Lucien Noens

Early immunosuppression withdrawal after living donor liver transplantation and donor stem cell infusion

Long‐term results of organ transplantation are still limited by serious side effects of immunosuppressive drugs. A major issue, therefore, is to elaborate novel therapeutic protocols allowing withdrawal or minimization of immunosuppressive therapy after transplantation. We report on 3 patients prospectively enrolled in an original protocol designed to promote graft acceptance in living donor liver transplantation, using posttransplant conditioning with high doses of antithymocyte globulin followed by injection of donor‐derived stem cells. In 2 patients, early immunosuppression withdrawal was possible, without subsequent graft deterioration. In these 2 cases, in vitro studies showed indices of immunological tolerance as assessed by specific hyporesponsiveness to donor alloantigens in mixed lymphocytes culture. In the third patient, acute rejection rapidly occurred after discontinuation of immunosuppression, and minimal immunosuppression has to be maintained during long‐term follow‐up. In this case, a clearly distinct immunoreactive profile was observed as compared to tolerant patients, as no specific modulation of the antidonor response was observed in vitro. Of note, no macrochimerism could be detected in any of the 3 patients during the follow‐up. In conclusion, these clinical observations demonstrated that, despite the absence of macrochimerism, donor stem cells infusion combined with recipient conditioning may allow early immunosuppression withdrawal or minimization after liver transplantation. Liver Transpt 12:1523–1528, 2006.

ABO-mismatch adult living donor liver transplantation using antigen-specific immunoadsorption and quadruple immunosuppression without splenectomy.

ABO‐incompatible (ABO‐I) liver transplantation is a controversial issue because of the generally less favorable outcome as compared to compatible transplants. Encouraging results have been shown by the introduction of new strategies to reduce posttransplant‐specific hemagglutinin (HA) titers with plasmapheresis, reinforced immunosuppression (IS), and the use of splenectomy. We describe a new protocol consisting of daclizumab (DAC) induction, mycophenolate mofetil (MMF)/tacrolimus (TAC)/steroids without splenectomy. Five recipients (mean age of 47 ± 14 yr) undergoing ABO‐I living donor liver transplantation (LDLT) were included in this protocol. Immunoadsorbent columns (Glycosorb ABO) were used for antigen‐specific immunoadsorption (ASI). The median follow‐up was 18.5 ± 10.5 months. ASI was very efficient in lowering HA titers (mean log2 immunoglobulin [Ig] M [IgM] and IgG values before and after ASI were 5.9 ± 2.8 and 1.2 ± 1.4 [P= 0.0038] and 6.5 ± 2.3 and 1.1± 1.9, respectively [P= 0.0001]). Persisting low HA titers were observed over time. No sepsis nor cytomegalovirus infection episodes were recorded. Acute cellular rejection (ACR) occurred in 1 recipient responding to steroid pulse therapy. Two grafts were lost in 2 patients due to technical failure during the first postoperative month. We conclude that ASI using Glycosorb ABO, quadruple immunosuppression including DAC and MMF provide high efficiency to lower HA titers over time, avoiding the need for splenectomy. ABO‐I LDLT can be performed with this adapted IS protocol. Liver Transpl 12:1412‐1417, 2006.

Long-term survival data from a phase 3 study of Filgrastim as an adjunct to chemotherapy in adults with de novo acute myeloid leukemia

We previously reported the results of a double-blind, placebo-controlled study of Filgrastim in patients with de novo AML undergoing induction and consolidation chemotherapy. The study demonstrated that Filgrastim was effective and well tolerated and had no impact on complete remission or survival. We now report follow-up data on these patients, assessing long-term effects with emphasis on prognostic indicators. After a median follow-up of 7 years, 434 (83%) patients were dead, 73 (14%) were alive, and 14 (3%) were lost to follow-up. The proportions of deaths were similar in the Filgrastim (83%) and placebo (84%) groups. No differences in median time to death (1.04 years Filgrastim, 1.13 years placebo; P=0.97) or median disease-free survival (0.86 years Filgrastim, 0.79 years placebo; P=0.52) were evident. Proportional hazard modeling identified age, performance status, and French-American-British subtype as independent predictors for survival (P<0.001, P=0.005, and P=0.036, respectively), whereas cytogenetic status was not (P=0.118). Filgrastim had no effect on overall survival in any of these subgroup analyses as none of the treatment comparisons were statistically significant. These findings indicate that Filgrastim can be effectively used to support patients with AML undergoing induction and consolidation chemotherapy without worsening long-term disease outcome.

Pyoderma gangrenosum as an Early Revelator of Acute Leukemia

Bullous pyoderma gangrenosum is an atypical, more superficial variety of the classical pyoderma and is often associated with myeloproliferative disorders. We present the case of a patient who presented initially with subcutaneous nodules and who developed bullous lesions afterwards. Histological evaluation showed the presence of neutrophilic infiltrates in both lesions. A few months after the diagnosis of bullous pyoderma gangrenosum, an underlying leukemia was revealed. Our case illustrates the importance of regular blood and bone marrow examinations in patients with atypical bullous pyoderma gangrenosum, resulting in a rapid diagnosis of the underlying disease.

Guidelines for the transfusion of platelets.

Abstract Recommendations aiming at standardising and rationalising clinical indications for the transfusion of platelets in Belgium were drawn up by a working group of the Superior Health Council. To this end the Superior Health Council organised an expert meeting devoted to “Guidelines for the transfusion of platelets” in collaboration with the Belgian Hematological Society. The experts discussed the indications for platelet transfusions, the ideal platelet concentrate and the optimal platelet transfusion therapy. The recommendations prepared by the experts were validated by the working group with the purpose of harmonising platelet transfusion in Belgian hospitals.

Erythromelalgia: a clue to the diagnosis of polycythemia vera.

We report the case of a 74-year-old woman with recurrent episodes of symmetrical congestion and erythema in the distal lower legs causing a burning distress. Laboratory and clinical investigations revealed an underlying myeloproliferative disorder. The cutaneous symptoms were atypical of erythromelalgia. Salicylates and treatment of the underlying polycythemia were able to eliminate the skin lesions but not entirely suppress the subjective discomfort.