Self-reported changes in the expanded disability status scale score in patients with multiple sclerosis after autologous stem cell transplants: real-world data from a single center.

In order to reset the immune system to baseline function, autologous hematopoietic stem cell transplantation (HSCT) has been performed in patients with multiple sclerosis (MS). After June 2015, 617 new consecutive patients with MS were autografted in our center with non-frozen peripheral blood stem cells. The autografts were performed on an out-patient basis, after conditioning with cyclophosphamide and rituximab. The aim of the study was the assessment of both safety and efficacy of the method. The study's primary co-end-points were recovery of granulocyte and platelet counts and transplant-related mortality. Secondary end-points were overall survival and clinical response (improvement or stabilization of the self-reported expanded disability status scale score). The protocol was registered in ClinicalTrials.gov identifier NCT02674217.0. We included 401 females and 216 males, with a median age of 46 years. A total of 259 patients had relapsing-remitting MS (RRMS), 228 had secondary progressive (SPMS) and 130 had primary progressive (PPMS) multiple sclerosis. All procedures were initially performed on an out-patient basis and only 32 individuals (5%) required hospitalization. One to three aphereses (median 1) were required to harvest at least 1 × 106 /kg viable CD34+ cells. The total number of viable CD34+ infused cells ranged between 1 and 37·83 × 106 /kg (median 5·68). Patients recovered more than 0·5 × 109 /l absolute granulocytes by day 8 (median, range = 2-14), and platelet values were above 20 × 109 /l by day 4 (median, range = 0-11). Eleven individuals required red blood cells and six needed platelet transfusions. To date, there have been no deaths attributable to the transplant, yielding a 30-month overall survival of 100%. Patients have been followed for 3-42 months (median = 12). The overall response rate (decrease or stabilization of the self-reported EDSS score) at 12 months was 78% for all patients (83% in RRMS, 78% in PPMS and 73% in SPMS), while the disability progression-free survival was 82% for all patients (86% in RRMS, 78·5% in SPMS and 78% in SPMS). Changes in the self-reported EDSS score in parallel with neurological improvement were observed in people with all types of MS after HSCT, employing the 'Mexican method'.

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 x 10(9)/l granulocytes was 27 days, whereas median time to recover above 20 x 10(9)/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$ 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.

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

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 x 10(9)/l), lower white blood cell counts (11.7 versus 12.4 x 10(9)/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.

Autologous peripheral blood stem cell transplantation in multiple myeloma using oral versus I.V. melphalan.

Autologous peripheral blood stem cell transplantation is the therapy of choice for the treatment of multiple myeloma (MM) patients younger than 70 years old. Between August 1993 and November 2004, 54 patients with MM were autografted after conditioning with high-dose oral melphalan 140 mg/m(2) in combination with etoposide and carmustine (28 patients) or with high-dose melphalan 200 mg/m(2) I.V. (26 patients). The oral and IV melphalan groups were comparable. There were no significant differences in disease-free survival (DFS) and overall survival (OS) between the groups; however, in patients transplanted in remission, OS and DFS were better in the I.V. melphalan group. Four good-prognostic factors were identified: interval between diagnosis and transplant <18 months, number of prior chemotherapy lines < or =2, remission status (complete or partial), and the use of I.V. melphalan. In conclusion, I.V. melphalan is the therapy of choice for conditioning patients with MM who are in remission.

Heterozygosity for the H63D mutation in the hereditary hemochromatosis (HFE) gene may lead into severe iron overload in beta-thalassemia minor: observations in a thalassemic kindred.

Heterozygosity for beta-thalassemia (minor) by itself does not lead into iron overload; however, when it is inherited together with a homozygous state for either the H63D or the C282Y mutations of the hereditary hemochromatosis gene (HFE gene), iron overload may ensue. We describe here a kindred in which the propositus, being heterozygote for beta-thalassemia and the H63D mutation of the HFE gene, developed severe iron overload and in turn, chronic liver failure with portal hypertension. Other members of the family with either beta-thalassemia or heterozygous for the H63D gene mutation did not develop iron overload. The interaction between beta-thalassemia and hereditary hemochromatosis is briefly discussed and speculations about other possible genetic mutations leading into familial iron loading are done.

Are there "Attenuated" Forms of Evans Syndrome?

Indirect evidence of hemolysis has been described in patients with autoimmune thrombocytopenic purpura. In order to collect more data, another method to assess red blood cell destruction in these patients was employed: measurement of free haptoglobin levels. In 17 individuals with autoimmune thrombocytopenic purpura the levels of free haptoglobins were assessed after carefully ruling out microangiopathic hemolysis, systemic lupus erythematosus or overt Evans syndrome. Abnormally low levels of free haptoglobins were found in five individuals (29%) as indirect evidence of hemolysis. The long-term thrombocytopenia-free status was lower in patients with low haptoglobin levels than in those with normal levels (40 versus 58%). These data, added to previous evidence, support the observation of Evans made 50 years ago: "there is a spectrum-like relationship between primary thrombocytopenia and haemolytic anemia".". Accordingly, the concept of "attenuated" variants of the Evans syndrome could be entertained.

PML/RAR alpha(+) hypergranular acute promyelocytic leukemia (M3) developing into an M3 acute myelocytic leukemia without PML/RAR alpha.

The case of an adult with PML/RARalpha(+) hypergranular acute promyelocytic leukemia (M3) that evolved into a rapidly fatal M3 acute myelocytic leukemia without PML/RARalpha after a complete and molecular remission had been achieved, is presented. Only 7 such cases have been published in the literature. The possible origin of this either leukemic relapse or secondary malignancy is briefly discussed, focusing on the fact that this diagnosis could only be defined by adequate molecular biology studies in the leukemic cells.

The G20210A polymorphism in the 3'-untranslated region of the prothrombin gene in Mexican mestizo patients with primary antiphospholipid syndrome.

In an effort to identify alleles associated with an increased risk of venous thrombosis in patients with primary antiphospholipid syndrome, we studied the G20210A polymorphism (the G-->A mutation at nucleotide position 20210) in the 3'-untranslated region of the prothrombin gene in a group of 14 patients with primary antiphospholipid syndrome. We did not find any patient with the mutated gene. Since the prothrombin mutation is more prevalent in white populations, this finding may be related with the genetic composition of the Mexican mestizos, in whom the white component is low. The polymorphism of the prothrombin gene in Mexican mestizo patients with antiphospholipid syndrome does not seem to be related to the thrombophilia observed in these patients.