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Purpose Orteronel (TAK-700) is a non-steroidal, selective, reversible inhibitor of 17,20-lyase. We evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effect of orteronel with or without prednisolone in Japanese patients with castration-resistant prostate cancer (CRPC). Methods We conducted a phase 1 study in men with progressive and chemotherapy-naïve CRPC. Patients received orteronel orally at doses of 200–400 mg twice daily (BID) with or without oral prednisolone (5 mg BID). Dose-limiting toxicity (DLT) was assessed during Cycle 1 (28 days). Patients could continue study treatment until any of criteria for treatment discontinuation were met. Gonadotropin-releasing hormone therapy was continued in patients without prior orchidectomy. Results Fifteen patients were enrolled and administered at least one dose of orteronel. No DLTs were reported during Cycle 1 in this study. Adverse events (AEs) were reported in all 15 patients. Most common AEs (>30 %) were hyperlipasemia (47 %), hyperamylasemia (40 %), and constipation (33 %). Acute pancreatitis (Grades 2 and 3) and pancreatitis (Grade 1) were complicated in three patients during the study. Dose-dependent increase in plasma orteronel concentrations was indicated over the 200–400 mg BID dose range. Prednisolone coadministered did not alter PK of orteronel. Serum testosterone was rapidly suppressed below the lower limit of quantification across all doses. Of 15 subjects, 13 achieved at least a 50 % reduction from baseline in prostate-specific antigen. Conclusions Orteronel at doses up to 400 mg BID was tolerable in Japanese CRPC patients. The present results support further evaluation of orteronel with or without prednisolone.

Brentuximab vedotin is an antibody–drug conjugate that selectively delivers the antimicrotubule agent monomethyl auristatin E into CD30-expressing cells. To assess its safety, pharmacokinetics, and efficacy in Japanese patients with refractory or relapsed CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma, we carried out a phase I/II study. Brentuximab vedotin was given i.v. on day 1 of each 21-day cycle up to 16 cycles. In the phase I part of a dose-escalation design, three patients per cohort were treated at doses of 1.2 and 1.8 mg/kg. In the phase II part, a dose of 1.8 mg/kg was given to 14 patients (nine with Hodgkin's lymphoma and five with systemic anaplastic large-cell lymphoma). The median number of treatment cycles was 16 (range, 4–16). In the phase I part, no dose-limiting toxicity event was observed. In the total population, common adverse events included lymphopenia (80%), neutropenia (65%), leukopenia (65%), and peripheral sensory neuropathy (60%). Grade 3/4 adverse events in more than two patients were lymphopenia (50%) and neutropenia (15%). The pharmacokinetic profile was similar to that observed in the previous studies in the USA. In the phase II part, six patients (67%) with Hodgkin's lymphoma achieved an objective response with 56% of complete response rate, and five patients (100%) with systemic anaplastic large-cell lymphoma achieved an objective response with 80% of complete response rate. These results show that brentuximab vedotin has an acceptable safety profile and promising antitumor activity in the Japanese population. This trial was registered in JAPIC Clinical Trials Information (JapicCTI-111650). This phase I/II study was to investigate the tolerability, safety and efficacy of brentuximab vedotin. This study indicates that 1.8 mg/kg brentuximab vedotin given every 3 weeks has a manageable safety profile and has high overall tumor response rate in Japanese patients with relapsed or refractory Hodgkin lymphoma or systemic anaplastic large-cell lymphoma.

Telomerase activity has been found in most common cancers, thus indicating that telomerase detection may be a useful marker in cancer diagnosis. The telomeric amplification protocol (TRAP) assay and RT-PCR are customarily used to detect telomerase activity and the expression of the associated genes in cells. However, these methods do not provide any information about telomerase activation at an individual cell level. To analyze cells separately, those cells have to be isolated by sometimes complicated method. The immunohistochemical detection of human telomerase reverse transcriptase (hTERT) is useful to detect telomerase positive cells in a background of non-cancerous cells. A method has been developed for the detection of intranuclear hTERT protein, in a subpopulation of hematopoietic cells, using concurrent staining of a cell surface antigen and multicolor flow cytometry. Only mouse monoclonal anti-hTERT antibody demonstrated the specific positivity in immunocytochemistry and immunofluorescent flow cytometry. Human leukemia and myeloma cell lines showed 100% positivity, whereas normal neutrophils showed 0% positivity. hTERT expression was analyzed in hematopoietic precursor cells of bone marrow samples using concurrent staining of surface CD34 antigen and intracellular hTERT protein and multi-parameter flow cytometry. CD34 positive cells demonstrated higher expression of hTERT than CD34 negative cells. A quick, easy and sensitive assay for determining the hTERT protein expression has been developed. Using this method and the multi-parameter nature of flow cytometry and its ability to identify cellular subpopulations will provide a better understanding of the mechanisms regarding the activation of telomerase.

Little information is available regarding central nervous system (CNS) relapse of adult leukemia after allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, we reviewed the data of 1226 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myelogenous leukemia (CML) who received first allogeneic HSCT between 1994 and 2004, using the database of the Kanto Study Group for Cell Therapy (KSGCT), and analyzed the incidence, risk factors, and outcome of patients with CNS relapse. Twenty-nine patients developed CNS relapse at a median of 296 (9-1677) days after HSCT with a cumulative incidence of 2.3%. Independent significant factors associated with CNS relapse included ALL as the underlying diagnosis (relative risk [RR] = 9.55, 95% confidence interval [CI] = 1.26-72.2, P = .029), nonremission at HSCT (RR = 2.30, 95% CI = 1.03-5.15, P = .042), the history of CNS invasion before HSCT (RR = 5.62, 95% CI = 2.62-12.0, P = 9.2 × 10−6), and the prophylactic intrathecal chemotherapy after HSCT (RR = 2.57, 95% CI = 1.21-5.46, P = .014). The 3-year overall survival (OS) after CNS relapse was 18%. In 7 of 29 patients with CNS relapse, leukemia was observed only in CNS. Three of 7 patients were alive without systemic relapse, resulting in 3-year survival after CNS relapse of 46%. Although the outcome of patients with CNS relapse was generally poor, long-term disease-free survival could be achieved in some patients.

There have been conflicting reports over the JAK2-V617F mutation status of platelets in chronic myeloproliferative diseases (CMPDs). The aim of this study was to analyse JAK2-V617F status, not only in granulocytes but also in platelets. The JAK2-V617F mutation was analysed in both granulocytes and platelets in 115 patients with CMPDs using direct sequencing. JAK2-V617F was detected in granulocytes from 71 of those patients, all 71 of whom also had platelet JAK2-V617F expression. The remaining 44 patients showed negative JAK2-V617F expression on granulocytes, but positive JAK2-V617F expression was detected on the platelets from nine of the 33 essential thrombocythaemia (ET) patients, one of the eight polycythaemia vera patients, and two of the three primary myelofibrosis patients. When ET patients were divided into three groups according to granulocyte and platelet JAK2-V617F status (both-positive, platelets-only positive and both-negative), the both-positive and platelets-only positive groups shared the clinical features of higher white blood cell count and frequent thrombosis. These results suggest that analysis of platelets is a more sensitive approach for detecting JAK2-V617F in CMPD patients than analysis of granulocytes. They also suggest that previous reports of the incidence of JAK2-V617F in CMPD patients, obtained using only analysis of granulocytes, could be underestimations.

BACKGROUND. Although studies comparing conventional imaging modalities with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) for the detection of lymphoma and although the relations between 18F-FDG-PET and histologic types were reported previously, most studies were not systematic and involved relatively small numbers of patients. METHODS. Two hundred fifty-five patients with lymphoma had their disease staged using 18F-FDG-PET, and 191 of those patients also were assessed using gallium-67 scintigraphy (67Ga). Disease sites were identified on a site-by-site basis using computed tomography scans and/or magnetic resonance imaging. The results of these conventional imaging modalities were compared with the results from 8F-FDG-PET and 67Ga, and correlations between the imaging results and pathologic diagnoses were evaluated by using the World Health Organization classification system. RESULTS. Of 913 disease sites in 255 patients, 18F-FDG-PET identified >97% of disease sites of Hodgkin lymphoma (HL) and aggressive and highly aggressive non-Hodgkin lymphoma. For indolent lymphoma, the detection rate of 18F-FDG-PET was 91% for follicular lymphoma (FL); 82% for extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, irrespective of plasmacytic differentiation; and approximately 50% for small lymphocytic lymphoma (SLL) and splenic marginal zone lymphoma (SMZL). The results from 67Ga were similar to those from 18F-FDG-PET for most histologic subtypes. However, the sensitivity of 67Ga was unexpectedly poor for FL, for mantle cell lymphoma (MCL), and for the nasal type of natural killer/T-cell lymphoma (NK/T-nasal), ranging from 30% to 38%. CONCLUSIONS. 18F-FDG-PET was useful for all histologic subtypes of lymphoma other than SLL and SMZL. Compared with 67Ga, the authors strongly recommend the use of 18F-FDG-PET in patients with FL, MCL, and NK-nasal. Cancer 2007. © 2007 American Cancer Society.

56歳, 男性. 1996年, 左腎細胞癌 (clear cell type, T3, N1, M0) に対し根治的左腎摘出術を施行され, その後1年間interferon α (IFNα) を投与された. 1998年11月, 両側肺に多発性転移巣を認めたためIFNα治療を再開されたが, 効果不良で, 2000年6月には右腎, 副腎にも転移巣が出現し, 部分切除を施行された. 移植前には右腸骨への転移も認めたが, 多発性肺転移巣に対し, 2001年3月, HLA一致同胞より骨髄非破壊的同種末梢血幹細胞移植を実施した. day28にT細胞キメリズムはすべてドナータイプとなった. 急性GVHD, 慢性GVHDともに併発し, GVHDのコントロールに難渋し, ステロイドの減量が困難であった. 原疾患の増悪に加え心不全と肺出血のため, day793に死亡された. 治療効果に関して, 肺の転移巣は縮小していたが, 右腎, 腸骨の転移巣は増大しており, 移植片対腫瘍効果の差が見られた.

BACKGROUND A major concern in the treatment of patients with acute myeloid leukemia (AML) is how to prevent disease recurrences. Although intensive consolidation therapy has proven useful, the effectiveness of maintenance therapy remains controversial. METHODS Seven hundred eighty-nine patients ages 15–64 (median: 45 yrs) with de novo AML received induction therapy, which consisted of cytosine arabinoside (at a dose of 100 mg/m2 on Days 1–7) and idarubicin (at a dose of 12 mg/m2 on Days 1–3). The patients who achieved complete remission (CR) were then randomized into groups that received either four courses of standard-dose consolidation therapy without maintenance (Arm A) or three courses of standard-dose consolidation and six courses of maintenance therapy (Arm B). RESULTS In total, 78.7% of patients achieved CR. The 5-year overall survival (OS) rate for the 789 eligible patients was 46.9%, and the disease-free survival (DFS) rate for the 621 patients who achieved CR was 32.9%. The 5-year OS rate for Arm A was 52.4%, and 58.4% for Arm B (P = 0.599). The 5-year DFS rate for the patients who achieved CR was 35.8% in Arm A and 30.4% in Arm B (P = 0.543). In analyzing the data according to the risk groups, no statistical difference was observed either in the 5-year OS rate or in the 5-year DFS rate between the 2 arms. CONCLUSIONS In the current study, the Japan Adult Leukemia Study Group's conventional postremission therapy (three courses of standard-dose consolidation and six courses of maintenance therapy) was replaced successfully by a shorter duration of four courses of standard-dose consolidation therapy without the need for additional maintenance therapy. Cancer 2005. © 2005 American Cancer Society.

To determine the clinical significance of the T helper 1(Th1)/T helper 2 (Th2) ratio in multiple myeloma, the intracellular IFN-gamma and IL-4 were analyzed by flow cytometry in 56 patients with multiple myeloma. The mean Th1/Th2 ratio of cases in the initial diagnosis phase and the refractory phase were higher than that of the control group. The mean serum beta-2-microglobulin in the high Th1/Th2 subgroup was significantly higher than that in the normal Th1/Th2 subgroup (P < 0.05). In conclusion, the Th1/Th2 ratio was closely related to the disease status of multiple myeloma.

Using our recently developed human androgen receptor (HUMARA) gene-based chimerism assay, long-term chimerism was investigated in female patients who underwent hematopoietic stem cell transplantation (HCT) with cells from male donors. After restriction digestion of samples, we detected a small number of female-derived cells within a large population of male-derived cells, with a sensitivity from 0.1% to 0.05%. Chimerism was examined in four patients with myeloid malignancies: two patients with acute myeloid leukemia (AML) from myelodysplastic syndrome (MDS), and one patient each with AML M3 and AML M4. All patients underwent myeloablative conditioning regimens and exhibited good clinical results during a median follow-up period of 6.6 years (range, 3.4-7.5 years). Female-derived cells were detected throughout the entire follow-up period in all bone marrow samples, but they became undetectable in the peripheral blood samples of 3 patients. Moreover, the HUMARA band pattern suggests that these residual host cells were normal cells. This study confirms the usefulness of the HUMARA gene-based assay, which showed that patients undergoing HCT frequently show mixed chimerism (MC) for a long period, especially in bone marrow, although the possibility of contamination by host stromal cells cannot be excluded.

We analysed the cell surface expression of chemokine receptors and natural killer receptors (NKRs) in addition to conventional T- and natural killer (NK)-cell markers in patients with lymphoproliferative disease of granular lymphocytes (LDGL), and compared results between NK- and T-LDGL subgroups. The subjects of this study were 15 LDGL patients: four NK-LDGL and 11 T-LDGL [six CD8(+) T-cell receptor (TCR) alphabeta(+), four CD4(+) TCRalphabeta(+) and one CD8(+) TCRgammadelta(+)] cases. Flow cytometric analysis showed that the expanding cells had a common phenotype, CD45RA(+) CD27(-) CD28(-) CCR7(-), in NK- and T-LDGL patients irrespective of differences in TCR status. There were no marked differences in the expression patterns of chemokine receptors between NK- and T-LDGL patients. Although restricted NKR subsets were expressed on both NK- and T-large granular lymphocytes (LGLs), CD94 was the most widely expressed marker. These findings may be unique to cells of LDGL cases, because normal CD56(dim) NK cells frequently express killer cell immunoglobulin-like receptors. Furthermore, analysis of NKR expression was repeated over an interval of more than 6 months, and fluctuations of NKR repertoire in the LGL clones were minimal.

Summary. We report 10 patients with T-cell large granular lymphocyte (LGL) leukaemia: four patients had CD16+ CD56− LGL lymphocytes (typical for LGL leukaemia), and six patients had CD56+ CD16dim/− LGL lymphocytes (atypical). Among the CD56+ CD16dim/− patients, LGL lymphocytes were CD4+ CD8− in one patient, CD4/CD8 double positive (DP) in three, and CD4− CD8+ in two. The CD4+ CD8dim DP cells expressed a CD8αα homodimer. T-cell receptor (TCR) Vβ complementarity-determining region 3 (CDR3) size distribution analysis and direct sequencing identified at least 1 in-frame clonal TCR Vβ transcript in each patient; three patients had two or three different clonal sequences. To determine whether these transcripts were translated into cell surface TCR, we performed flow cytometric analysis using Vβ monoclonal antibodies (mAbs). A single Vβ protein was identified in patients, even those with multiple in-frame transcripts. Previous and present results suggest that CD56+ CD16dim/− LGL leukaemia is more common than previously thought, and is associated with unusual phenotypes. When assessed using only molecular techniques, the monoclonal status of this disease may be misinterpreted as oligoclonal; thus, flow cytometric analysis using Vβ mAb is quite useful. Because mAbs do not cover the entire Vβ repertoire, assessing clonality using a combination of molecular methods and mAbs is preferable.

The AML1/ETO fusion gene is expressed in virtually all patients with t(8;21)(q22;q22) acute myelogenous leukemia (AML). Long-term complete remission (CR) of AML with t(8;21) has been observed despite the presence of residual AML1/ ETO fusion transcripts, although detection may depend on the sensitivity of the methods used. We examined a patient with recurrent AML who showed the t(8;21)(q22;q22) chromosomal abnormality following a CR of 15 years. The blast cells at the time of recurrence expressed the AML1/ETO fusion transcript, and the breakpoint of the AML1 gene was located on intron 5. Southern blot analysis of the DNA extracted from bone marrow slides that had been made and stored for 15 years revealed the same rearrangement pattern of the AML1 gene. Furthermore, the junction sequences between the AML1 and the ETO genes, analyzed by long-distance inverse polymerase chain reaction, proved to be completely identical. These findings can be interpreted in two ways: (1) The initial leukemia clone persisted and finally relapsed after 15 years in the dormant state. (2) AML developed in different subclones having the same AML1/ETO junctional sequences but with additional genetic changes (second hit).

To examine whether the percentage of myeloperoxidase (MPO)-positive blast cells is useful as a prognostic factor for acute myeloid leukemia (AML), cytochemical analysis of MPO was performed in 491 patients who were registered to the Japan Adult Leukemia Study Group-AML92 study. Patients were divided into two using the percentage of MPO-positive blast (high [>or=50%] and low (

Background and Aims : A diagnostic feature of chronic myelogenous leukemia (CML) is the presence of BCR/ABL fusion genes. There are two types BCR/ABL transcripts : CML-and acute lymphoblastic leukemia (ALL) -types. ALL-type BCR/ABL transcript is detectable in approximately 50% of CML patients, and its abundance is generally less than that of CML-type BCR/ABL. However, the exact stoichiometry has not been established. In this report, we sought to quantify these two types of BCR/ ABL transcripts in patients with CML in chronic phase (CP) by highly sensitive quantitative PCR methods. Methods : We examined two types of the BCR/ABL transcripts in seven patients with CML in chronic phase using reverse transcription and real-time quantitative polymerase chain reaction (RQ-PCR). The BCR/ABL expression was normalized to the expression of GAPDH. Results : In 5 out of 7 patients, ALL-type BCR/ABL could be detected. The ratio of CML-type BCR/ABL to GAPDH ranged from 4.94 × 10-3 to 81.8 × 10-3, and that of ALL-type to GAPDH ranged from 0.15 × 10-3 to 0.85 × 10-3. Thus, ALL-type transcript levels ranged from 1.3 to 54.3% of the CML-type levels. Conclusions : In CML patients, expression of ALL-type BCR/ABL was 1 to 2 orders of magnitude lower than expression of CML-type BCR/ABL..

近年, 前処置を軽減した骨髄非破壊的同種造血幹細胞移植 (Nonmyeloablative Stem Cell Transplantation;NST) が注目されている.NSTは「獲得したドナーT細胞による抗腫瘍効果」を期待した治療であり, 前処置の強度を弱めることで臓器毒性を減らし, 移植後早期の合併症による死亡のリスクを低下させることができる.この方法を用いれば白血病などの血液疾患治療の「切り札」である同種造血幹細胞移植を, 高齢者や臓器障害を有する症例にも実施可能であると考えられている.NSTの適応疾患に関する臨床試験が現在実施されているが, 血液疾患のみならず固形腫瘍の一部にも抗腫瘍効果が確認されている.当科でも治療抵抗性の5症例 (血液疾患4例, 固形腫瘍1例) に対しNSTを実施した.感染症対策は通常の急性白血病の化学療法と同様の管理で十分であり, 100日以内の早期死亡は見られなかった.2例にgradeIII以上の急性GVHDを併発し, 生着後の合併症対策は通常の同種造血幹細胞移植と同様に注意深い経過観察が必要であった.5例中4例に明らかな抗腫瘍効果を認めたが, 3例は原疾患の再増悪により死亡した.NSTの適応疾患, 安全性に関しては今後更に症例を積み重ねる必要があるが, 比較的安全に施行可能な同種造血幹細胞移植であり, 新たな治療戦略として有望視される.

Acute myeloid leukaemia (AML) with trilineage dysplasia (AML/TLD) is de novo AML recognized by the morphological dysplasia of three mature cell lines in the presence of leukaemic blasts. We studied the karyotypes of AML/TLD of patients with de novo AML, except for those with the French-American-British classification M3, who were enrolled onto the Japan Adult Leukaemia Study Group (JALSG)-AML 92 trial. Morphological and cytogenetic analyses were performed in 559 patients and TLD phenotype was found in 155 patients (27.7%). The 511 patients with informative morphological and cytogenetic data were classified into three groups according to karyotype: favourable, intermediate and adverse risk groups (92, 375 and 44 patients respectively). Normal karyotype was the most frequent as a total, and among both the non-TLD and TLD patients (164 patients 45.3% and 78 patients 52.7% respectively). All but one patient with AML/TLD was classified into the intermediate or adverse cytogenetic risk group. TLD phenotype was associated with lower remission rate and shorter overall survival but it did not influence disease-free survival. Although we did not find any specific cytogenetic abnormalities for AML/TLD, the rarity of favourable karyotypes among TLD patients indicates the biological difference between AML/TLD and AML/non-TLD.

In chronic myelogenous leukaemia (CML), clonal change occurs in all myeloid and B-cell lineages, but very rarely T-cell lineages. A detailed three-colour cytometric analysis of peripheral lymphocytes was performed in 22 patients with chronic-phase CML (CP-CML). CD45 gating analysis was used to discriminate between lymphocytes and basophils. The peripheral lymphocyte pool was comprised of a significant proportion of naive CD4 cells, defined by a CD4+45RA+ phenotype [47.0 +/- 19.6% (mean +/- SD) of the total CD4+ cells], and naive CD8 cells, defined by a CD8+CD45RA+CD28+ phenotype (35.1 +/- 19.7% of total CD8+ cells), even in patients with long disease duration. The percentage of CD8 naive T cells showed inverse correlation with age, whereas no correlation was observed with disease duration. Possible explanations for the preservation of naive lymphocytes include (1) that the naive T cells differentiated from co-existing normal stem cells or (2) that long-lived naive T cells persisted from the CML onset and expanded peripherally (thymus independent). Either mechanism or a combination of both mechanisms might contribute to maintaining the naive compartment size.

De novo acute basophilic leukemia (ABL) is a rare form of myeloid leukemia. The low prevalence of ABL makes it difficult to define its clinical characteristics and to establish an effective therapeutic protocol. We present here a case of de novo ABL in a 64-year-old Japanese man. The diagnosis of ABL depended on the following: (1) metachromasia with toluidine blue stain, (2) intracytoplasmic theta granules identified by electron microscopy, and (3) findings obtained from extensive immunophenotypic analysis. Although blast cells lacked basophil-specific antigens such as CDw17, CD88, and FcepsilonRI, an expression profile of cytokine receptors including CD116 (GM-CSF receptor), CD117 (c-kit), and CD123 (IL-3 receptor alpha) helped to define the cellular lineage in our case. The patient achieved complete remission with intensive chemotherapy composed of idarubicin and cytosine arabinoside and was disease free during the following 30 months. We propose that immunophenotyping, especially focusing on cytokine receptors, is useful in diagnosing ABL.

OBJECTIVES Hepatitis C virus infection has often been suggested as a possible cause of various kinds of autoimmune diseases. The aim of this study was to determine the relationship between chronic idiopathic thrombocytopenic purpura (ITP) and hepatitis C virus infection and to characterize the clinical features of anti-HCV antibody (HCVab) positive chronic ITP patients. SUBJECTS AND METHODS We studied HCVab in 79 patients with chronic ITP (25 males, 54 females, mean age 42.3 yr, range 11-86 yr) using the third-generation ELISA method. RESULTS HCVab was detected in 11 of the 79 patients (13.9%). Quantitative HCV-RNA studies showed a high serum concentration of HCV-RNA in these patients. The platelet counts in these 11 HCVab-positive patients (Group 1) were lower than in the 68 HCVab-negative patients (Group 2) [(2.6 +/- 0.9) versus (4.9 +/- 3.0) x 10(10)/L, respectively; p

The translocation t(6;9)(p23;q34) is detected infrequently in subtypes of haematological malignancies including acute myelogenous leukaemia (AML) and myelodysplastic syndrome (MDS). Although the t(6;9) leukaemia is commonly associated with bone marrow basophilia, the cytological characteristics of leukaemic cells are unclear. In the current study, we examined the in vitro effects of several cytokines on growth and differentiation of t(6;9) leukaemic cells. Isolated bone marrow mononuclear cells from four patients with t(6;9) (two MDS and two AML) were cultured for 14 d in the presence or absence of each cytokine. At the end of culture, viable cells were counted, and their histology was examined. Bone marrow cells obtained from 22 patients (10 AML, six AML from MDS, six MDS) lacking t(6;9) were used as controls. Compared with control cultures, significantly higher numbers of blasts appeared in the culture of bone marrow cells from t(6;9)-positive patients in response to stimulation with granulocyte colony-stimulating factor (G-CSF), granulocyte–macrophage CSF (GM-CSF) or interleukin 3 (IL-3). Stem cell factor (SCF) had little effect. Neutrophil counts were also significantly increased in the presence of G-CSF or IL-3. SCF and IL-3 were potent in increasing basophil counts from t(6;9)-positive cultures. These findings suggest that bone marrow cells obtained from t(6;9) patients are highly sensitive to growth- and/or differentiation-promoting cytokines. Special attention should be paid to the use of ‘therapeutic’ cytokines in these patients.

非ホジキンリンパ腫intermediate grade 36例にCOPBLAM/MEVMP療法 (cyclophosphamide, vincristine, prednisolone, bleomycin, doxorubicin, procarbazine/mitoxantrone, etoposide, vindesine, meth-otrexate, prednisolone) を試みた.症例は男21例, 女15例で, 年齢は16から69歳 (中央値52歳), 臨床病期はI期1, II期5, III期10, IV期20例であった.全症例の完全寛解率 (CR) は69%, 5年生存率56%, 5年Event free survival (EFS) 42%であり, International Indexのlowとintermediate lowを合わせた5年生存率は71%, highとintermediate highを合わせた群では33%であった.副作用として骨髄抑制, 口内炎がみられ, 後半のMEVMPで目立ったが耐えうるものであった.MTX投与時期に若干の改良が必要であるが, 有用な治療法の一つと考えられた.

We report here the case of a 57-year-old Japanese man who developed nephrotic syndrome during the course of human immunodeficiency virus type 1 (HIV-1) infection. Histological examination revealed focal segmental glomerular sclerosis (FSGS), suggesting that HIV-associated nephropathy (HIVAN) was a possible diagnosis. However, he was initially treated with glucocorticoid plus immunosuppressants for primary FSGS, without knowledge that he was seropositive for HIV-1. Of importance, the nephrotic syndrome entered remission after treatment with cyclosporin A (CsA), and there was no recurrence of the nephropathy over the following 4 years. The patient eventually died due to opportunistic infection. This case is the first report of FSGS in a Japanese HIV patient, and also serves to illustrate the potential risks and benefits of CsA for the treatment of nephrotic syndrome associated with HIV-1 infection.

It is sometimes reported that the immunological abnormalities in myelodysplastic syndromes (MDS) induce autoimmune disease (i.e., acute systemic vasculitic syndrome, chronic cutaneous vasculitis, polyneuropathy, relapsing polychondritis, and steroid-responsive pulmonary disorders). We investigated the clinical features of patients with MDS accompanied by nephrotic syndrome. We enrolled 125 patients with MDS who were admitted between January 1979 and May 1996 in this study. The renal function was assessed based on the laboratory data and the findings at the physical examination. The diagnoses of nephrotic syndrome and glomerular disease were established when 24-hr urinary excretion was more than 3.5 g and serum total protein was less than 6.0 g/dl, and when the 24-hr protein excretion was more than 1.5 g. Five patients (4%) had glomerular disease, and three (2.4%) had nephrotic syndrome. Of the five patients with glomerular disease, two had refractory anemia (RA), and three had chronic myelomonocytic leukemia (CMMOL). Three of the total 11 patients with CMMOL were diagnosed as having nephrotic syndrome. Among the CMMOL patients, those with nephrotic syndrome showed higher absolute monocyte numbers than did those without nephrotic syndrome (8830 +/- 4677/microl vs. 3061 +/- 2887/microl, P = 0.03). One CMMOL patient was treated with VP-16 and hydroxyurea. As the white blood cell count in this patient decreased, the 24-hr urine protein excretion and the serum tumor necrosis factor alpha level decreased. The relationship between nephrotic syndrome and CMMOL was not clear. High monocyte count and the serum cytokines in MDS patients may play a partial role in the evolution of glomerulonephritis, and CMMOL may be closely related to nephrotic syndrome.

Using H-7, HA1001, FK506, cyclosporin A (CsA) and okadaic acid (OA), which are protein kinase and phosphatase inhibitors, we examined qualitative changes in hematopoietic precursor cells due to aging from the viewpoint of the role of protein kinases and phosphatases. Though H-7 and OA suppressed erythroid colony formation both in the elderly (age: 72-92, median: 86) and the young (age: 22-39, median: 29), no change due to aging was noted. HA1001 did not affect erythroid colony formation either in the elderly or the young. Erythroid colony formation was enhanced by FK506 and CsA in the young, however, erythroid colony formation was suppressed in the elderly. Similar examinations using cell fractions of non-T, non-macrophage, non-T + T, and CD34 positive cells were performed in both groups. Enhancement of erythroid colony formation in the young and suppression in the elderly by FK506 using unseparated MNC disappeared after removal of T cells. Enhancement of colony formation in the young and suppression of colony formation in the elderly were recovered when T cells were added again. The effects of FK506 and CsA on erythroid colony formation were thought to be the results of T cell inactivation, and the different sensitivity to FK506 and CsA in the elderly and young seemed to be the result of changes in the control mechanisms of hematopoiesis, such as the regulation of cytokine production by T cells, caused by aging.

An 18 year-old male was admitted to our hospital suffering from a large tumor which was located\nat the right frontal bone. He was diagnosed to have acute myeloid leukemia (AML) with granulocytic\nsarcoma (GS). A chromosomal analysis showed t(8; 21), and a flow cytometric analysis demonstrated\nthe leukemic cells to be positive for CD56.\nSystemic chemotherapy and radiation therapy to the GS, but the patient experienced a relapse in the\nlumbar vertebrae. He underwent an umbilical-cord blood stem cell transplantation, however, he died 7\nmonths thereafter. GS is a localized tumor consisting of leukemic myelolasts, which is generally\nobserved as a complication of either AML, myelodysplastic syndrome, or myelobproliferative disorders.\nWe herein report this case due to its rarity, even though various sites of GS have been reported.

Dear Editor:Angioimmunoblastic T cell lymphoma (AITL) is present in1–2% of non-Hodgkin lymphomas, which is associatedwith an aggressive clinical course and infectious complica-tions [1]. Aspergillosis is the most important factor ininfectious mortality among leukemia or lymphoma patientswith neutropenia. We describe a rare case of a patient withAITL who developed small-bowel perforation accompaniedby Aspergillus endocarditis, and who suffered discontinu-ous dull abdominal pain during chemotherapy.A 62-year-old Japanese man was admitted to ourhospital in December 2003 due to acute abdominal painand high fever. A physical examination revealed skin rash,anemia, superficial lymphadenopathy, and hepatospleno-megaly. His peripheral blood counts were hemoglobin,9.8 g/dl; WBC, 7.9×10

Leukemias of ambiguous lineage are uncommon, representing ∼4% of all leukemias [1] and have been categorized into three sub-types; undifferentiated acute leukemia, bilineal acute leukemia and biphe...

症例 : 43歳, 男性.主訴 : 発熱.近医にて貧血の経過観察中, 発熱出現し肺野異常陰影を指摘され, 精査加療目的に当科入院.発熱, 呼吸困難, 汎血球減少, 巨大肝脾腫, 両肺野の多発性腫瘤陰影を認めたが表在リンパ節は触知しなかった.胸腔鏡下肺生検にてリンパ腫様肉芽腫症と診断された.CHOP療法を開始も1クール終了時, 肺腫瘤影増大し無効と判断, MCNU-CHOP療法を開始した.肺腫瘤影はCT上1クール終了時36.8%, 2クール終了時には7.9%まで縮小した.また, その後の検討で本例は血管中心性B細胞性リンパ腫に一致し, 病変部にEpstein-Barrウイルスが証明された.本症は, 肺に血管中心性に多様な免疫細胞の浸潤を来す稀な疾患であり, 治療法も確立されていない.本症例はCHOP療法を早期に無効と判断し, MCNU-CHOP療法に変更して改善をみた一例であり, 本症に対する治療法確立に有用と考えられる.

A patient with myelodysplastic syndrome developed pericardial effusion 20 month after allogenic peripheral blood stem cell transplantation. Sclerotic and erythematous skin lesions were observed over the face and extremities, and a diagnosis of chronic graft vs. host disease (GVHD) was made based on skin biopsy findings. Pericardial fluid contained numerous CD8+/HLA-DR+ lymphocytes, but no leukaemic cells. Tumour necrosis factor alpha (TNFalpha) and soluble Fas (sFas) levels were highly elevated in both the effusion and serum. The patient was treated with methylprednisolone and tacrolimus. Skin GVHD improved rapidly associated with resolution of pericardial effusion and reductions in cytokine levels. We concluded that pericardial effusion was due to pericarditis and was a manifestation of chronic GVHD in this patient, and that cytotoxic lymphocytes and specific cytokines played significant roles.

We report three patients with pulmonary disorders associated with myelodysplastic syndromes (MDS). All three patients had symptoms of pyrexia and respiratory discomfort. One patient had pulmonary eosinophilia with bilateral pleural effusion, one had interstitial pneumonia, and one had bilateral pleural effusion caused by systemic vasculitis. Elevated C-reactive protein (CRP) levels, polyclonal hypergammaglobulinemia, and morphological abnormalities in peripheral blood were observed in all three patients. The bone marrow of these patients revealed trilineage dysplasia and eosinophilia. Cytogenetic analysis showed [46,XY,-7,+der(1q;7p)]. Antibiotic treatment was not effective. However, improvement was dramatic after corticosteroid treatment; CRP levels were reduced and the hypergammaglobulinemia was improved. These cases suggest that MDS with [-7,+der(1q;7p)] may be correlated with bone marrow eosinophilia and that an immunologic abnormality may be involved in the pulmonary disorders.

We retrospectively investigated air-leak syndrome (ALS), including pneumothorax and mediastinal/s.c. emphysema, following allogeneic hematopoietic SCT. Eighteen patients (1.2%) developed ALS among 1515 undergoing SCT between 1994 and 2005 at the nine hospitals participating in the Kanto Study Group on Cell Therapy. The median onset of ALS was at 575 days (range: 105-1766) after SCT and 14 patients (77.8%) had experienced late onset noninfectious pulmonary complications (LONIPC) before ALS. Chronic GVHD (cGVHD) was the strongest risk factor for ALS (odds ratio 13.5, P=0.013 by multivariate analysis). Repeat SCT, male sex and age

One hundred and twenty-two patients with multiple myeloma were classified as mature, intermediate, immature, or plasmablastic subtype according to Greipp's criteria. Contrary to Greipp's report, the survival time of plasmablastic myeloma was not significantly shorter than other subtypes, nor was the plasmablastic subtype identified as a poor prognostic factor. The survival time of mature plus intermediate myeloma was significantly longer than that of immature plus plasmablastic myeloma. Between the former and latter, significant differences were found for sex, clinical stage, thrombocytopenia, bone marrow plasmacytosis, renal insufficiency, bone destruction, and response rate to treatment. Therefore, it was suspected that the immature and plasmablastic subtypes were unfavorable prognostic factors in patients with multiple myeloma.

The present pilot study was designed to analyze the efficacy and toxicity of the association of natural α-interferon (nIFN), melphalan, and prednisolone in untreated patients with multiple myeloma. Nine patients were treated with conventional melphalan-prednisolone therapy. Another 15 patients were treated with the combination therapy of nIFN, melphalan and prednisolone. We concluded that treatment with nIFN is beneficial because of the good response rate and improvement in the synthesis of serum immunoglobulins. However, adverse reactions to nIFN were sever when the patients were treated with daily intramuscular injection of 6 × 106U/body of nIFN. Thus, we have started a randomized study which includes daily intramuscular injection of 3 × 106U/body of nIFN.

A 77-year-old female was referred to our hospital in March 1991 because of a severe bleeding tendency. Her blood count on admission was as follows: Hb 7.5 g/dl, WBC 4.6 x 10(9)/l with normal differentiation and platelet 2 x 10(9)/l. One month prior to admission, her blood count was normal. Initially, acute idiopathic thrombocytopenic purpura (ITP) was suspected, because of the acute onset of the bleeding tendency and thrombocytopenia. High dose intravenous immunoglobulin (400 mg/kg/day for 5 days) and bolus methylprednisolone (1 g/day for 3 days then tapered) were administered, starting March 13. Her platelet count had increased immediately on March 20 to 40 x 10(9)/l. However, platelet count decreased to 4 x 10(9)/l in the following two weeks. Her clinical course differed from that of typical acute ITP. Because the treatment with prednisolone was not effective, it was changed to intravenous infusion of vincristine (VCR) at a weekly dose of 1 mg for 6 weeks. The treatment was extremely effective, and her platelet count reached over 200 x 10(9)/l. The treatment was discontinued. Three weeks later, her platelet count decreased to 15 x 10(9)/l, the administration of VCR was resumed, and her platelet count recovered again. Throughout her clinical course, no side effect of VCR was noticed except for mild hypesthesia of the fingertips. VCR therapy was considered to be an useful treatment in elderly patients with ITP.

Ten years after being diagnosed with polycythemia vera, a 55-year-old woman required frequent blood transfusion due to secondary myelofibrosis. She underwent reduced-intensity stem cell transplantation (RIST) from an HLA-identical sibling donor. Since mixed chimerae were identified in the peripheral blood at day 35, cyclosporine was withdrawn. At day 73, she developed acute graft-versus-host disease of the liver, while simultaneous resolution of splenomegaly occurred and complete donor chimerism in the peripheral blood was achieved. Frequent red blood cell transfusion was required until day 300 after transplantation. Thus, RIST for an older patient with secondary myelofibrosis was successful without severe treatment-related morbidity. This case suggests that RIST could be an effective treatment modality for secondary myelofibrosis.

In Japan, typical hairy cell leukemia (HCL) is rare, and HCL-Japanese variant (HCL-JV) is more common. Hairy B-cell lymphoproliferative disorder (HBLD) is another unusual disorder of polyclonal B-lymphocytosis of hairy cell appearance. In the present study, we analyzed the clinical features of 3 patients with HCL, 3 with HCL-JV, and 3 with HBLD. All HBLD patients had the DRB1*04 allele. As compared with other B-cell lymphoproliferative disorders, CD27 expression on B cells was significantly lower in all patients, ranging from 0.3% to 23.4%. Our results suggest that low CD27 expression may be a distinct feature of these HCL-related disorders.

Immunologic abnormalities have been described in patients with Hodgkin lymphoma, including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). In this report, we describe a rare case of a 59-year-old woman who had autoimmune-mediated hepatitis and Hashimoto's thyroiditis at initial presentation of Hodgkin lymphoma. She was treated with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine), which induced a complete remission. One year later, she developed a sudden Coombs-positive hemolytic anemia and immune thrombocytopenia. She was diagnosed with Evans syndrome and was treated with prednisolone and intravenous immunoglobulin. However, the response of the therapies was poor; she died of progressive thrombocytopenia. The autopsy revealed the relapse of Hodgkin lymphoma of cervical lymph nodes. Although autoimmune disorders are described in Hodgkin lymphoma, our case shows a rare instance of a patient who had various immunologic abnormalities, including autoimmune-mediated hepatitis, Hashimoto's thyroiditis, AIHA, and ITP.

Candida guilliermondii (C. guilliermondii) are uncommon, representing approximately 1% of all Candida infections, but have been reported to show a higher rate of drug-resistance and mortality rate than C. albicans. Current guidelines for treatment of non-albicans candidemia in neutropenic patients now recommend the use of amphotericin B or voriconazole (VRCZ). We describe here the successful treatment for a 58-year-old male with azole-refractory C. guilliermondii fungemia by combination with liposomal (L-AmB) and micafungin (MCFG) therapy. He was diagnosed as having mantle cell lymphoma, and treatment with HyperCVAD (Rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) was started. Despite prophylactic treatment with fluconazole, he developed fungemia due to C. guilliermondii 41 days after the start of chemotherapy. Positive blood culture and high levels of (1--3)-beta-D-glucan persisted despite changing the treatment from fluconazole to voriconazole. Although L-AmB was also added to VRCZ, the clinical symptoms worsened. When MCFG was combined with L-AmB, the symptoms and data dramatically improved. Thus, combination therapy consisting of MCFG and L-AmB might be more effective against candidemia that is refractory to azole than combination therapy with VRCZ and L-AmB.

Disseminated intravascular coagulation (DIC) is one of the important complications to develop in patients with acute myeloid leukemia (AML). While acute promyelocytic leukemia (APL) is a strong risk factor for DIC, other clinical features have not been fully defined. We retrospectively analyzed 161 consecutive adult patients with de novo non-APL AML. DIC was diagnosed in 52 patients (32%); 28 patients at diagnosis and 24 soon after the initiation of induction chemotherapy. Leukocyte counts, C-reactive protein, and lactate dehydrogenase were significantly higher in the DIC+ group. Negative expressions of CD13, CD19, CD34, and HLA-DR were more prevalent in the DIC+ group. On multivariate logistic-regression analysis, variables that were independently associated with the development of DIC were high C-reactive protein, high leukocyte count, negative expressions of CD13 and HLA-DR, and cytogenetics with a normal karyotype or 11q23 abnormality. Although DIC is considered to be associated with serious morbidity and occasional mortality, we did not find any significant differences in the complete remission rate, overall or disease-free survival between DIC+ and DIC- groups. This study is the first to define the clinical characteristics associated with DIC in patients with non-APL AML, but exactly how and when DIC should be treated remains to be determined.

A 72-year-old woman was referred to our hospital for evaluation of leukocytosis revealed by a medical examination. Her physical examination demonstrated no splenomegaly and no palpable lymph nodes. Her white cell count was 10,900/microl with atypical lymphocytosis (84.5%). Her hemoglobin concentration was 10.4 g/dl, and platelet count 151,000/microl. On peripheral blood smears, the atypical lymphocytes had a hairy cell-like appearance, and phase-contrast microscopic and transmission electron microscopic findings revealed the lymphocytes had many long surface microvilli. Flowcytometric analysis of peripheral blood lymphocytes identified expanded B-lymphocytes as having the IgG+, CD5- CD10- CD11c+ CD19+ CD20+ CD23- CD25- and CD103- cell surface phenotype. Serum electrophoresis disclosed polyclonal elevation of IgG and IgM (2620 mg/dl and 840 mg/dl, respectively). No light-chain restriction and a polyclonal VH gene rearrangement pattern indicated the polyclonal proliferation of B cells. The patient was a nonsmoker and had HLA-DR4, as in previous reports which have suggested an association between hairy B-cell lymphoproliferative disorder (HBLD) and HLA-DR4. No chromosome 3 abnormality was observed. These findings were consistent with the characteristics of HBLD, but differed in some respects from those of persistent polyclonal B-cell lymphocytosis (PPBL). Therefore, we diagnosed this patient as having HBLD.

We present a case of a 74-year-old male, who had a relapse of minimal change nephrotic syndrome (MCNS) as the initial presentation of acquired hemophilia A. MCNS had been maintained in remission with prednisolone 10 mg for 15 years. In early December 2005, the patient developed edema of the right leg, was admitted to a local general hospital, and was diagnosed as having a relapse of MCNS based on massive proteinuria (urine protein 6.1 g/day). One week later, severe anemia (hemoglobin 4.4 g/dl) and acute renal failure (creatinine 2.0 mg/dl) developed, and a CT scan of the abdomen revealed a hematoma in the left iliopsoas muscle. He was referred to our hospital with bleeding tendency. Laboratory examination revealed prolonged APTT 80.5 seconds), reduced factor VIII activity (1%) and thepresence of factor VIII inhibitor at a titer of 19 Bethesda units/ml, based on which he was diagnosed as having acquired hemophilia A. With recombinant activated FVII, hemostasis was obtained and prednisolone administration 60 mg/day (1 mg/kg) was started. Both the acquired hemophilia A and MCNS responded well to the treatment with prednisolone. Six weeks after initiation of the treatment, factor VIII inhibitor and urine protein disappeared. This patient is considered to be a rare case; to the best of our knowledge, this is the third report of acquired hemophilia A with nephrotic syndrome.

症例は62歳, 男性.1996年6月7日, 汎血球減少症にて入院.骨髄にてperoxidase陽性芽球を44.2%, 3血球系統の形態異常を認め, acute leukemia (AML, M2) with trilineage dysplasiaと診断.6月8日よりidarubicin・cytosine arabinosideによる寛解導入療法開始.7月4日, 完全寛解に達したが, この頃より全身に紅色小丘疹出現.疥癬と診断し, hydrocortisone・crotamiton軟膏による治療を開始.地固め療法中, 一時皮疹は悪化したが, 同療法の継続にて軽快した.疥癬およびその重症型であるノルウェー疥癬は過去の疾患と考えられがちであるが, 現在でも免疫不全状態の患者を診療するにあたっては重要な疾患であり, 早期診断・治療が必要である.血液疾患の中では, 慢性の経過をとるリンパ系腫瘍との併発が多いが, AMLとのまれな併発例を経験したので報告する.

We retrospectively investigated the clinical characteristics of human herpesvirus 6 (HHV-6) meningoencephalitis within 100 days after allogeneic hematopoietic stem cell transplantation (HSCT). Of 1148 patients who received transplants between January 1999 and December 2003, 11 patients (0.96%) with HHV-6 meningoencephalitis were identified. Ten of 11 recipients received hematopoietic stem cells from donors other than HLA-identical siblings. Confusion was the most frequent central nervous system (CNS) symptom, and a skin rash with high-grade fever preceded the CNS symptoms in 9 patients. Magnetic resonance imaging of the brain showed an abnormal increased T2 signal in the hypothalamus of 5 patients. Eight patients were treated with ganciclovir, and an improvement of CNS symptoms was obtained in 3 patients; 3 patients treated with acyclovir showed no improvement. Improvement in the meningoencephalitis seemed less frequent in patients with abnormal findings in the hypothalamus than in those without such findings. Because the symptoms of HHV-6 meningoencephalitis mimicked those of cyclosporine- or tacrolimus-induced encephalopathy, the drugs were withdrawn at the onset of CNS symptoms in 10 patients, resulting in the development of grade IV graft-versus-host disease (GVHD) in 5 patients. Three patients died of HHV-6 meningoencephalitis, and 6 died of other causes, including GVHD. In conclusion, HHV-6 meningoencephalitis is a rare but potentially life-threatening complication in patients who undergo allogeneic HSCT. Careful assessment of the clinical findings and the brain may allow early and precise diagnosis of HHV-6 meningoencephalitis and contribute to improving its prognosis.

Sacroiliitis is the most pathognomonic and earliest manifestation of ankylosing spondylitis. We herein report a 28-year-old female patient who presented with sacroiliitis as an initial manifestation of acute myelogenous leukemia (AML). She had a 3-month history of anemia and walking difficulty. Bone marrow findings revealed an increase of blasts with trilineage dysplasia. Although she was initially diagnosed with myelodysplastic syndrome (MDS), blasts rapidly increased and AML developed 1 month after the diagnosis of MDS with Sacroiliitis. Induction chemotherapy failed to induce a complete remission of AML, but it did effectively treat the sacroiliitis. However, the sacroiliitis relapsed when the leukemia cells progressed thereafter. Oral corticosteroids helped ameliorate the sacroiliitis. She underwent bone marrow transplantation (BMT) from an HLA-identical sister during a nonremission period; however, the leukemic cells began to rapidly increase from day 30 after BMT. The close relationship between the occurrence of sacroiliitis and AML suggested that autoimmune sacroiliitis was a paraneoplastic phenomenon of AML in this patient. Although autoimmune disorders develop in a substantial number of MDS patients, they are rarely observed in de novo AML. No previous report has described sacroiliitis as the initial manifestation of de novo AML.

Immunologic abnormalities have been described in patients with Hodgkin lymphoma, including autoimmune hemolytic anemia and immune thrombocytopenic purpura. The concurrent diagnoses of Hodgkin lymphoma and acquired aplastic anemia, however, is extremely rare. We report a 56-year-old Japanese female patient with severe aplastic anemia and increased large granular lymphocytes prior to the recurrence of Hodgkin lymphoma. After being in remission for 10 years from Hodgkin lymphoma, she developed progressive pancytopenia. The large granular lymphocytes (expressed CD3+ CD8+ TCRαβ+) had a polyclonal distribution, the serum-soluble FasL concentration was significantly elevated, and bone marrow biopsy showed severely hypocellular bone marrow without infiltration of abnormal lymphocytes. No lymphadenopathy was observed that would suggest a relapse of Hodgkin lymphoma. A diagnosis of aplastic anemia was made, and treatment with corticosteroids and cyclosporine was initiated. Two months later, she suddenly developed celiac and mediastinal lymphadenopathy. She underwent one cycle of chemotherapy before she died of progressive pancytopenia. Autopsy revealed the recurrence of Hodgkin lymphoma, nodular sclerosis in the lymph nodes and markedly hypocellular bone marrow. Although autoimmune disorders are described in Hodgkin lymphoma, our case shows a rare instance of a patient who had aplastic anemia as the first manifestation of a relapse of Hodgkin lymphoma.