Gaëtan Vanstraelen

Translocation (16;17)(Q22;P13) Is a Recurrent Anomaly of Aneurysmal Bone Cysts

Recently, Panoutsakopoulos et al. (1999) reported 2 cases of aneurysmal bone cysts with a recurrent (16;17)(q22;p13) translocation. We present here two additional cases harboring the same translocation as well as additional chromosomal changes.

Darbepoetin-alfa and intravenous iron administration after autologous hematopoietic stem cell transplantation : A prospective multicenter randomized trial

We conducted a randomized study analyzing the impact of darbepoetin alfa (DA) administration with or without intravenous (i.v.) iron on erythroid recovery after autologous hematopoietic cell transplantation (HCT). Patients were randomized between no DA (Arm 1), DA 300 μg every 2 weeks starting on Day 28 after HCT (Arm 2), or DA plus i.v. iron 200 mg on Days 28, 42, and 56 (Arm 3). The proportion achieving complete hemoglobin (Hb) response within 18 weeks (primary end point) was 21% in Arm 1 (n = 24), 79% in Arm 2 (n = 25), and 100% in Arm 3 (n = 23; P < 0.0001). Erythropoietic response was shown to be significantly higher in Arm 3 (n = 46) than in Arm 2 (n = 50; P = 0.008), resulting in lower DA use, reduced drug costs, and improved quality of life scores, but the effect on transfusions was not significant. In multivariate analysis, DA administration (P < 0.0001), i.v. iron administration (P = 0.0010), high baseline Hb (P < 0.0001), and low baseline creatinine (P = 0.0458) were independently associated with faster achievement of complete Hb response. In conclusion, DA is highly effective to ensure full erythroid reconstitution after autologous HCT when started on Day 28 post‐transplant. I.v. iron sucrose further improves erythroid recovery. Am. J. Hematol. 88:990–996, 2013.

Erythropoietin therapy after allogeneic hematopoietic cell transplantation: a prospective, randomized trial

We conducted a prospective randomized trial to assess hemoglobin (Hb) response to recombinant human erythropoietin (rhEPO) therapy after hematopoietic cell transplantation (HCT). Patients (N = 131) were randomized (1:1) between no treatment (control arm) or erythropoietin at 500 U/kg per week (EPO arm). Patients were also stratified into 3 cohorts: patients undergoing myeloablative HCT with rhEPO to start on day (D)28, patients given nonmyeloablative HCT (NMHCT) with rhEPO to start on D28, and patients also given NMHCT but with rhEPO to start on D0. The proportion of complete correctors (ie, Hb ≥13 g/dL) before D126 posttransplant was 8.1% in the control arm (median not reached) and 63.1% in the EPO arm (median, 90 days) (P < .001). Hb levels were higher and transfusion requirements decreased (P < .001) in the EPO arm, but not during the first month in the nonmyeloablative cohort starting rhEPO on D0. There was no difference in rates of thromboembolic events or other complications between the 2 arms. This is the first randomized trial to demonstrate that rhEPO therapy hastens erythroid recovery and decreases transfusion requirements when started one month after allogeneic HCT. There was no benefit to start rhEPO earlier after NMHCT.

Non-myeloablative transplantation with CD8-depleted or unmanipulated peripheral blood stem cells: a phase II randomized trial.

Non-myeloablative transplantation with CD8-depleted or unmanipulated peripheral blood stem cells: a phase II randomized trial

Transfusions after nonmyeloablative or reduced-intensity conditioning regimens

Allogeneic hematopoietic cell transplantation (HCT) following reduced-intensity conditioning (RIC) or nonmyeloablative conditioning has been an effective treatment for many patients with hematological malignancies, as well as for selected patients with solid cancers or inherited blood disorders. A number of different RIC or nonmyeloablative conditioning regimens have been explored. The separation of what constitutes a nonmyeloablative versus a RIC regimen is somewhat arbitrary (Table 1), although Giralt proposed some criteria for nonmyeloablative conditioning that included (1) no eradication of host hematopoiesis, (2) prompt hematologic recovery (o4 weeks) without transplant and (3) presence of mixed chimerism upon engraftment. Similarly, the distinction between RIC and myeloablative conditioning has been discussed; the criteria proposed by Giralt included p5 Gy total body irradiation (TBI), p9 mg/kg busulfan dose, p140 mg/m melphalan dose and p10 mg/kg thiothepa dose. RIC regimens have combined modest doses of fludarabine (used mainly for its immunosuppressive activity) with consequent (but nonmyeloablative) doses of alkylating agents such as melphalan (140 mg/m) or busulfan (4–8 mg/kg), given to produce major anti-tumor effects with the hope of controlling the malignancy before the occurrence of the immune-mediated graft-versus-tumor effects. In contrast, nonmyeloablative conditioning has used potent immunosuppressive regimens to overcome host-versus-graft reactions (graft rejection), allowing engraftment of donor hematopoietic and immune cells. Thus, following nonmyeloablative conditioning, eradication of both host hematopoiesis and tumor cells is mediated nearly exclusively by immune-mediated graft-versushost effects. The degree of myelosuppression induced by RIC or nonmyeloablative regimens has varied from one regimen to another, those including intermediate doses of either busulfan (8 mg/kg) or melphalan (140 mg/m) being the most myelosuppressive, whereas the one using low-dose TBI (2 Gy) with or without fludarabine being the least myelosuppressive (Figure 1 and Table 1). We compared erythropoietic activity in patients given allogeneic grafts after either myeloablative (n1⁄4 57) or nonmyeloablative (n1⁄4 54) conditioning (Figure 2). Nonmyeloablative conditioning consisted of 2 Gy TBI (n1⁄4 20), 2 Gy TBI plus fludarabine (90 mg/m, n1⁄4 29), or cyclophosphamide (3 g/m) plus fludarabine (90 mg/m, n1⁄4 5). Erythropoietic activity was quantified by assessing the levels of the serum soluble transferrin receptor (sTfR, a quantitative marker of total erythropoietic activity). After myeloablative conditioning, erythropoietic activity decreased sharply and remained abnormally low the first month after HCT. In contrast, erythropoietic activity remained consistently above the lower limit of normal values after nonmyeloablative conditioning, demonstrating that the regimens were indeed mildly myelosuppressive. In this article, we first describe what is currently known about red blood cell (RBC) and platelet transfusion requirements after RIC or nonmyeloablative conditioning, and then review which factors are associated with increased transfusion requirements. In the second part of the review, we discuss the potential role of hematopoietic growth factors such as erythropoietin (Epo) or granulocyte colony-stimulating factor (G-CSF) after nonmyeloablative or RIC HCT.

Results from the Belgian mantle cell lymphoma registry.

Introduction: Mantle cell lymphoma is a B-cell non-Hodgkin’s lymphoma characterized by a t(11;14), resulting in overexpression of cyclin D1. Conventional chemotherapy obtains frequent (but short) remissions, leading to a poor median overall survival (OS) of 3–5 years. To obtain more information about the prevalence and current treatment of Mantle cell lymphoma (MCL) in Belgium, we collected data in a Belgian registry of MCL. Materials and methods: All Belgian MCL patients, t(11;14) and/or cyclin D1 positive, seen in hematology departments over a one-year period (April 2013–March 2014) were included. Data about patient characteristics, histology, treatment lines, and response were compiled and retrospectively analyzed. Results: Four hundred and four patients were included with a median age at diagnosis of 64 years (range 23–96 years) and a male predominance (72%). For 2013, we calculated a prevalence of at least 36.2 per million and an incidence of at least 7.0 per million in the Belgian population. Characteristics at diagnosis involved lymphadenopathy (82%), splenomegaly (44%), B-symptoms (39%), and hepatomegaly (10%). Bone marrow invasion was present at diagnosis in 77%. Stage at diagnosis was advanced in the majority of cases. The median number of treatment lines was 1. Type of first line treatment included a combination of anthracyclin and cytarabine-based regimen (34%), anthracyclin (39%), and other. Rituximab was used in 88% of first line treatments. In 44% first line treatment was followed by autologous stem cell transplantation. Conclusion: The analysis of this Belgian MCL registry provides insight in the epidemiology, demographics, and current treatment of our Belgian MCL population.