Allogeneic stem cell transplantation for patients with chronic myeloid leukemia: Risk stratified approach with a long-term follow-up

The use of allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) was almost abandoned in recent years for very effective targeted therapy with tyrosine kinase inhibitors (TKIs). However, approximately one third of patients still need another treatment including SCT. 38 consecutive CML patients were treated (most in preimatinib era) with allogeneic SCT, using partial T cell depletion (TCD) and preemptive donor lymphocyte infusion (DLI), without post‐transplant graft‐versus‐host disease (GvHD) prophylaxis. Conditioning included busulfan, cyclophosphamide, antithymocytic globulin, and fludarabine followed by donor stem cell transfusion. With a median follow up of 90.5 months (1–134), 32 patients are alive. 97% engrafted. 5‐year leukemia free survival (LFS) and overall survival (OS) were 78.95% and 84.2%, respectively. All patients are in major molecular remission and 78% in complete molecular remission. Transplant‐related mortality (TRM) was 13%. Twenty‐four patients received DLI for residual disease. Acute GvHD, mostly Grades I‐II, occurred in 18% of patients post‐transplant and in 24% of patients receiving DLI. In conclusion, the risk‐adapted approach using only partial TCD and preemptive escalated dose of DLI precluded the need for immunosuppressive medications and reduced the risk of significant GvHD without compromising engraftment and long‐term disease control. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.     

Hematopoietic stem cell transplantation across major genetic barriers

The first successful demonstration that effective T cell depletion can enable immune reconstitution without causing graft versus host disease (GVHD) was achieved in 1980 using lectin-separated hematopoietic stem cells. In leukemia patients undergoing supralethal radio- and chemotherapy, T cell-depleted transplants are vigorously rejected by residual host T cells; this barrier was first overcome in 1993 by the use of megadose stem cell transplants. This clinical observation can be explained, in part, by the demonstration that cells within the CD34 compartments, as well as their immediate early myeloid progeny, are endowed with veto activity. Engraftment of mismatched hematopoietic stem cells following reduced intensity conditioning, still represents a major challenge. Progress has been made recently by using anti-3rd party veto CTLs and T regulatory cells. Plenary lecture: Inaugural meeting of the Robert A. Good Immunology Society, June 9–11, 2006, Tampa, Florida. Presented at the First Robert A Good Society Symposium, St. Petersburg, FL 2006.     

Pulmonary hypertension in patients with end-stage renal disease

BACKGROUND: The aims of this study were to evaluate the incidence of unexplained pulmonary hypertension (PH) among patients with end-stage renal disease (ESRD) and to suggest possible etiologic factors. METHODS: The incidence of PH was prospectively estimated by Doppler echocardiography in 58 patients with ESRD receiving long-term hemodialysis via arteriovenous access, and in control groups of 5 patients receiving peritoneal dialysis (PD) and 12 predialysis patients without a known other cause to suggest the presence of PH. Clinical variables were compared between patients with and without PH receiving hemodialysis. Changes in pulmonary artery pressure (PAP) values before and after onset of hemodialysis via arteriovenous access, arteriovenous access compression, and successful kidney transplantation were recorded. RESULTS: PH > 35 mm Hg was found in 39.7% of patients receiving hemodialysis (mean +/- SD, 44 +/- 7 mm Hg; range, 37 to 65 mm Hg), in none of the patients receiving PD, and in 1 of 12 predialysis patients. Patients with PH receiving hemodialysis had a significantly higher cardiac output (6.9 L/min vs 5.5 L/min, p = 0.017). PH developed in four of six patients with normal PAP after onset of hemodialysis therapy via arteriovenous access. One-minute arteriovenous access compression in four patients decreased the mean systolic PAP from 52 +/- 7 to 41 +/- 4 mm Hg (p = 0.024). PH normalized in four of five patients receiving hemodialysis following kidney transplantation. Kaplan-Meier survival analysis according to PAP values revealed significant survival differences (p < 0.024). CONCLUSIONS: This study demonstrates a surprisingly high incidence of PH among patients with ESRD receiving long-term hemodialysis with surgical arteriovenous access. Both ESRD and long-term hemodialysis via arteriovenous access may be involved in the pathogenesis of PH by affecting pulmonary vascular resistance and cardiac output.     

Successful haploidentical bone marrow transplantation in Fanconi anemia

A 10-year-old girl with Fanconi anemia and severe aplastic anemia underwent a haploidentical BMT from her mother due to lack of a matched family donor. T cell depletion was done by positive selection of CD34 cells with immunomagnetic beads. Due to graft rejection a second haploidentical BMT from the father was successfully undertaken. No immunosuppression was given after the transplant. Immunological reconstitution took approximately 6 months, with no GVHD or severe infections. Such a transplant, containing a large purified CD34 cell fraction with a minimal number of added T cells, should be considered as the treatment of choice for patients with Fanconi anemia if no HLA matched donor is available.     

Prospective study of IgM to Toxoplasma gondii on Beckman Coulter's Access(TM) immunoassay system and comparison with Zeus ELISA and gull IFA assays

We compared a new assay for Toxoplasma IgM on the Access analyzer (Beckman Coulter, Inc., Chaska, MN, USA), a random access instrument based on the principle of paramagnetic particle enzyme immunoassay with an enzyme-linked immunosorbent assay (ELISA) (Zeus Scientific, Inc., Raritan, NJ, USA) and an immunofluorescent assay (IFA) (Gull Laboratories, Inc., Salt Lake City, UT, USA). Four hundred fresh, unfrozen clinical samples from pregnant women (n = 154), HIV positive patients (n = 41), and patients in whom infection with Toxoplasma gondii was suspected (n = 200) were collected and assayed over a three month period. The specificity of the Access assay was compared to the consensus results. Results that were discrepant between the ELISA and IFA were resolved using a third IFA (Zeus). Once resolved, the specificity for the Access assay, the Zeus ELISA and the Gull IFA were 99.22%, 97.91%, and 99.45%, respectively. We conclude that the Access assay specificity is comparable to consensus results, minimizing false positive results; and because it is a random access instrument, it may be preferable over batch methods.     

Real-time echo-Doppler Duplex Scanner in the evaluation of patients with Poland sequence

In two neonates with partial Poland sequence, an infant with complete Poland sequence and his mother subclavian artery diameter and its flow velocity waveforms were determined by real-time echo-Doppler Duplex Scanner. These measurements were significantly lower than on the normal side in the same patient. Subclavian hypoplasia appears as a local vascular defect which, in addition to thoracic muscle defects and bone defects of the hand, may be one of the main components of the Poland sequence.