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 × 10(6/) kg (1.5-16.3 × 10(6) /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 × 10(6) cells/kg) and donor aged <30 years was significantly associated with collected CD34+ cells ≥ 6.0 × 10(6) /kg, P = 0.03. HCT level ≥35.5% was an independent parameter for high WBC count (≥50 × 10(9) /L), P < 0.05. None of donor who had both HCT < 35.5% and WBC < 50 × 10(9) /L had circulating CD34+ cells ≥ 5.0 × 10(6) /kg. Platelet count ≥ 200 × 10(9) /L was found significantly in donors with WBC ≥ 40 × 10(9) /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.

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.

Pretransplant immunosuppression followed by reduced-toxicity conditioning and stem cell transplantation in high-risk thalassemia: a safe approach to disease control.

Patients with class 3 thalassemia with high-risk features for adverse events after high-dose chemotherapy with hematopoietic stem cell transplantation (HSCT) are difficult to treat, tending to either suffer serious toxicity or fail to establish stable graft function. We performed HSCT in 18 such patients age ≥7 years and hepatomegaly using a novel approach with pretransplant immunosuppression followed by a myeloablative reduced-toxicity conditioning regimen (fludarabine and i.v. busulfan [Flu-IV Bu]) and then HSCT. The median patient age was 14 years (range, 10 to 18 years). Before the Flu-IV Bu + antithymocyte globulin conditioning regimen, all patients received 1 to 2 cycles of pretransplant immunosuppression with fludarabine and dexamethasone. Thirteen patients received a related donor graft, and 5 received an unrelated donor graft. An initial prompt engraftment of donor cells with full donor chimerism was observed in all 18 patients, but 2 patients developed secondary mixed chimerism that necessitated withdrawal of immunosuppression to achieve full donor chimerism. Two patients (11%) had acute grade III-IV graft-versus-host disease, and 5 patients had limited chronic graft-versus-host disease. The only treatment-related mortality was from infection, and with a median follow-up of 42 months (range, 4 to 75), the 5-year overall survival and thalassemia-free survival were 89%. We conclude that this novel sequential immunoablative pretransplantation conditioning program is safe and effective for patients with high-risk class 3 thalassemia exhibiting additional comorbidities.

Effectiveness and Safety of Direct Oral Anticoagulants in Thai Patients with Atrial Fibrillation: A Real-World Retrospective Cohort Study.

BACKGROUND: Direct oral anticoagulants (DOACs) are commonly used to prevent stroke and systemic embolism in patients with atrial fibrillation (AF). However, studies into their effectiveness and safety in the Thai population have so far been limited. OBJECTIVES: To study the effectiveness and safety of warfarin and DOACs among Thai AF patients. METHODS: A retrospective cohort study was conducted on AF patients at Ramathibodi Hospital from 2013 to 2018. All patients were followed for at least 1 year. Relevant clinical information was collected and compared between AF patient groups receiving warfarin, dabigatran, rivaroxaban, and apixaban. The primary outcome was a composite of major bleeding, ischemic stroke, and systemic thromboembolism. The secondary outcomes were all-cause mortality and disease-specific mortality caused by major bleeding, ischemic stroke, and systemic thromboembolism. RESULTS: A total of 1680 AF patients were enrolled in the study (warfarin 1193, apixaban 140, dabigatran 193, rivaroxaban 114). The estimated incidence of composite outcome was 16% [95% CI, 14-18%] and 12.4% [95% CI, 9.4-15.3%] in the warfarin and DOAC group, respectively, given a number needed to treat of 28 [95% CI, 3-52]. Compared with warfarin, DOACs were associated with both lower rate of all-cause mortality (4.9% [22/447] vs 8% [98/1193]) and lower disease-specific mortality (0.4% [2/447] and 1% [12/1193]). CONCLUSIONS: This study suggests DOACs were associated with a lower risk of major bleeding, ischemic stroke, and systemic thromboembolism compared to warfarin in Thai patients with AF. Patients receiving DOAC also had a lower rate of all-cause mortality and disease-specific mortality.

Trends in disease indications for hematopoietic stem cell transplantation in the Asia-Pacific region: A report of the Activity Survey 2017 from APBMT.

The Asia-Pacific Blood and Marrow Transplantation Group (APBMT) has been conducting annual surveys on the activity of hematopoietic stem cell transplants since 2007. The APBMT Data Center collected the following data in 2017. A total of 21,504 transplants were registered from 733 transplant centers of 20 countries/regions in the Asia-Pacific (AP) region. Five countries/regions comprised 89.4% of all transplants - China (6,979), Japan (5,794), South Korea (2,626), India (2,034), and Australia (1,789). The number of centers in these five countries/regions also comprised 88.9% of all centers: Japan (373), China (123), India (66), Australia (45), and South Korea (44). The overall ratio between autologous and allogeneic transplants was 37.0% and 63.0%, respectively, but the ratios varied significantly among countries/regions. Autologous transplants have surpassed allogeneic transplants in Thailand, Australia, Vietnam, New Zealand, Singapore, and Iran. In contrast, the proportion of allogeneic transplants comprised over 70% of all transplants in Pakistan, China, and Hong Kong. These ratios were compared by the Data Center among countries/regions that performed more than 50 transplants. The proportion of related and unrelated transplants also differed among countries/regions. The number of unrelated transplants was more than related ones in Japan (2,551 vs. 1,202) and Australia (329 vs. 291), whereas more than 80% of all transplants were related transplants in Malaysia (90.9%), India (89.5%), Iran (87.2%), Vietnam (85.7%), China (80.9%), and Thailand (80.6%). All transplant activities were related transplants in Pakistan, the Philippines, Myanmar, and Nepal, and no allogeneic transplants were performed in Bangladesh and Mongolia. Regarding the indications for transplants, acute myeloid leukemia (AML) was the most common disease for allogeneic transplant (4,759, 35.1% of allogeneic transplants), while plasma cell disorder (PCD) was the most common disease for autologous transplant (3,701, 27.3% of all autologous transplants). Furthermore, the number of transplants for hemoglobinopathy has steeply increased in this region compared with the rest of disease indications (677, 3.1% of all transplants). APBMT covers a broad area globally, including countries/regions with diverse disease distribution, development of HSCT programs, population, and economic power. Consistent and continuous activity surveys considering those elements in each country/region revealed the HSCT field's diverse characteristics and background factors in this region.

Treatment Outcomes and Clinical Relevance in Patients with Double Expressor DLBCL.

BACKGROUND: Double-expressor lymphoma (DEL) was found to account for 20-30% of DLBCL. We conducted this study to analyze the survival, the clinical presentation, and the factors associated with treatment outcomes in DEL-DLBCL. METHODS: A retrospective study of 291 patients diagnosed with DLBCL during January 2015 - December 2018 was conducted. RESULTS: Of the 291 patients, the median age was 63 years, germinal center B cell-like DLBCL (GCB) and non-GCB subtypes were found in 32% and 68%, respectively. DEL was found in 46% of 264 patients with available immunohistochemistry staining for MYC protein. Patients with DEL was significantly more common in elderly patients (p= 0.017) and non-GCB subtype (p= 0.006). High serum lactate dehydrogenase (LDH) levels and high Ki-67 index were significantly found in DEL patients than non-DEL patients (p= 0.024 and p= 0.04, respectively). The 3y-OS rate was shorter in the DEL group than in the non-DEL group, 58.7% versus 78.9% (p=0.026), whereas no significant difference in 3y-DFS was identified between these groups (58.4% versus 67.7%, p= 0.343). Independent factors affecting OS and DFS in DEL patients were ECOG 3-4, high LDH levels, extranodal involvement> 1 site, high IPI, and stage III-IV in univariate analysis. CONCLUSIONS: High incidence of DEL was observed in this study, especially in patients aged 60 years or older and non-GCB subtype. Patients with DEL showed dismal DFS and OS.

The 2016 APBMT Activity Survey Report: Trends in haploidentical and cord blood transplantation in the Asia-Pacific region.

This report describes the results of the Asia-Pacific Blood and Marrow Transplantation Group (APBMT) Activity Survey 2016, focusing on the trends of haploidentical and cord blood (CB) transplants in the Asia-Pacific region. Mongolia and Nepal submitted their first activity data in this survey, and the number of countries/regions participating in the activity survey grew to 20. The annual number of transplants exceeded 20,000 for the first time in 2016, and the total number of centers increased to 686. About 87.9% of all hematopoietic stem cell transplantations (HSCTs) were performed in China, Japan, Korea, India, and Australia with China performing the highest number. Beginning with the 2016 survey, APBMT modified the survey forms and initiated the collection of the exact number of haploidentical transplants. The total number of such transplants was 3,871, and 66.0% of those were performed in China. Meanwhile, cord blood transplants in this region remained high (1,612), and 81.8% of them (1,319) were performed in Japan. The number of facilities and transplants, the ratio of haploidentical transplants to related transplants, the ratio of CB transplants to unrelated transplants, and proportions of haploidentical and CB transplants per capita significantly differed among countries/regions in the Asia-Pacific region. Data collection and analysis revealed the transition and diversity of transplants in this region. This report also shows a dramatic increase in haploidentical transplants as seen in other parts of the world, while revealing uniquely that the activity of cord blood transplant remains high in this region.

Long-term outcomes of de novo acute myeloid leukemia in Thai patients.

BACKGROUND: Acute myeloid leukemia (AML) is the heterogeneous disease. As per previous reports, there are some differences in clinical features and cytogenetic biomarkers of AML among different ethnic backgrounds. Therefore, we conducted a retrospective study to analyze clinical outcomes and predictive factors of Thai AML patients receiving chemotherapy treatment. MATERIAL AND METHOD: The authors performed a retrospective analysis of 106 adults with newly diagnosed de novo AML at Ramathibodi Hospital between 2003 and 2007. Of 101 patients with non- M3 subtype, the patients received induction and consolidation chemotherapy with anthracyclin plus cytarabine based regimens (3 + 7). All patients achieving complete remission (CR) were treated with intensive chemotherapy using intermediate dose cytarabine plus anthracyclin based protocol. All patients with M3 subtype, the induction chemotherapy consisted of a combination of all-trans retinoic acid (ATRA) and anthracyclin. All patients achieving complete remission (CR) were treated with three courses of mitoxantrone as consolidation chemotherapy, followed by maintenance chemotherapy with methotrexate, etoposide and ATRA. RESULTS: Of the 106 patients, median age was 43.5 years (15-73 years) and 19 (17.9%) were older than 60 years. Fifty-six patients (52.8%) were female. Common subtypes were M4 (28.3%), M1 (26.4%) and M2 (20.8%). Of the 95 patients who were performed with cytogenetic analysis, 55 (58%) had abnormal karyotype. AML with recurrent cytogenetic translocations, complex chromosome, trisomy 8, polyploidy, del 5q and del 7q were found in 16.8, 6.3, 5.3, 5.3, 2.1 and 3.2%, respectively. Most patients (70.5%) had intermediate-risk cytogenesis. Eighty patients (75.5%) were treated with idarubicin and cytarabine induction regimen. Of the 96 evaluable patients, 60 (62.5%) achieved complete remission (CR), 38 (39.6%) with the first course of chemotherapy. Median time to CR was 54 days (25-168 days). The CR rate was 78.6% for the good-risk cytogenetic group, 67.2% for the intermediate- risk cytogenetic group, and 37.5% for the poor-risk cytogenetic group. Median follow-up time was 10.4 months, 5-year-DFS and 5-year-OS were 41 and 22.2%, respectively. Patients with poor-risk cytogenetic factors had significantly lower CR rate (p = 0.021). The CR status significantly predicted OS (p < 0.001). CONCLUSION: The overall complete remission rate of Thai AML patients is in 60%. Only a small proportion of the presented patients have long-term DFS and OS, the significant factor for predicting survival of Thai AML patients is the complete remission status. Poor-risk cytogenetic factors are associated with poor treatment outcomes.

Cytogenetics and FLT3-ITD mutation predict clinical outcomes in non transplant patients with acute myeloid leukemia.

BACKGROUND: Cytogenetic abnormalities and mutated genes indicate the role of consolidation therapy with hematopoietic stem cell transplantation (HSCT) or chemotherapy in acute myeloid leukemia (AML). In this study, we conducted a retrospective study in adult AML patients with newly diagnosed with de novo AML who did not undergo HSCT, to study long term relapse free survival (RFS) and overall survival (OS) after consolidation chemotherapy. METHODS: We recruited 141 consecutive AML patients during January 2010-June 2017, the patients received induction chemotherapy with standard dose Ara-C and Idarubicin (7 + 3 or 5 + 2 regimen) followed by intermediate (IDAC) or high dose Ara-c (HiDAC) consolidation therapy. RESULTS: Normal karyotype, complex, favorable, intermediate and adverse chromosomal aberrations were found in 59%, 16%, 5%, 14% and 6%, respectively. Mutated NPM1, FLT3-ITD and CEBPA genes in CN-AML were seen in 33%, 18% and 19%, respectively. A 5 year follow up, 5y-RFS was 16% and 5y-OS was 14% in the whole study population. 5y-RFS and 5y-OS in patients completed 4 cycles of consolidation therapy were 25% and 40%, respectively. Adverse cytogenetic risk and mutated FLT3-ITD were significantly associated with poor RFS (9 and 15 months, respectively) and OS (14 and 16 months, respectively), whereas patients with mutant NPM1 had favorable outcomes (RFS/OS = 51/63 months). Patients receiving 4 cycles of consolidation therapy had significantly impacts on median RFS and OS compared with those treated with 1 or 2 cycles; 15 versus 11 months (p = 0.006) and 31 versus 15 months (p < 0.001), respectively. CONCLUSIONS: Cytogenetic and mutation tests for FLT3-ITD, NPM1 and CEBPA genes were meaningful for predicting outcomes in adult AML patients. Adverse cytogenetic abnormalities and FLT3-ITD mutation showed dismal RFS and OS.

Treatment outcome and prognostic factors in PCNSL.

OBJECTIVES: Standard treatment with a thiotepa-based regimen in countries with a limited resource is less feasible. Aims of the study were to evaluate the treatment outcome, and identify the prognostic factors in patients with primary central nervous system lymphoma (PCNSL). METHODS: We conducted a retrospective study of 43 patients diagnosed with PCNSL, DLBCL subtype, who were treated with either HDMTX-based regimen, whole brain radiotherapy (WBRT), or both between 2010 and 2017. RESULTS: There were 43 patients with a median age of 65 years (range 34-89 years). Protein expression of CD10, Bcl6, MUM1, Bcl2 and MYC were found in 19, 86, 91, 91 and 23%, respectively. Both germinal center B cell (GCB) and double-expressor (MYC+/Bcl2+) lymphomas were found in 21%. Multiple brain lesions and maximum tumor diameter (MTD) ≥5 cm were seen in 27 and 10 patients, respectively. Chemotherapy combined with WBRT, chemotherapy and WBRT were given to 20, 14 and 9 patients, respectively. Overall complete remission (CR) rate was 55.8%. Those receiving a combined-modality therapy had a higher CR rate than those treated with either chemotherapy (75% versus 36%, p = 0.036) or WBRT (75% versus 44%, p = 0.109). Median follow-up time was 17 months, and a 7-year overall survival (OS) was 40%. Features associated with a prolonged OS were an ECOG score ≤ 2 (p = 0.001), multiple brain lesions (p = 0.010), multiple area of brain involvement (p = 0.023), MTD < 5 cm (p = 0.004), GCB subtype (p = 0.003) and positive CD10 staining (p = 0.007). Expression of Bcl2 protein was associated with a significantly worse OS in the non-GCB DLBCL patients. DISCUSSION: The factors affecting treatment outcomes in PCNSL were cell of origin of DLBCL, lesion characteristics, patients' status and treatment regimen.

A prophylactic approach for bone marrow transplantation from a hepatitis B surface antigen-positive donor.

It has been accepted that bone marrow transplantation (BMT) is the only curative therapeutic option for certain hematologic malignancies. The southeast Asia region is an endemic area of hepatitis B virus (HBV) infection; thus, BMT using a hepatitis B surface antigen (HBsAg)-positive donor is occasionally unavoidable. Organ transplantation using a HBsAg-positive donor can lead to post-transplantation de novo HBV infection and severe HBV-related hepatitis if no effective prophylactic measures are taken prior to and after transplantation. In this report, a four-level approach was designed for a patient with chronic myeloid leukemia, beginning with a booster HBV vaccination before performing BMT with a HBsAg-positive donor. Prior to BMT, the HBV viral load of the donor was reduced to an undetectable level by antiviral therapy. After BMT, hepatitis B immunoglobulin was administered intramuscularly for 1 wk together with a long-term antiviral drug, lamivudine. One year after discontinuation of lamivudine, the patient is still free of HBV infection.

Bone marrow derived mesenchymal stem cells from chronic myeloid leukemia t(9;22) patients are devoid of Philadelphia chromosome and support cord blood stem cell expansion.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells. It is characterized at cytogenetic level by the Philadelphia (Ph) chromosome and at the molecular level by the BCR/ABL gene rearrangement. Bone marrow derived mesenchymal stem cells (MSCs) are also pluripotent stem cells that can differentiate into several mesenchymal tissues. To date, no study has been performed to characterize whether MSCs from CML harbor the abnormal Ph chromosome similar to CML bone marrow cells. We isolated and characterized MSCs from diagnostic marrow samples (n=11) and showed that MSCs can be readily isolated from CML marrow and exhibit major expansion potential as well as intact osteogenic differentiation ability. Moreover, they do not harbor the Ph chromosome confirmed by fluorescence in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR). Thus, we demonstrated that CML marrow is an abundant source of MSCs appearing through both FISH and RT-PCR not to be involved by the malignant process of CML. Furthermore, these MSCs from a CML patient could support in vitro cord blood expansion as those MSCs from a normal donor. Since MSCs are able to support engraftment of hematopoietic stem cells in stem cell transplantation (SCT) as well as suppress alloreactive T cells causing graft-versus-host disease, this current report thus provides evidence that in a SCT setting of CML patients, autologous MSCs could be a source of stem cell support in future cell therapy applications.

Evidence-based medicine in clinical curriculum.

INTRODUCTION: The teaching of evidence-based medicine (EBM) has now been incorporated as an integral part of medical curriculum at the Faculty of Medicine, Ramathibodi Hospital but there is little research into the effectiveness of the course. The purpose of this report is to evaluate the EBM skills of medical students and competency of the faculty member. MATERIALS AND METHODS: The EBM course was created by the EBM Working Group at the Faculty of Medicine, Ramathibodi Hospital for 3rd- to 6th-year medical students. The principles of EBM, clinical epidemiology and biostatistics were gradually instilled during the 4 years of medical school. Information technology infrastructure was also provided to facilitate critical appraisal skills. At the end of the Community Medicine clerkship, students anonymously evaluated aspects of the course regarding their EBM skills and faculty member competency with Likert scale questions. RESULTS: Medical students generally gave high evaluations to all aspects of the EBM course taught in the Community Medicine Department. For each of the evaluation questions, the means were higher for faculty member competency. CONCLUSIONS: The teaching of EBM course at the Faculty of Medicine, Ramathibodi Hospital is useful for medical students to enhance their critical thinking skills, and they seem to value the sessions positively.

Transcoronary infusion of bone marrow derived multipotent stem cells to preserve left ventricular geometry and function after myocardial infarction.

BACKGROUND: 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. HYPOTHESIS: Transcoronary infusion of bone marrow derived multipotent stem cells into infarcted related artery after acute myocardial infarction is feasible, safe and improve left ventricular function. METHODS: We conducted a pilot study in patients who survived ST-elevation MI with late reperfusion therapy and remained hemodynamically stable. Bone marrow derived MSC was infused into a patent infarct-related coronary artery during brief low pressure (2 atm) balloon inflation. A 3-T gadolinium-based MRI was performed at baseline and 8 weeks later to evaluate infarct area and LV function. RESULTS: We enrolled 10 patients, age 63.8 +/- 2.8 years 5.2 +/- 4.12 x 10(6) MSC were infused via coronary artery 24.8 +/- 16 days after infarction. The procedures were successful in all patients without any in-hospital event. Infarct size by MRI decreased by 5.84% (P = .018) over 8 weeks. Mean baseline left ventricular ejection fraction (LVEF) was 44.1% +/- 9% and was 46.3% +/- 9% at 8 weeks (P = .34). A trend of smaller LV end-systolic volume with 65.02 +/- 18.2 ml vs 63.04 +/- 21.89 ml (P = .09) with no change of LV end-diastolic volume observed. CONCLUSION: MSC infusion into coronary circulation was feasible and safe after myocardial infarction. Infarct size was reduced with preservation of LV geometry.

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

BACKGROUND: Thalidomide 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. RESULTS: Induction 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. CONCLUSIONS: Prolonged thalidomide therapy enhanced survival rate and less frequently developed serious toxicity in non-transplant multiple myeloma patients.

Reduced intensity stem cell transplantation for treatment of class 3 Lucarelli severe thalassemia patients.

Bone marrow transplantation is the only therapeutic option that can potentially eliminate thalassemic disease. Early results indicated that children in Class 3 Lucarelli had a much worse outcome because of high nonrejection mortality and high rejection rate. In the present study, reduced intensity stem cell transplantation (RIT) was performed in eight Class 3 Lucarelli patients conditioned by busulfan, fludarabine, and antilymphpcute globulin. One of the eight patients additionally received thiotepa, and total lymphoid irradiation (TLI), while one only received TLI. All patients received hydroxyurea 20 mg/kg/day daily >/=3 months before RIT. Peripheral blood stem cell (PBSCs) were given to a target number of CD34(+) cells more than 5 x 10(6) cells/kg of recipient weight. Seven patients received T cell nondepleted PBSCs from matched siblings while one patient received purified CD34(+) cells from two HLA antigen mismatched maternal PBSCs. The graft-versus-host disease (GvHD) prophylaxis included cyclosporine or tacrolimus and mycophenolate mofetil. Initially, an engraftment of donor cells was observed in all eight patients, but subsequently only six of eight patients had stable full donor engraftment. There were no deaths or Grade 3-4 acute GvHD in our patients. The present study lends support that the regimens described here produced minimal toxicity and resulted in stable full donor engraftment in the majority of the severe Class 3 Lucarelli thalassemia patients.

Outcomes of transplantation with related- and unrelated-donor stem cells in children with severe thalassemia.

Recently published reports indicate that the outcome of unrelated donor transplantations in patients with leukemia is currently comparable to that of transplantation from identical family donors. We investigated the possibly favorable outcomes of related and unrelated transplantation in children with severe thalassemia. We reviewed transplantation outcome in 49 consecutive children with severe thalassemia who underwent allogeneic stem cell transplantation with related-donor (n=28) and unrelated-donor (n=21) stem cells between September 1992 and May 2005 at the Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Bangkok, Thailand). Analysis of engraftment, frequency of procedure-related complications, and thalassemia-free survival showed no advantage from use of related-donor stem cells. The 2-year thalassemia-free survival estimate for recipients of related-donor stem cells was 82% compared with 71% in the unrelated-donor stem cell group (P=.42). The present study provides evidence to support the view that it is quite reasonable to consider unrelated-donor stem cell transplantation an acceptable therapeutic approach in severe thalassemia, at least for patients who are not fully compliant with conventional treatment and do not yet show irreversible severe complications of iron overload.