Artit Ungkanont

Successful treatment of refractory autoimmune haemolytic anaemia in a post-unrelated bone marrow transplant paediatric patient with rituximab.

Here, we report a case of paediatric β-thalassaemia major patient who underwent unrelated T cell-non- depleted bone marrow transplantation and developed a complication of autoimmune haemolytic anaemia (AIHA) refractory to corticosteroid and intravenous immunoglobulin therapy. After this child received two doses (375 mg/m2/dose) of rituximab (anti-CD20 monoclonal antibody), his AIHA was resolved.

Hematopoietic stem cell transplantation for homozygous β-thalassemia and β-thalassemia/hemoglobin E patients from haploidentical donors

Thalassemia-free survival after allogeneic stem cell transplantation (SCT) is about 80–90% with either matched-related or -unrelated donors. We explored the use of a mismatched-related (‘haplo- ’) donor. All patients received two courses of pretransplant immunosuppressive therapy (PTIS) with fludarabine (Flu) and dexamethasone (Dxm). After two courses of PTIS, a conditioning regimen of rabbit antithymocyte globulin, Flu and IV busulfan (Bu) was given followed by T-cell-replete peripheral blood progenitor cells. GvHD prophylaxis consisted of cyclophosphamide (Cy) on days SCT +3 and +4 (post-Cy), and on day SCT +5 tacrolimus or sirolimus was started together with a short course of mycophenolate mofetil. Thirty-one patients underwent haplo-SCT. Their median age was 10 years (range, 2–20 years). Twenty-nine patients engrafted with 100% donor chimerism. Two patients suffered primary graft failure. Median time to neutrophil engraftment was 14 days (range, 11–18 days). Five patients developed mild to moderate, reversible veno-occlusive disease, while nine patients developed acute GvHD grade II. Only five patients developed limited-chronic GvHD. Projected overall and event-free survival rates at 2 years are 95% and 94%, respectively. The median follow up time is 12 months (range, 7–33 months).

Indices of Iron status in continuous ambulatory peritoneal dialysis patients

Data for iron-status indices in continuous ambulatory peritoneal dialysis patients are limited. The reliability of commonly used indices for the diagnosis of iron-deficiency anemia in peritoneal dialysis patients is still unknown. To study diagnostic values of iron-status indices, including serum ferritin, transferrin saturation, reticulocyte hemoglobin content, and bone marrow-stainable iron, 21 stable anemic peritoneal dialysis patients who have been treated with erythropoietin and oral iron supplementation for more than 3 months were enrolled in this study. The mean age was 51.4 +/- 2.9 years; dialysis duration, 28.7 +/- 5.1 months; initial hemoglobin, 8.4 +/- 0.2 g/dL; erythropoietin dosage, 71 +/- 2 micro/kg/wk; serum albumin, 3.5 +/- 0.1 g/dL; intact parathyroid hormone (PTH), 233 +/- 44 ng/mL; serum ferritin, 643 +/- 135 ng/mL; transferrin saturation, 33.93% +/- 3.9%; and reticulocyte hemoglobin content, 31.6 +/- 4 pg. Bone marrow aspiration was performed in all patients to determine marrow iron content and exclude hematological disorders. All patients were treated with 1, 000 mg of intravenous ferric saccharate infusion in two divided doses more than 1 week apart. Patients who responded to the iron infusion within 3 months by increasing serum hemoglobin of greater than 1 gm/dL more than baseline were defined as being functional iron deficient before the intravenous iron infusion. Serum ferritin, transferrin saturation, and reticulocyte hemoglobin content were followed serially after iron infusion. Fifteen patients (71.4%) responded to the iron administration, indicating iron deficiency. Nine of 13 (69%) patients with the presence of bone marrow-stainable iron still responded to intravenous iron supplementation, suggesting functional iron deficiency. Absence of bone marrow-stainable iron was not a sensitive marker for the diagnosis of iron deficiency, 25% sensitivity. No single value of iron-status indices that can definitely exclude iron-deficiency anemia in peritoneal dialysis patients was found. Therefore, failure to increase hemoglobin concentration after intravenous iron administration should be shown before excluding iron-deficiency anemia as a cause of poor erythropoietic response to erythropoietin therapy.

Treatment outcome of thalidomide based regimens in newly diagnosed and relapsed/refractory non-transplant multiple myeloma patients: a single center experience from Thailand.

BackgroundThalidomide based regimen is an effective and well tolerated therapy in multiple myeloma (MM) patients, however, there were a small number of studies written about the results of thalidomide therapy in non-transplant MM patients. We therefore conducted a retrospective study of 42 consecutive patients with newly diagnosed and relapsed/refractory MM treated with thalidomide- based induction regimens followed by thalidomide maintenance therapy.ResultsInduction regimens with thalidomide and dexamethasone, and the oral combination of melphalan, prednisolone and thalidomide were administrated in 22 and 16 patients, respectively. The remaining 4 patients received other thalidomide- containing regimens. Twenty-nine patients received thalidomide as a salvage regimen. Twenty-three out of 26 patients achieving complete remission (CR) and very good partial remission (VGPR) received thalidomide maintenance. Of the 41 evaluable patients, median time of treatment was 21 months (3- 45 months), ORR was 92.7% with a 63.4% CR/VGPR. With a median follow up of 23 months, 3-year- PFS and 3-year-OS were 58.6 and 72.6%, respectively. Median time to progression was 42 months. While 3-year-PFS and 3-year-OS in non-transplant patients receiving thalidomide maintenance therapy were 67 and 80%, respectively.ConclusionsProlonged thalidomide therapy enhanced survival rate and less frequently developed serious toxicity in non-transplant multiple myeloma patients.

Outcome of transplantation with unrelated donor bone marrow in children with severe thalassaemia

Summary:We conducted a study of unrelated donor bone marrow transplantation (BMT) in 11 children with severe thalassaemia. The conditioning regimen consisted of busulphan, cyclophosphamide and antilymphocyte globulin. All received T-cell nondepleted bone marrow. The median marrow-nucleated cell dose was 4.9 × 108 /kg (range; 3.5−8.0 × 108 /kg). Median time of granulocyte recovery was 16 days (range; 13–21 days), and of platelet recovery was 39 days (range; 14–196). Grade 2–4 acute graft-versus-host disease (GVHD) developed in six patients (54%), and grade 3–4 in one patient (9%). Three (27%) of 11 evaluable patients had chronic GVHD (limited stage). All 11 patients are alive without thalassaemia after a median follow-up time of 397 days (range; 171–814 days). This study lends support to consideration of unrelated donor BMT as an acceptable therapy to cure severe thalassaemia especially in patients who are young and do not yet show irreversible severe complications of iron overload.

Outcomes of Thalassemia Patients Undergoing Hematopoietic Stem Cell Transplantation by Using a Standard Myeloablative versus a Novel Reduced-Toxicity Conditioning Regimen According to a New Risk Stratification

Improving outcomes among class 3 thalassemia patients receiving allogeneic hematopoietic stem cell transplantations (HSCT) remains a challenge. Before HSCT, patients who were ≥ 7 years old and had a liver size ≥ 5 cm constitute what the Center for International Blood and Marrow Transplant Research defined as a very high-risk subset of a conventional high-risk class 3 group (here referred to as class 3 HR). We performed HSCT in 98 patients with related and unrelated donor stem cells. Seventy-six of the patients with age < 10 years received the more conventional myeloablative conditioning (MAC) regimen (cyclophosphamide, busulfan, ± fludarabine); the remaining 22 patients with age ≥ 10 years and hepatomegaly (class 3 HR), and in several instances additional comorbidity problems, underwent HSCT with a novel reduced-toxicity conditioning (RTC) regimen (fludarabine and busulfan). We then compared the outcomes between these 2 groups (MAC versus RTC). Event-free survival (86% versus 90%) and overall survival (95% versus 90%) were not significantly different between the respective groups; however, there was a higher incidence of serious treatment-related complications in the MAC group, and although we experienced 6 graft failures in the MAC group (8%), there were none in the RTC group. Based on these results, we suggest that (1) class 3 HR thalassemia patients can safely receive HSCT with our novel RTC regimen and achieve the same excellent outcome as low/standard-risk thalassemia patients who received the standard MAC regimen, and further, (2) that this novel RTC approach should be tested in the low/standard-risk patient population.

Therapy-related myelodysplastic syndrome/acute myeloid leukemia following fludarabine therapy for non-Hodgkin lymphoma and chronic lymphocytic leukemia in Thai patients

Therapy related myelodysplastic syndrome (t-MDS) and secondary acute myeloid leukemia (AML) are seriously late complications of the use of alkylating agents, topoisomerase II inhibitors, and other chemotherapies. Deoxyribonucleic acid (DNA) damage that leads to chromosomal deletions or balanced translocations partly cause t-MDS. Deletions of chromosomes 5 and 7 are also commonly found in alkylator-associated MDS/AML. Over the last half decade, fludarabine has been widely used as frontline therapy for indolent B-cell lymphomas and chronic lymphocytic leukemia (CLL). The incidence of t-MDS/AML following fludarabine-based therapies is 0.5%, 3.5%, 9%, and 2% of patients receiving treatment with fludarabine alone, fludarabine plus chlorambucil, fludarabine combined with cyclophosphamide, and the combination of rituximab, fludarabine, and cyclophosphamide, respectively [1,2]. Nevertheless, the risk factor for fludarabine-induced t-MDS/AML has not been established. We therefore performed a retrospective study to analyze the predicting factors for t-MDS/AML in patients with B-cell lymphomas and CLL treated with fludarabinebased therapy. Thirty-eight patients with B-cell lymphomas and CLL receiving fludarabine-based therapy at Ramathibodi Hospital between January 2003 and December 2008 were included in the analysis. This included all patients with CLL treated with fludarabine at our hospital, with the following exceptions: patients who died within 1 year after fludarabine therapy from non-MDS causes, or patients who received treatment with stem cell transplant, immunoradiotherapy, or a salvage regimen, such as ICE (ifosfamide, carboplatin, etoposide), ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin), IMVP-16 (ifosfamide, methotrexate, etoposide), and hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone), were excluded. Thirty-eight patients were treated with fludarabine (F) 30 mg/m/day intravenously (i.v.) for 3 consecutive days, and cyclophosphamide was included for 33 patients receiving the FC regimen. The doses of cyclophosphamide were as follows: cyclophosphamide 600 mg/m/day i.v. on day 1 (nine patients), or cyclophosphamide 200 mg/m/day i.v. for 3 consecutive days (24 patients). Rituximab 500 mg/day

Transcoronary Infusion of Bone Marrow Derived Multipotent Stem Cells to Preserve Left Ventricular Geometry and Function After Myocardial Infarction

Myocardial damage after myocardial infarction (MI) was deemed irreversible after late reperfusion. Administration of multipotent stem cell (MSC) into such infarct may regenerate the myocardium and capillary network.

The use of hematocrit level for predicting the efficiency of peripheral blood CD34(+) cell collection after G-CSF Mobilization in Healthy Donors.

Recently, peripheral blood stem cell (PBSC) has been widely used and replaced bone marrow (BM) as the stem cell source in allogeneic hematopoietic stem cell transplantation (HSCT) because of a more rapid engraftment, easier accessibility, and lower risk of donor complications. We, therefore, report the predicting factors for the high PBSC harvest yields in 50 healthy donors. Among the 50 donors, median collected CD34+ cell number was 4.6 × 106/kg (1.5–16.3 × 106/kg). Number of circulating CD34+ cells and hematocrit (HCT) level increased parallelly whereas peripheral CD34+ cell numbers were decreased with increasing donor age. In univariate analysis, HCT level≥ 35.5% at the time of PBSC collection was significantly associated with high PBSC number (≥ 5.0 × 106 cells/kg) and donor aged <30 years was significantly associated with collected CD34+ cells ≥ 6.0 × 106/kg, P = 0.03. HCT level ≥35.5% was an independent parameter for high WBC count (≥50 × 109/L), P < 0.05. None of donor who had both HCT < 35.5% and WBC < 50 × 109/L had circulating CD34+ cells ≥ 5.0 × 106/kg. Platelet count ≥ 200 × 109/L was found significantly in donors with WBC ≥ 40 × 109/L (P = 0.03) and HCT ≥ 35.5%, P < 0.05. Collected PBSC number tended to be higher in our donors with high levels of HCT, WBC, and platelet. We also found that HCT and platelet levels in our donors decreased after receiving G‐CSF administration compared with the initial complete blood counts (CBC) results. We, therefore, concluded that HCT level at the time of initiation leukapheresis was an important predictor for PBSC collection yields. J. Clin. Apheresis 30:329–334, 2015.

Nonmyeloablative stem cell transplantation with a haploidentical donor in a class 3 lucarelli severe thalassemia patient

Nonmyeloablative stem cell transplantation with a haploidentical donor in a class 3 lucarelli severe thalassemia patient