Miguel Angel Herrera-Rojas

Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults

Immune thrombocytopenia (ITP) results from platelet destruction and production suppression. Eltrombopag belongs to a new class of thrombopoietin-mimetic drugs that raise platelet counts in ITP patients. We performed a single-arm study to assess the response to a single course of dexamethasone (40 mg by mouth, days 1-4) in combination with eltrombopag (50 mg, days 5-32) in 12 adults with newly diagnosed ITP in an outpatient setting. Median follow-up was 12.5 months. After therapy (day 33), 100% of patients achieved at least ≥30 × 10(9)/L platelets. Four patients relapsed. Complete response at 6 months (platelets ≥100 × 10(9)/L) was achieved in 50% of patients and response at 6 months (platelets ≥30 <100 × 10(9)/L) was achieved in another 25%; relapse-free survival was 66.7% at 12 months (median response duration of 8.3 months). In conclusion, eltrombopag/dexamethasone is a feasible frontline therapy for ITP. This trial is registered at www.clinicaltrials.gov as NCT01652599.

Long-Term Insulin Independence in Type 1 Diabetes Mellitus Using a Simplified Autologous Stem Cell Transplant.

CONTEXT Efforts to find a cure for type 1 diabetes have focused on the removal of the autoimmune pathophysiologic substrate, with the use of immunosuppressive regimens including autologous hematopoietic stem cell transplantation (AHSCT). OBJECTIVE The main objective of determining long-term insulin independence as well as changes in glycated hemoglobin (HbA1c). Secondary outcomes were procedure morbidity and the need for hospital management. DESIGN We enrolled patients with type 1 diabetes between 2012 and 2014. Median follow-up was 34 months (range, 25-56 mo). SETTING Ambulatory care. INTERVENTIONS We decided to carry out an AHSCT protocol using a less toxic and affordable simplified method based on fludarabine in an outpatient setting. PATIENTS Patients were of both sexes, age 8-25 years, with positive levels of anti-GAD antibodies, a C-peptide level >1.0 ng/mL, and <3 months since diagnosis. MAIN OUTCOME MEASURE(S) Insulin independence. RESULTS Sixteen patients were included. Overall response was 81% with seven patients achieving insulin independence (44%); six were partial responders (37%) whereas three were nonresponders (19%). The HbA1c level showed a mean decrease of -2.3% at 6 months in the Insulin Independence group. Median age was 12 years old (range, 8-17 years old). A mean of 11.5 × 10(6) CD34+ cells (SD ± 8.2) was obtained. Related mortality at 100 days was 0% as well as during follow-up. Outpatient setting was 100%. CONCLUSIONS Simplified AHSCT in an outpatient setting is a feasible, safe and potentially therapeutic intervention for early-onset type 1 diabetes.

Combination of low-dose imatinib plus nilotinib for the treatment of chronic-phase chronic myeloid leukaemia after imatinib failure

Objectives: This is a feasibility study to evaluate whether simultaneous administration of low doses of imatinib and nilotinib in chronic-phase chronic myeloid leukaemia (CP-CML) patients has the potential for transcript elimination after failure to imatinib. Methods: Ten patients were enrolled; eight had cytogenetic relapse and two had confirmed loss of major molecular response (MMR). At baseline, BCR-ABL kinase domain mutation was detected in four patients. Results: After 6 months of therapy, major cytogenetic response, complete cytogenetic response, and MMR were achieved in seven, four, and four patients, respectively. Grade 4 thrombocytopenia developed in one patient, and grade 1 skin rash in four. Discussion and conclusion: These results suggest that imatinib might have inhibitory effects on the clearance of nilotinib, increasing its efficacy. This dual therapy was well tolerated and resulted in improvement of cytogenetic and molecular responses in patients with CP-CML after failure to imatinib. ClinicalTrials.gov registration number: NCT01819389.

Freezing the graft is not necessary for autotransplants for plasma cell myeloma and lymphomas

We studied rates of granulocyte and platelets recovery in 359 consecutive subjects receiving blood cell infusions in the context of autotransplants for plasma cell myeloma (N = 216) and lymphomas (N = 143). Blood cells were mobilised with filgrastim given for 4–5 days and collected after a median of 2 (range, 1–2) apheresis. Apheresis products were stored at 4° C for a median of 3 days (range, 2–6 days). Most subjects received carmustine, etoposide, cytarabine and melphalan (BEAM), cyclophosphamide, carmustine and etoposide (CBV) or high-dose melphalan. Filgrastim was given post transplant to 319 subjects. Median numbers of mononuclear cells collected was 31 × 10E + 6/kg (interquartile range (IQR) 37 × 10E + 6 cells/kg). Median numbers of CD34-positive cells collected was 3.6 × 10E + 6/kg (IQR 3.8 × 10E + 6/Kg). Median viability after collection was 90% (IQR 7%) after storage, 88% (IQR 12%). A total of 255 of 256 evaluable subjects recovered bone marrow function and there was no late bone marrow failure. Median interval to neutrophils >0.5 × E + 9/L was 13 days (range, 9–39 days) and to platelets >20 × 10E + 9/L, 16 days (range, 7–83 days). These rates and ranges seem comparable to those reported after autotransplants of frozen blood cells. There was no correlation between numbers of storage days at 4 °C and viability afte storage (r = −0.018, p = 0.14)) nor rates of recovery of neutrophils (r = −0.054, p = 0.52) or platelets (r = 0.116, p = 0.14). Blood cells collected for autotransplant can be stored at 4 °C for 6 d. This method is simple, inexpensive and widely applicable.

Reduced-intensity stem cell allografting for PNH patients in the eculizumab era: The Mexican experience

Abstract Background Paroxysmal nocturnal haemoglobinuria (PNH) presents as two major entities: the classical form, predominantly haemolytic and a secondary type with marrow failure and resultant aplastic anaemia (AA-PNH). Currently, the treatment of choice of the haemolytic variant is eculizumab; however, the most frequent form of PNH in México is AA-PNH. Patients and methods Six consecutive AA-PNH patients with HLA-identical siblings were allografted in two institutions in México, employing a reduced-intensity conditioning regimen for stem cell transplantation (RIST) conducted on an outpatient basis. Results Median age of the patients was 37 years (range 25–48). The patients were given a median of 5.4 × 106/kg allogeneic CD34(+) cells, using 1–3 apheresis procedures. Median time to achieve above 0.5 × 109/l granulocytes was 21 days, whereas median time to achieve above 20 × 109/l platelets was 17 days. Five patients are alive for 330–3150 days (median 1437) after the allograft. The 3150-day overall survival is 83.3%, whereas median survival has not been reached, being above 3150 days. Conclusion We have shown that hypoplastic PNH patients can be allografted safely using RIST and that the long-term results are adequate, the cost–benefit ratio of this treatment being reasonable. Additional studies are needed to confirm the usefulness of RIST in the treatment of AA-PNH.

Measurements of Catheter, Venous, and Capillary Cyclosporine A Blood Are Comparable and Useful in Pediatric Hematopoietic Stem Cell Transplant Recipients

before any procedure. Included were patients aged <18 years who had undergone a reduced-intensity conditioning HCT in an outpatient setting and received oral CsA as GVHD prophylaxis [7, 8] . All patients received oral doses of CsA (3–5 mg/kg b.i.d.) starting on the day before hematopoietic cell infusion. Venous blood samples were collected by conventional venipuncture at the cubital vein. Capillary samples were obtained by annular finger pricking using a Glucolet 2 automatic lancing device (Bayer, USA). Catheter samples were obtained by aspiration and/or port puncture through a port that had been previously placed for cell infusion or chemotherapy administration, regardless of the catheter type. Blood collected from the 3 sites was processed simultaneously within 2 h of collection with an Architect i1000SR immunoassay analyzer (Abbott Cyclosporine, Buenos Aires, Argentina). An Architect cyclosporine reagent kit and an Architect cyclosporine whole blood precipitation agent kit were used to determine CsA concentrations [9] . Acute and chronic graft-versus-host disease (GVHD) remains a common complication that occurs in 20–40% of patients during the first year after allogeneic hematopoietic cell transplantation (HCT) [1, 2] . Cyclosporine A (CsA) is one of the most common and effective drugs used to prevent GVHD [3, 4] . Studies comparing the results of different sampling sites for CsA determination have been carried out in patients receiving the drug via the intravenous route [5] ; in contrast, our patients are given oral CsA due to the lack of this drug in intravenous form in our country [6] . To our knowledge, there is no previously published information regarding capillary versus venous versus catheter blood samples in a pediatric HCT setting. We conducted a prospective comparative study at the Hematology Service of the Dr. José Eleuterio González University Hospital in Monterrey, Mexico. The hospital’s ethics committee approved the study protocol, and all patients and/or guardians gave written informed consent Received: October 11, 2016 Accepted after revision: December 18, 2016 Published online: February 23, 2017

No clinically relevant differences between capillary and venous blood cell counts in adult haematological patients using a nonautomated lancet

Sir, Physicians who treat patients suffering from haematological diseases require the determination of peripheral complete blood counts (CBC), among other tests, for making day-to-day therapeutic decisions. Venous values are accepted as the standard. The most common access site is a superficial arm vein. This situation can create problems: difficulty in finding a site for punctures, repeated attempts with considerable pain, phlebitis, haematoma and inadequate sampling. For these reasons, capillary CBC through finger pricking has been used an alternative in patients with blood sampling difficulties, particularly in infants and children. The successful use of this approach has been reported previously by many authors [1–6]. Samples are easily obtained and the results are quickly available, and trials from the last 10 years agree with the fact that capillary and venous blood CBC results are similar in both adults with haematological diseases and healthy controls; however, the procedure requires the use of an automated lancet to avoid operator mistakes. This procedure is painful, and the cost of the automated lancet is higher than that of a generic one. To our knowledge, there is no information regarding capillary vs. venous blood cell count in haematological patients using a nonautomated lancet. This prospective, comparative, single-arm study was performed between March 2013 and February 2014 in patients with haematological diseases who came to the haematology service of the University Hospital ‘Dr. Jos e Eleuterio Gonz alez’ in Monterrey, Mexico, for routine medical evaluation. Eligible patients were 18 years or older. Participants were excluded if they had an active infection, positive serology for HIV, hepatitis C, or B infections or were pregnant. Our institution’s ethics committee approved the study protocol, and all patients gave written informed consent before any procedure. Our primary outcome was the comparison between capillary and venous blood cell counts. Two blood samples were obtained from each patient at the same time; the first sample was obtained by puncture of a finger and the second sample was obtained by puncture of the antecubital vein. The procedure consisted in a finger prick on the lateral aspect of the pulp of the third or fourth finger of one hand, using a safety lancet (mediLance 3 mm blade, Monterrey, M exico); the first drop of blood was discarded to minimize excess tissue fluids. An aliquot of 200–500 lL of blood was collected in a tube with ethylenediaminetetraacetic acid (EDTA) for anticoagulation (BD Microtainer, NJ, USA). If necessary, the finger was gently massaged to obtain the required volume. Venous blood was procured from an antecubital vein into a vacuum tube (5 mL BD Vacutainer, Armonk, NY, USA) with EDTA. The punctures were performed by three operators (medical technicians) who attended the patients randomly. The same operator took capillary and venous blood samples from each subject. Both samples were assessed using the haematology analyser Sysmex XT-2000i (Sysmex, Kobe, Japan). Results are presented as means with standard deviation, among other central tendency measures. Venous and capillary measurements were contrasted according to the normality in the Kolmogorov–Smirnov test using either Student’s t-test or analysis of variance (ANOVA) for paired samples. Correlations between capillary and venous samples were determined using Spearman or Pearson’s tests according to the normality as well. Cohen’s kappa was obtained in order to compare each sample’s ability to diagnose low, normal or high values in each variable according to our laboratory’s reference values. Table 2 notes. Specificity was calculated by dividing ‘true-negative’ capillary results (i.e. normal capillary results confirmed in venous testing) by all negative results in the venous sample. The relation between ‘truepositive’ (i.e. altered capillary results confirmed in venous testing) and all altered venous values determined sensitivity. A P-value of 0.05 was considered significant, and all tests were two-sided. Statistical analysis was performed using SPSS software version 20.0 for Mac (IBM, Armonk, NY, USA). We included 107 patients, 15 were excluded from the analysis; three were considered healthy and 12 because their samples were taken by two different operators. Ninety-two patients were analysed. The median age was