Cytomegalovirus Ventriculoencephalitis after Unrelated Double Cord Blood Stem Cell Transplantation with an Alemtuzumab-containing Preparative Regimen for Philadelphia-positive Acute Lymphoblastic Leukemia

Despite the prophylaxis and preemptive strategies using potent antiviral agents, cytomegalovirus (CMV) remains a major infectious cause of morbidity and mortality in allogeneic stem cell transplantation (SCT) recipients. Delayed immune reconstitution after SCT, such as cord blood and T-cell depleted SCT with the use of alemtuzumab, has been associated with an increased frequency of CMV disease as well as CMV reactivation. CMV disease involving central nervous system is an unusual presentation in the setting of SCT. We report a case of CMV ventriculoencephalitis after unrelated double cord blood SCT with an alemtuzumab-containing preparative regimen for Philadelphia-positive acute lymphoblastic leukemia.

A Case Report of the Second de Novo Acute Myeloid Leukemia (AML) Following Allogeneic Stem Cell Transplantation in a Patient with the First AML

Secondary leukemia occurring after hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) is rare. Secondary AML usually follows autologous and not allogeneic transplants. When a new leukemia develops in a patient successfully treated with an allogeneic HSCT, the possibility of a de novo or secondary leukemia from either the donor or recipient should be considered. We present a case initially diagnosed as de novo AML without a cytogenetic abnormality. The patient was successfully treated with an HLA-matched sibling allogeneic HSCT. However, more than six years later, AML developed again and was associated with new complex cytogenetic abnormalities. After a second HSCT, the patient has been followed without serious complications. Considering the allogeneic setting, the newly developed cytogenetic abnormalities, a relatively long latent period, and the good clinical course after the second allogeneic HSCT, this case might represent a second de novo AML following successful treatment of the first AML.

Characteristics of Cytomegalovirus Diseases among Hematopoietic Stem Cell Transplant Recipients : A 10-year Experience at an University Hospital in Korea / 감염과화학요법

BACKGROUND: Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. METHODS: Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. RESULTS: Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%; the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. CONCLUSIONS: We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

Bone Marrow T Cells are Superior to Splenic T Cells to Induce Chimeric Conversion After Non-Myeloablative Bone Marrow Transplantation

BACKGROUND/AIMS: The bone marrow functions not only as the primary B-lymphocyte-producing organ but also as a secondary lymphoid organ for CD4 and CD8 cell responses and a site of preferential homing and persistence for memory T cells. Bone marrow T (BM-T) cells are distinguished from peripheral blood T cells by surface phenotype, cytokine secretion profile, and immune functions. In this study, we evaluated the alloreactive potential of donor lymphocyte infusion (DLI) using BM-T cells in mixed chimerism compared to that using spleen T (SP-T) cells. METHODS: Cells were prepared using established procedures. BM-T cells were obtained as a by-product of T-cell depletion in BM grafting and then cryopreserved for subsequent DLI. We performed DLI using BM-T cells in allogeneic mixed chimera mice on post-BMT day 21. RESULTS: When the same dose of T cells, 5-10x10(5) (Thy1.2+), fractionated from BM and spleen were administered into mixed chimeras, the BM-T group showed complete chimeric conversion, with self-limited graft-versus-host disease (GVHD) and no pathological changes. However, the SP-T group showed persistent mixed chimerism, with pathological signs of GVHD in the liver and intestine. CONCLUSIONS: Our results suggest that DLI using BM-T cells, even in small numbers, is more potent at inducing chimeric conversion in mixed chimerism than DLI using SP-T cells. Further study is needed to determine whether cryopreserved BM-T cells are an effective cell source for DLI to consolidate donor-dominant chimerism in clinical practice without concerns about GVHD.

Oral Beclomethasone Dipropionate for the Treatment of Steroid-refractory Gastrointestinal Acute Graft-versus-host Disease

Acute graft-versus-host disease (GVHD) is one of the most severe complications following allogeneic stem cell transplantation (SCT), and involvement of the gut has been associated with increased mortality and a poorer response to high-dose systemic corticosteroids. For over a decade, oral beclomethasone dipropionate (BDP) has been studied in the treatment of acute gastrointestinal GVHD, as a monotherapy, or in combination with systemic corticosteroids. Here we report, for the first time in Korea, the efficacy of oral BDP (8 mg/day for 25 days) in 3 adults with acute lymphoblastic leukemia who developed steroid-refractory gastrointestinal GVHD (grade III) after myeloablative conditioning SCT (1 matched sibling transplant, 2 matched unrelated transplants). All patients responded completely to oral BDP treatment. Oral BDP is safe and effective for the control of steroid-refractory acute gastrointestinal GVHD.

Characteristics of Cytomegalovirus Diseases among Hematopoietic Stem Cell Transplant Recipients : A 10-year Experience at an University Hospital in Korea / 감염과화학요법

BACKGROUND: Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. METHODS: Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. RESULTS: Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%; the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. CONCLUSIONS: We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

Comparison of Quantitative Cytomegalovirus Real-time PCR in Whole Blood and pp65 Antigenemia Assay: Clinical Utility of CMV Real-time PCR in Hematopoietic Stem Cell Transplant Recipients

Successful preemptive therapy for cytomegalovirus (CMV) infection in transplant patients depends on the availability of sensitive, specific, and timely diagnostic tests for CMV infection. Although the pp65 antigenemia assay has been widely used for this purpose, real-time quantification of CMV DNA has recently been recognized as an alternative diagnostic approach. However, the guidelines for antiviral therapy based on real-time quantitative polymerase chain reaction (RQ-PCR) have yet to be established. From November 2004 to March 2005, a total of 555 whole blood samples from 131 hematopoietic stem cell transplant (HSCT) recipients were prospectively collected. RQ-PCR was conducted using an Artus(R) CMV LC PCR kit (QIAGEN). Both qualitative and quantitative correlations were drawn between the two methods. Exposure to the antiviral agent influenced the results of the two assays. Additionally, the discrepancy was observed at low levels of antigenemia and CMV DNA load. Via ROC curve analysis, the tentative cutoff value for preemptive therapy was determined to be approximately 2x10(4) copies/mL (sensitivity, 80.0%; specificity, 50.0%) in the high risk patients, and approximately 3x10(4) copies/mL (sensitivity, 90.0%; specificity, 70.0%) in the patients at low risk for CMV disease. Further study to validate the optimal cutoff value for the initiation of preemptive therapy is currently underway.

Bortezomib Therapy Followed by Autologous Stem Cell Transplantation in POEMS Syndrome

BACKGROUND: The acronym POEMS refers to polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. Increased levels of cytokines, including vascular endothelial growth factor (VEGF), appear to play a pathogenic role. POEMS syndrome is progressive and eventually leads to death from neurological problem without therapy. METHODS: We treated 3 patients affected by POEMS syndrome with front-line bortezomib treatment and the high-dose melphalan with autologous stem cell transplantation (ASCT). RESULTS: Bortezomib reduced circulating levels of VEGF in sera. After a median follow-up of 18 months (range, 16~20), all patients are alive with progressive improvement in neurological disease, skin changes, performance status and have no evidence of clonal plasmacytosis or organomegaly. CONCLUSION: ASCT following bortezomib treatment may be a potential treatment option for patients with POEMS syndrome.

Four cases of chloroma treated with hematopoietic stem cell transplantation / 대한내과학회지

Chloroma is an invasive extramedullary tumor composed of immature myeloid cells, which complicates the clinical course in a minority of patients with acute myeloid leukemia (AML). The presence of myeloid sarcoma is known to be a poor prognostic indicator in patients with AML. However, the optimal treatment of AML with concurrent chloroma has not been determined. We report four patients with AML accompanied by concurrent chloroma from the time of initial diagnosis. All of the patients underwent hematopoietic stem cell transplantation after complete remission. We also present a review of the literature.

Air-leakage syndrome after allogeneic peripheral blood stem cell transplantation from unrelated donor / 대한내과학회지

Bronchiolitis obliterans, a late, non-infectious pulmonary complication of bone marrow transplantation (BMT), is an obstructive airway disease associated with chronic graft-versus-host disease (cGVHD). We report a rare case of air-leakage syndrome including pneumothoraces, pneumomediastinum, and subcutaneous emphysema with bronchiolitis obliterans after allogeneic peripheral blood stem cell transplantation (PBSCT) from an unrelated donor. The pathogenesis of air-leakage syndrome is not fully understood, and its management has not yet been established. This patient was treated with high-concentration oxygen, tube thoracostomy, percutaneous drainage with a pigtail catheter to relieve the tension pneumomediastinum, and mechanical ventilatory support. The patient has now recovered and is being followed on an outpatient basis.

Three cases of Philadelphia (Ph) chromosome positive acute myeloid leukemia (AML) treated with imatinib mesylate (Glivec, STI571) and allogeneic hematopoietic stem cell transplantation after induction chemotherapy / 대한내과학회지

The Ph-chromosome is the hallmark of chronic myelogenous leukemia (CML), but it has also been reported infrequently for de novo AML. This cytogenetic variant of AML is characterized by a poor prognosis associated with extraordinary drug resistance. Experience with the use of imatinib mesylate for Ph-chromosome-positive de novo AML is limited because of the rarity of the disorder. Thus, allogeneic hematopoietic stem cell transplantation (HSCT), as a post-remission therapy, should be considered. In three patients with Ph-chromosome-positive AML, we achieved complete remission with induction chemotherapy and the use of an imatinib cycle as an interim therapy. Subsequently, all patients received consolidation chemotherapy followed by imatinib cycles, bridging the time to allogeneic HSCT. All patients were successfully transplanted, and have been in excellent condition, with a median follow-up duration of 15 months (range, 2-25 months). We report on these cases and present the treatment strategy of induction chemotherapy, maintenance with imatinib mesylate, and final allogeneic HSCT as a representative paradigm for the treatment of Ph-chromosome-positive de novo AML.

Effect of Extracorporeal Photopheresis on Steroid Resistant Acute GVHD Refractory to High Dose Steroid Treatment

BACKGROUND: The mortality of patients with steroid resistant acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is high due to multiple organ failure and infection. Recently, the use of extracorporeal photopheresis (ECP), which is believed to have a low risk of infection, has been applied for the treatment of GVHD. METHODS: Of 23 patients who were steroid resistant acute GVHD that was resistant even to high dose steroid treatment as second-line treatment, 10 patients received ECP (ECP group) and 13 patients received a third-line treatment other than ECP (non-ECP group). The outcome including the response rate and survival for the ECP group and non-ECP group was analyzed. RESULTS: The response rate of the ECP group including complete remission and partial remission, was 30%. The survival rate was 30% for the ECP group and 0% for the non-ECP group. The estimated mean survival time was 229.3+/-89.3 days for the ECP group and 41.8+/-14.6 days for the non-ECP group (P=0.028). CONCLUSION: ECP can be considered as a treatment option for the steroid resistant acute GVHD that is refractory to high dose steroid treatment.

Susceptibility of Leukemia according to the Genotype of Minor Histocompatibility Antigens in a Korean Population

BACKGROUND: In the search for susceptibility genes responsible for leukemia, genetic studies involving HLA association have been in progress extensively since the first report on its effect on the disease. Here we investigated the genetic associations of different leukemias with 4 autosomal mHags, HA-1, -2, -8 and HB-1. In particular, HB-1 is one of the leukemia-associated minor histocompatibility antigens (mHags) that is significantly expressed by Epstein-Barr virus-transformed- and tumor cells of all B lineage acute lymphoblastic leukemia (ALL). METHODS: A simultaneous genotyping method using PCR sequence-specific primers against HA-1, -2, -8 and HB-1 was developed, and their allelic frequencies in 139 healthy controls and 36 leukemia patients were observed. To compare genotype, phenotype, and gene frequencies of mHags with healthy controls, leukemia patients were classified into sub groups of ALL, acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). RESULTS: The genotype frequencies of HA-1, -2 and -8 were not significantly different from healthy controls in every group of leukemia patients. However, the HB-1 H genotype was significantly increased in leukemia patients (P=0.03, OR=1.82, CI=1.08~3.06), particularly in AML (P=0.01, OR=2.4, CI=1.21~4.76) as compared with healthy controls. CONCLUSION: Our results suggested that the genotype of HB-1 H may be associated with leukemia, particularly with AML. In further study, it is necessary to confirm the association of HB-1 with other leukemias in a larger group of patients, and to identify the underlying mechanism of HB-1 responsible for the occurrence of leukemia.

Practical Evaluation of Engraftment and Mixed Chimerism Using PCR Amplification of a Microsatellite in the Class II Eb Gene in Murine MHC-mismatched, Nonmyeloablative Bone Marrow Transplantation

BACKGROUND: Although engraftment following murine allogeneic bone marrow transplantation (BMT) is most commonly confirmed by H2 typing using flow cytometry, recipient mice can be seriously injured during peripheral blood (PB) sampling. Therefore, we developed an alternative DNA-based assay that does not require the large volume of PB necessary for flow cytometry. METHODS: A minute volume of PB from the tail vein was used to evaluate the engraftment by PCR amplification of a microsatellite in the class II Eb gene. Dilution experiments were performed to evaluate the sensitivity of this assay for detecting donor cells in mixed cell populations compared with flow cytometry analysis. RESULTS: Early engraftment and mixed chimerism were confirmed, based on the length variation of the microsatellite in the class II Eb gene. The degree of donor chimerism in the donor-recipient cell mixture could be estimated semiquantitatively in a dilution experiment. The sensitivity of this assay by the naked eye approached 10% of the degree of donor chimerism. CONCLUSION: PCR amplification of a microsatellite in the class II Eb gene can be a useful alternative to flow cytometry for evaluating early engraftment and mixed chimerism following murine nonmyeloablative BMT.

Hematopoietic Stem Cell Transplantation with Using Multinational Unrelated Donors for Acute Myelogenous Leukemia

BACKGROUND: Many AML patients have received hematopoietic stem cell transplantation (HSCT) from HLA-matched unrelated donors. According to many of the previous reports, those patients could achieve long-term, disease-free survival after HSCT from multinational unrelated donors with tolerable transplant-related complications, even when there are HLA-mismatches. METHODS: We present the results of 35 unrelated hematopoietic stem cell transplantations from multiple international donor banks including the Korean (n=24), and Japan Marrow Donor Program (n=3), the Taiwan Tzu Chi Marrow Donation Registry (n=6), as well as using Caucasian donors from the National Marrow Donor Program (n=2), for the treatment of AML patients. RESULTS: The median age of patients was 36 (range: 16~53) and the median follow-up duration was 21 months (range: 5~60). Also, the median age of the donors was 28 (range: 20~53). The majority of the patients had intermediate or unfavorable cytogenetic features. The main conditioning regimen we used consisted of cyclophosphamide plus TBI (n=31) with our standard GvHD prophylaxis that contained tacrolimus plus a short course of methotrexate. Some patients (n=10) received an additional two-day course of ATG (thymoglobulin, Sangstat) in addition to the standard regimen. All the transplanted patients achieved engraftment. The incidence of acute GvHD was 42%, and that of chronic GvHD was 56%. Four (11%) patients have relapsed to date. The two-year non-relapse transplant-related mortality was 26%. The estimated probability of DFS and the event-free survival at five-years were 80% and 53%, respectively. CONCLUSION: These results suggest that multinational unrelated donors HSCT may provide a feasible option for the treatment of high-risk Korean AML patients.

Viruria in Adult Hemorrhagic Cystitis Patients Following Allogeneic Hematopoietic Stem Cell Transplantation and Implication of Antiviral Treatment

BACKGROUND: Viruria is frequently detected in patients who have had hemorrhagic cystitis (HC) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Urinary viruses, especially BK virus, have been suggested as a cause of HC following allo-HSCT, therefore antiviral therapy is emerging as a therapeutic approach for its treatment. METHODS: Adult HC patients who underwent allo-HSCT from January 2005 to March 2006 at a single institution were enrolled. We performed a PCR-based assay for BK virus, JC virus, and CMV virus in urine obtained from the patients to determine the incidence of viruria, and the type of virus detected in the urine, and the effect of treatment with cidofovir on HC. RESULTS: Of 155 patients that received allo-HSCT during the study period, 22 (14.2%) experienced HC. A viral study of urine obtained from 19 of these 22 patients revealed that 16 (84.2%) had viruria. Eleven patients had grade III-IV HC, 5 of which were treated with intravenous cidofovir. Three of the HC patients who underwent treatment responded to cidofovir, 1 had no response, and 1 had a complete response followed by recurrence. CONCLUSION: Most adult HC patients (84.2%) had viruria following allo-HSCT, however the response rate to antiviral therapy with intravenous cidofovir for the treatment of high grade HC (grade III-IV) was 80%. Therefore, antiviral therapy should be considered if high grade HC does not respond to hyperhydration and transfusional support.

Distribution of Human Cytomegalovirus gB Genotypes and Its Association with Diseases in Hematopoietic Stem Cell Transplant Recipients in Korea; A Preliminary Report / 감염과화학요법

BACKGROUND: Human cytomegalovirus (HCMV) glycoprotein B (gB) is the major envelope glycoprotein, encoded by the UL55 gene. Based on sequence variation in the UL55 gene, HCMV can be classified into four gB genotypes. Previous studies have suggested an association between HCMV gB genotypes and clinical outcome in the immunocompromised hosts. The goal of this study was to determine the distribution of HCMV gB genotypes and the effect of gB genotype in the developement of HCMV diseases in hematopoietic stem cell transplant (HSCT) recipients in Korea. MATERIALS AND METHODS: DNA was extracted from 94 blood specimen of 52 allogeneic HSCT recipients with HCMV infection. HCMV gB genotype was determined using polymerase chain reaction to amplify a region of UL55, followed by restriction fragment length polymorphism (RFLP) analysis based on RsaI and HinfI digestion. RESULTS: The distribution of gB types were as follows: gB1, 73.1% (38/52) of patients; gB2, 13.5% (7/52); gB3, 1.9% (1/52) and mixed infection (gB1 and gB2), 9.6% (5/52). While gB4 was not detected, a new genotype (described as gB7 by Trincado et al, 2000) was identified on the basis of their RFLP pattern. During average 708 days' follow up period, HCMV diseases developed in 5 patients. All of them had gB1 genotype. There was no statistically significant association between the incidence of HCMV diseases and the gB genotypes. Re-infection with gB1 strain was detected in one patient who had been previously infected with gB2. This episode was associated with fever, elevated liver enzyme and positive antigenemia. CONCLUSION: HCMV gB1 was the dominant genotype and no gB4 was detected in allogeneic HSCT recipients in Korea, which is an unique pattern compared with the previous reports. Although we can not find significant association between the HCMV diseases and the gB genotypes, genotyping of HCMV will serve in the study of pathogenesis and transmission of this virus in transplant patients. Further study is underway with large study population.

Distribution of Human Cytomegalovirus gB Genotypes and Its Association with Diseases in Hematopoietic Stem Cell Transplant Recipients in Korea; A Preliminary Report / 감염과화학요법

BACKGROUND: Human cytomegalovirus (HCMV) glycoprotein B (gB) is the major envelope glycoprotein, encoded by the UL55 gene. Based on sequence variation in the UL55 gene, HCMV can be classified into four gB genotypes. Previous studies have suggested an association between HCMV gB genotypes and clinical outcome in the immunocompromised hosts. The goal of this study was to determine the distribution of HCMV gB genotypes and the effect of gB genotype in the developement of HCMV diseases in hematopoietic stem cell transplant (HSCT) recipients in Korea. MATERIALS AND METHODS: DNA was extracted from 94 blood specimen of 52 allogeneic HSCT recipients with HCMV infection. HCMV gB genotype was determined using polymerase chain reaction to amplify a region of UL55, followed by restriction fragment length polymorphism (RFLP) analysis based on RsaI and HinfI digestion. RESULTS: The distribution of gB types were as follows: gB1, 73.1% (38/52) of patients; gB2, 13.5% (7/52); gB3, 1.9% (1/52) and mixed infection (gB1 and gB2), 9.6% (5/52). While gB4 was not detected, a new genotype (described as gB7 by Trincado et al, 2000) was identified on the basis of their RFLP pattern. During average 708 days' follow up period, HCMV diseases developed in 5 patients. All of them had gB1 genotype. There was no statistically significant association between the incidence of HCMV diseases and the gB genotypes. Re-infection with gB1 strain was detected in one patient who had been previously infected with gB2. This episode was associated with fever, elevated liver enzyme and positive antigenemia. CONCLUSION: HCMV gB1 was the dominant genotype and no gB4 was detected in allogeneic HSCT recipients in Korea, which is an unique pattern compared with the previous reports. Although we can not find significant association between the HCMV diseases and the gB genotypes, genotyping of HCMV will serve in the study of pathogenesis and transmission of this virus in transplant patients. Further study is underway with large study population.

Autologous Stem Cell Transplantation using a Modified TAM Conditioning Regimen for Clinically Aggressive Non-Hodgkin's Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: High-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) have been used for the treatment of clinically aggressive non-Hodgkin's lymphoma (NHL). However, the superiority of specific conditioning regimens has not yet been established. The present study evaluated the efficacy and toxicity of a conditioning regimen involving fractionated total body irradiation (TBI), and the use of Ara-C and melphalan (TAM) for clinically aggressive NHL. MATERIALS AND METHODS: Between March 2002 and December 2004, 31 patients with aggressive NHL received fractionated TBI with a dose of 12 Gy over 3 days, and were administered 9 g/m2 Ara-C and 100 mg/m2 melphalan followed by autologous peripheral blood stem Cell Transplantation at the Catholic Hematopoietic Stem cell transplantation Center Korea. Patients that responded to first line chemotherapy and achieved complete remission (CR), or were in a first sensitive relapse were defined as having less advanced disease, while the other patients were defined as having more advanced disease. RESULTS: Objective responses were obtained in 24 of 31 patients (77.4%), comprising complete remission in 19 patients (61.3%) and partial remission in 5 (16.1%) patients. The median follow-up time was 28 months (range 1~62 months). At 3 years, the overall survival and event-free survival (EFS) rates were 62.3% and 47.3%, respectively. Patients with less advanced disease and more advanced disease showed 3-year EFS rates of 73.3% and 22.5 %, respectively (p=0.006). Early (within the first 100 days) treatment-related mortality occurred in 3 (9.7%) patients. Of the 31 total patients, 15 (48.4%) developed grade 3 mucositis, 22 (70.9%) developed neutropenic fever, and two (6.5%) developed interstitial pneumonia syndrome >grade 3. CONCLUSION: The modified TAM conditioning regimen and ASCT appear to be a feasible treatment regimen for clinically aggressive NHL, particularly for patients with less advanced disease.

A Case of Acute Promyelocytic Leukemia after Iodine-131 Treatment for Thyroid Cancer

Radioactive iodine (131I) has been used in the treatment of thyroid cancer to eliminate residual thyroid tissue after thyroidectomy and to treat metastatic disease. Leukemia has rarely been reported as a late complication of 131I therapy, occurring most frequently after receiving a cumulative activity of 800 mCi of the radioisotope. Although FAB M3 type (acute promyelocytic leukemia, APL) as the secondary acute leukemia had been rarely reported, recently there have been a few cases of therapy-related APL leukemia seen. We hereby report a case of secondary acute promyelocytic leukemia occurring in a patient who received radioactive iodine therapy for papillary thyroid carcinoma. An assessment of causality using the Naranjo probability scale showed that a possible relationship existed between APL seen in the patient and the use of the radioactive iodine. Although this is a very rare event, strict hematologic follow-up of patients treated with radioactive iodine may be warranted, along with a high index of suspicion in those with coagulopathy.