell Transplantation: Report of Three Cases and Review of the Literature

Umbilical cord blood transplantation using nonmyeloablative conditioning is currently considered by many as a valid potential alternative for any patient who requires an unrelated donor allograft and who is without a suitably matched and readily available volunteer. Dimethyl sulfoxide (DMSO) has been used for years as a cryoprotectant agent; it acts by penetrating the cell and binding water molecules and it has been described as harmless for the individual who receives it in limited amounts. In this paper, we describe 3 cases of DMSO-induced toxicities and briefly review the most common adverse reactions of the DMSO when used as a cryopreservation agent for the long-term storage of cord blood cells. Two of the 3 cases had a dismal prognosis. A brief review of the literature is presented.

A simplified method for stem cell autografting in multiple myeloma: a single institution experience

In a 14-year period in a single institution 31 autografts were performed in 26 patients with multiple myeloma (MM), using a simplified and affordable autografting procedure: conducting the grafts on an outpatient basis and avoiding stem cell freezing. Autografts were started on an outpatient basis in all instances, but four patients were admitted to the hospital. Median time to achieve more than 0.5 × 109/l granulocytes was 27 days, whereas median time to recover above 20 × 109/l plts was 37 days. CR was achieved in 19 cases and a very good partial response in 6 cases. The 100-day mortality was 9.6%. The overall median post-transplant survival has not been reached, being above 76 months, whereas the 76-month survival is 80%. The median cost of each procedure was US

Results of an Autologous Noncryopreserved, Unmanipulated Peripheral Blood Hematopoietic Stem Cell Transplant Program: A Single-Institution, 10-Year Experience

15 000. Survival results were substantially better than those of historical control in a group of patients treated in the same institution with melphalan/prednisone. It is concluded that high-dose therapy rescued with a simplified autologous stem cell graft is a valid, useful and affordable therapeutic option for patients with MM, even with economical restraints.

More on Geographic Hematology: The Breakpoint Cluster Regions of the PML/RARα Fusion Gene in Mexican Mestizo Patients with Promyelocytic Leukemia are Different from Those in Caucasians

Background: Methods to simplify the stem cell transplantation procedures are needed mainly in developing countries. We have previously shown that unprocessed leukapheresis material is useful to restore hematopoiesis after high-dose chemotherapy. Methods: Over a 10-year period in a private practice setting, we prospectively performed autotransplants using noncryopreserved and unmanipulated peripheral blood stem cells mobilized from the bone marrow to the peripheral blood by means of filgrastim and using a single-day conditioning regimen with high dose (200 mg/m2) melphalan. Results: Forty-six individuals were given 50 autografts. The median age of the patients was 33 years (range 8–69). Twenty-two patients with acute leukemia (13 with myeloblastic and 9 with lymphoblastic leukemia), 4 with chronic myelogenous leukemia, 6 with multiple myeloma, 7 with Hodgkin’s disease, 3 with non-Hodgkin’s lymphoma and 4 with metastatic breast carcinoma were included. The median time to achieve >0.5 × 109/l granulocytes was 14 days (range 0–86), whereas the median time to achieve >20 × 109/l platelets was 25 days (range 0–102). The 3,300-day posttransplant survival was 63%, the median posttransplant overall survival was over 3,300 days, the 3,300-day disease-free survival was 50% and the transplant-related mortality was 2%. The procedure was performed entirely on an outpatient basis in the case of 48 autografts (96%). The approximate cost of each graft was 7,500 USD. Conclusion: This simplified method to autograft patients, avoiding in-hospital stays, purging procedures and cryopreservation of the cells, is feasible and results in a substantial decrease in the cost of the autologous hematopoietic stem cell transplantation methods.

High response rate to low-dose rituximab plus high-dose dexamethasone as frontline therapy in adult patients with primary immune thrombocytopenia

Acute promyelocytic leukemia is characterized the PML/RARalpha chimeric fusion gene, transcript and protein; the breakpoint cluster regions (bcr) in the PML gene may occur in 3 different sites: Intron 6 (bcr1), exon 6 (bcr2) or intron 3 (bcr3). In a 10-year period in a single institution, we studied prospectively the breakpoint cluster regions of the PML/RARalpha fusion gene in 43 Mexican Mestizo patients with APL, and found that the bcr1 represented 62.7%, the bcr2 9.3% whereas the bcr3 27.9%. The prevalence of the bcr1 subtype is significantly higher than that informed in Caucasians and similar to that in Asians; these data are consonant with those described in other Latin-American patients with APL. Since other Asian genetic markers have been found in the Indian component of the Mexican mestizos, it is possible that the Asian immigration into the Americas through the strait of Behring 12,000 years ago may account for a possible genetic susceptibility to suffer certain forms of APL.

Abnormalities in the expression of CD55 and CD59 surface molecules on peripheral blood cells are not specific to paroxysmal nocturnal hemoglobinuria

Corticosteroids as initial therapy for primary immune thrombocytopenia achieve a low rate of sustained remission.

Outpatient allografting using non-myeloablative conditioning: the Mexican experience.

Abstract The regulatory proteins CD55 and CD59 are glycolsylphosphatidylinositol-anchored, type I cell surface proteins, which inhibit formation of the C3 convertases and prevent the terminal polymerization of the membrane attack complexes, respectively. Paroxysmal nocturnal hemoglobinuria (PNH) is a genetic disorder due to the impaired conformation of the glycolsylphosphatidylinositol anchor, which results in the deficient expression of CD55 and CD59 leading to excessive destruction of red cells and leukocytes. We have studied the expression of these two molecules in red blood cells, granulocytes and platelets in patients with PNH (two patients), autoimmune hemolytic anemia (AIHA) (seven patients), autoimmune thrombocytopenia (ATP) (22 patients), systemic lupus erythematosus (SLE) (19 patients), aplastic anemia (AA) (eight patients), and Evans syndrome (ES) (two patients). A diminished expression of CD55 and CD59 was found in the three cell lines of the two patients with PNH. In the seven patients with AIHA two were found with CD59 diminished expression in red blood cells and one with CD59 diminished expression in granulocytes. In the patients with ATP one was found with CD55 diminished expression in red blood cells, one with CD59 diminished expression granulocytes and one with a CD59 diminished expression in the platelets. In the subset of patients with SLE only one was found with a CD55 diminished expression in the red blood cells. In the patients with AA, a diminished expression in red blood cells was not found; however, one patient was found with a diminished expression of CD59 in granulocytes, and one patient with a diminished expression of CD55 in the platelets. In the two patients with ES we did not found changes in the expression of CD55 and CD59. We conclude that the diminished expression of the glycolsylphosphatidylinositol-anchored type I cell surface proteins CD55 and CD59 is not specific to PNH and that it can be found in patients with a variety of autoimmune disorders. Additional studies are needed to define the role of the deficiencies of CD55 and CD59 in the pathogenesis of autoimmune hemocytopenias.

Ineffectiveness of oral iron hydroxide polymaltose in iron-deficiency anemia.

A group of 132 patients with both malignant and nonmalignant conditions was allografted using the ‘Mexican’ method of non-ablative conditioning. The conditioning was delivered on an outpatient basis and the procedure was planned to be conducted on outpatients in all cases. While 103 patients (78%) were able to complete the procedure totally as outpatients, 29 (22%) were hospitalized because of fever, mucositis or acute graft-versus-host disease. In a multivariate analysis, although differences were not statistically significant, it was found that the patients who were allografted as outpatients had higher levels of hemoglobin (12 versus 11.8 g/dl), higher platelet counts (248 versus 191 × 109/l), lower white blood cell counts (11.7 versus 12.4 × 109/l), higher Karnofsky scale scores (100 versus 90%) and lower creatinine levels (0.9 versus 0.93 mg/dl). A total of 86% of the patients with normal values for these variables could be allografted as outpatients, whereas only 67% of those with abnormal values completed the entire procedure as outpatients. It is concluded that allografting can be accomplished totally on an outpatient basis using the ‘Mexican’ reduced intensity-conditioning regimen.

Outcome of adults with acute lymphoblastic leukemia treated with a pediatric-inspired therapy: a single institution experience

Abstract Two hundred and forty one patients with iron deficiency anemia (IDA) were identified in a single institution over a 24-year period; of these, 75 individuals were studied as the result of persistent IDA despite the administration of oral iron hydroxide polymatose (IP). The levels of hemoglobin when the patients were referred for study after being given oral IP had a median of 10.3 g/dl; after administration of oral iron fumarate during periods ranging from 1 to 14 months, the levels of hemoglobin rose to a median of 12.5 g/dl (p > 0.01). Our data support previous observations made in other countries about the ineffectiveness of oral IP in the treatment of individuals with IDA and should alert the clinician to avoid unnecessary consultations and misdiagnosis.

Low incidence and severity of graft-versus-host disease after outpatient allogeneic peripheral blood stem cell transplantation employing a reduced-intensity conditioning

Today, long-term survival is achieved in more than 80% of children aged 1–10 years with acute lymphoblastic leukemia (ALL). However, cure rates for adults, adolescents, and young adults remain relatively low, at only 40–50%. Adult regimens are typically less intense than their pediatric counterparts, because it is thought that adults do not tolerate drugs utilized in ALL treatment as well as children do. Adolescents with ALL have a better outcome when treated with pediatric protocols compared to adult protocols [1–3], and there are also suggestions of improved outcomes of adult patients with ALL treated with pediatric-inspired chemotherapy schedules [4]. Whether these improved outcomes are a result of higher doses of non-myelosuppressive drugs or whether they relate to other factors such as the experience of physicians or stricter adherence to scheduled treatments is unclear. We have tested the usefulness of an asparaginase-containing, pediatric chemotherapy-inspired protocol to treat adults with ALL, and report herein our results in a group of 80 patients studied and treated in a single institution during a 16-year period. All consecutive adult (18 years or older) patients with ALL studied and treated after March 1994 were prospectively included in the study. Patients were treated with a modification of the St. Jude Total XI combined chemotherapy program [5,6]; this schedule has an acceptable toxicity, employs affordable drugs, and can be delivered as an outpatient regimen, thus resulting in diminished costs. Induction was done with oral prednisone (40 mg/m/day6 28 days), intravenous (IV) vincristine (1.4 mg/m, capped to 2 mg, days 1, 8, 15, and 22), IV daunomycin (25 mg/m days 1, 8, and 15), intramuscular (IM) L-asparaginase (10 000 U/m days 4, 10, 15, and 19), IV etoposide (200 mg/ m days 22 and 29), and IV cytarabine (300 mg/m days 22, and 29). As consolidation therapy, IV methotrexate (MTX, 2.0 g/m, 2 h infusion, days 44 and 51) with oral folinic acid rescue (10 mg/m every 4 h, 612) was employed. Patients who did not attain complete remission (CR) after induction/consolidation were taken out of the study. The regimen of the early treatment is shown in Table I. As continuation therapy, oral 6-mercaptopurine (50 mg/ m/day) and oral MTX (20 mg/m/week) were employed, in addition to monthly pulses of rotating combinations of the drugs employed during induction (vincristineþdaunomycinþ asparaginase63 weekly doses; etoposideþ cytarabine62 weekly doses; methotrexateþ folinic acid61). Triple intrathecal therapy (MTX, dexamethasone, and cytarabine) was delivered on days 22 and 43 during induction and every 8 weeks along maintenance therapy, which was extended for 24 months. After June 2001 (when tyrosine kinase inhibitors [TKIs] became available in Mexico), Philadelphia chromosome-bearing (Ph1þ) patients were given imatinib (400 mg/day) or dasatinib (100 mg/day) 7 days after starting chemotherapy, and were assessed for stem cell transplant (SCT) once they achieved a