Aggressive chemotherapy in adult primary myelodysplastic syndromes

Summary Twenty-nine adult patients with primary myelodysplastic syndromes (MDS) and an excess of marrow blasts were treated by aggressive chemotherapy while still in MDS phase (20 cases) or after progression to ANLL (9 cases). Median age was 47.5 (range 18–68). Twenty-eight patients received a combination of Rubidazone and Ara C and 1 received High dose Ara C. Fourteen patients (48%) achieved complete remission (CR), 5 (17%) were treatment failures (F) and 10 (35%) died during therapy induced aplasia (DA). Median disease free survival was 8.5 months. Median survival of the whole population was 6 months from the onset of treatment, and 17 months in patients achieving CR. These results were significantly less favorable than those obtained at our institution in de novo ANLL with the same chemotherapy regimens. No statistically significant prognostic factors of treatment outcome emerged but patients with normal cytogenetic findings seemed to have both a higher CR rate and longer remissions than patients with abnormal karyotypes. Patients under 50 did not have higher CR rates than older patients, although they had longer remissions (with 3 out of 6 CRs exceeding 2 years). Finally, treatment outcome and survival were identical in patients treated in the MDS phase and in those treated after progression to ANLL. Combination chemotherapy is a highly toxic approach in MDS and essentially seems to benefit younger patients with a normal karyotype, in whom some long remissions can be obtained.     

Prognosis of patients with del(5q) MDS and complex karyotype and the possible role of lenalidomide in this patient subgroup

The survival of patients with myelodysplastic syndromes is strongly affected by chromosomal abnormalities. Patients with an isolated del(5q31) have a favourable prognosis that worsens with the addition of another chromosomal abnormality. It has been reported that both patients with isolated del(5q31) and those with one single additional chromosomal abnormality achieve hematological and cytogenetic remissions with lenalidomide therapy. Whether this translates into improved overall survival of the patient population is unclear. We analysed data of 25 patients with myelodysplastic syndrome and complex chromosomal abnormalities including del(5q31) and show that their median survival is between 7 and 8 months, irrespective of the medullary blast count. Furthermore, we present data of a patient with complex karyotypic anomalies inclusive of del(5q31) treated with lenalidomide who achieved complete cytogenetic remission. This cytogenetic remission was diagnosed after 6 months, and the hematological response is ongoing at 9 months of therapy at a dose of 5 mg p.o. daily. We conclude that lenalidomide has the potential to induce sustained hematological and cytogenetic remissions in the poor prognosis MDS subgroup of del(5q31) patients with complex chromosomal anomalies and that this is likely to improve overall survival.     

New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients

We have generated a large, unique database that includes morphologic, clinical, cytogenetic, and follow-up data from 2124 patients with myelodysplastic syndromes (MDSs) at 4 institutions in Austria and 4 in Germany. Cytogenetic analyses were successfully performed in 2072 (97.6%) patients, revealing clonal abnormalities in 1084 (52.3%) patients. Numeric and structural chromosomal abnormalities were documented for each patient and subdivided further according to the number of additional abnormalities. Thus, 684 different cytogenetic categories were identified. The impact of the karyotype on the natural course of the disease was studied in 1286 patients treated with supportive care only. Median survival was 53.4 months for patients with normal karyotypes (n = 612) and 8.7 months for those with complex anomalies (n = 166). A total of 13 rare abnormalities were identified with good (+1/+1q, t(1q), t(7q), del(9q), del(12p), chromosome 15 anomalies, t(17q), monosomy 21, trisomy 21, and -X), intermediate (del(11q), chromosome 19 anomalies), or poor (t(5q)) prognostic impact, respectively. The prognostic relevance of additional abnormalities varied considerably depending on the chromosomes affected. For all World Health Organization (WHO) and French-American-British (FAB) classification system subtypes, the karyotype provided additional prognostic information. Our analyses offer new insights into the prognostic significance of rare chromosomal abnormalities and specific karyotypic combinations in MDS.     

Prognostic implications of morphology and karyotype in primary myelodysplastic syndromes

Forty-nine patients with primary myelodysplastic syndromes (MDS) were subclassified according to French-American-British (FAB) Cooperative Group criteria. Eight patients had acquired idiopathic sideroblastic anemia (AISA), ten had chronic myelomonocytic leukemia (CMMoL), 14 had refractory anemia (RA), nine had refractory anemia with excess blasts (RAEB), and five had refractory anemia with excess blasts in transformation (RAEB-T); three patients could not be subclassified. The actuarial median survival for patients with AISA or with RA had not been reached at 60 months of follow-up. The median survival times for patients with CMMoL, RAEB, and RAEB-T were 25, 21, and 16 months, respectively. The percentages of patients with each subtype who developed ANLL were none in AISA, 20% in CMMoL, 7% in RA, 56% in RAEB, and 40% in RAEB-T. Patients with CMMoL had a poor prognosis independent of transformation to acute nonlymphocytic leukemia (ANLL), whereas patients with RAEB and RAEB-T had a high incidence of transformation and short survival times. Clonal chromosomal abnormalities were present in bone marrow cells from 19 patients at the time of diagnosis, and two others developed an abnormal karyotype at the time of leukemic transformation. The most frequent abnormalities, including initial and evolutionary changes, were trisomy 8 (9 patients), deletion of 5q (4 patients), and deletion of 20q (4 patients). The median survival times were 32 months for patients with an abnormal karyotype, and 48 months for those with a normal karyotype (P = 0.2). Specific chromosomal abnormalities were not associated with particular histologic subtypes; however, a high percentage of patients with RAEB and RAEB-T had an abnormal clone (89% and 80%, respectively). The percentages of patients with clonal abnormalities were 13% for AISA, 20% for CMMoL, and 29% for RA. The MDS transformed to ANLL in 42% of patients with an abnormal karyotype, compared to 10% of those with an initially normal karyotype (P less than .01). Among patients with RA, RAEB, and RAEB-T, the risk of leukemic transformation was confined to those with an abnormal karyotype (P less than .01). Thus, in the present study, morphology and karyotype combined were the best indicators of outcome in patients with MDS.     

Prognostic value of trisomy 8 in primary myelodysplastic syndrome

Background: According to the International Prognostic Scoring System (IPSS), sole +8 is categorized as intermediate cytogenetic subgroup. But as some myelodysplastic syndrome (MDS) patients with +8 perhaps progress quickly to acute leukaemia and have shorter survival, some reports have suggested that +8 should be categorized into poor risk cytogenetic group. The aim of this study was to clarify the prognostic role of +8 in MDS patients by comparing patients with normal karyotype, 20q‐ and ‐7/7q‐. Methods: The consecutive samples of 435 MDS patients in Shanghai were collected by prospective methods and diagnosed according to World Health Organization classification. Cytogenetic analysis was performed using conventional G‐banding karyotyping and fluorescence in situ hybridization techniques. Prognosis was estimated by univariate Log‐rank method and multivariate Cox proportional hazard models. Results: Of 424 cases completing the cytogenetic analysis, 71 (16.7%) had +8, including 38 patients with sole +8 (9.0%). No significant difference in median survival was observed between patients with sole +8 and that with +8 and one of other abnormalities. The +8 clone size was not linked to survival. The median survival of patients with +8, normal karyotype and complex karyotype was 25 months, 38.1 months and 5.9 months respectively. However, no significant difference was observed between patients with 20q‐ (21.4 months) and ‐7/7q‐ (25.8 months). Trisomy 8 was an independent prognostic factor by Cox regression model. Conclusion: There is no significant difference in prognosis between patients with +8 and patients with 20q‐ or ‐7/7q‐. Trisomy 8, 20q‐ and ‐7/7q‐ are categorized as intermediate cytogenetic risk according to our primary study.     

Cytogenetic findings in 179 patients with myelodysplastic syndromes

Cytogenetic analyses were performed on 266 bone marrow and peripheral blood samples from 179 patients with myelodysplastic syndromes (MDS). According to the FAB classification, 42 patients presented with RA, 18 with RARS, 37 with RAEB, 22 with CMML, and 29 with RAEB-T. Nine patients showed a secondary MDS (S MDS). FAB classification was not available for 22 patients. Clonal karyotype anomalies were found in 92 patients (51.4%). Complex chromosome abnormalities occurred in 17 (18.5%) of them. An evolution of the karyotype was detected in 16 cases (17.4%). Cytogenetically independent cells or cell clones were found in eight patients. Nonclonal chromosome abnormalities were uncovered in 29 (16.2%) of the 179 MDS patients. Consecutive studies were performed in 48 patients and revealed a good correlation of initial karyotype and clinical course. The most frequent single anomalies were 5q- in 29 (31.5%), –7 in 22 (23.9%), trisomy 1q in 14 (15.2%), and +8 in 13 (14.1%) of 92 patients respectively. Our cytogenetic findings are presented in detail and discussed in relation to patients' age, morphological classification, clinical course, and prognostic impact. The contribution of cytogenetic findings to the delineation of multistep pathogenesis of MDS with special emphasis to karyotype instability is demonstrated.     

急性红白血病55例染色体特征和预后分析

目的探讨急性红白血病（M6）染色体特征和预后因素。方法回顾性分析55例患者染色体核型特征,采用病例对照方法,分为原发组和骨髓增生异常综合征（MDS）转化组;染色体核型异常组和正常组,并分析各组异基因造血干细胞移植（all-HSCT）治疗和（或）化疗疗效及生存预后因素。结果45例经染色体检查,18例正常,染色体异常检出率为60．0％（27／45）,其中复杂异常17例,简单异常10例,10例可见亚二倍体或超二倍体明显增多,18．5％（5／27）5号染色体受累,25．9％（7／27）7号或8号染色体受累。55例患者完全缓解（CR）率63．6％;MDS转化组CR率（42．8％）显著低于原发组（85．2％）,P〈0．05;染色体核型异常组CR率（37．0％）显著低于正常组（83．3％）,P〈0．01。生存预后因素：随访中位时间30（3—79）个月,染色体核型异常组和MDS转化M6患者生存期（OS）和无病生存期（DFS）,移植治疗者较化疗者显著延长（P〈0．01）。16例患者行all-HSCT治疗,其中9例为染色体核型异常MDS转化M6患者,4例为未缓解患者;移植后11例DFS 28个月,2年生存率68．7％（11／16）。结论染色体核型异常和（或）MDS转化M6患者常规化疗疗效差、生存期短,预后差,all-HSCT治疗显著延长生存期,改善预后,染色体核型异常和（或）MDS转化M6患者,宜早期all-HSCT治疗。     

Molecular characterization of chromosome 7 long arm deletions in myeloid disorders

Partial deletion of the long arm of chromosome 7 is a common abnormality in the bone marrow cells of patients with myelodysplastic syndrome (MDS) or acute nonlymphocytic leukemia (ANLL). This study was undertaken to characterize the chromosome breakpoints in molecular terms and to determine if hemizygosity or submicroscopic deletions occur in patients without any cytogenetically detectable abnormality of chromosome 7. We studied restriction fragment length polymorphisms with 10 chromosome 7-specific DNA probes in separated WBC fractions. No molecular abnormalities occurred in lymphocyte-derived DNA. Several probes located in band 7q22 or distally thereof detected deletion of one allele in granulocyte-derived DNA from all four patients with chromosome 7 long arm deletion. In the granulocytes of one patient heterozygosity for the T cell receptor beta chain gene (in band 7q35) indicated that the deletion was interstitial. NJ-3, a proalpha2(I)collagen gene probe (in band 7q21-22) detected heterozygosity in the granulocytes of one patient. No hemizygosity or deletions were found in four patients with two normal chromosomes 7. These results confirm that mature granulocytes but not lymphocytes are derived from the abnormal clone. Interstitial deletions exist, and the extent of deleted genomic material varies among patients.     

Haploinsufficiency of RPS14 in 5q- syndrome is associated with deregulation of ribosomal- and translation-related genes

We have previously demonstrated haploinsufficiency of the ribosomal gene RPS14 , which is required for the maturation of 40S ribosomal subunits and maps to the commonly deleted region, in the 5q− syndrome. Patients with Diamond-Blackfan anaemia (DBA) show haploinsufficiency of the closely related ribosomal protein RPS19, and show a consequent downregulation of multiple ribosomal- and translation-related genes. By analogy with DBA, we have investigated the expression profiles of a large group of ribosomal- and translation-related genes in the CD34⁺ cells of 15 myelodysplastic syndrome (MDS) patients with 5q− syndrome, 18 MDS patients with refractory anaemia (RA) and a normal karyotype, and 17 healthy controls. In this three-way comparison, 55 of 579 ribosomal- and translation-related probe sets were found to be significantly differentially expressed, with approximately 90% of these showing lower expression levels in the 5q− syndrome patient group. Using hierarchical clustering, patients with the 5q− syndrome could be separated both from other patients with RA and healthy controls solely on the basis of the deregulated expression of ribosomal- and translation-related genes. Patients with the 5q− syndrome have a defect in the expression of genes involved in ribosome biogenesis and in the control of translation, suggesting that the 5q− syndrome represents a disorder of aberrant ribosome biogenesis.     

Correlations between cytogenetics and morphology in myelodysplastic syndromes

Summary In order to detect possible relationships between cytogenetic abnormalities and morphologic features in myelodysplastic syndromes (MDS), 48 patients with MDS were investigated. Clonal cytogenetic abnormalities were present in bone marrow cells from 27 patients (56%). The most frequent single anomaly was del (5 q) (10 cases), followed by monosomy 7 (3 cases), trisomy 8 (3 cases) and del (20 q) (2 cases). Complex anomalies were present in 6 patients. Morphologically, according to the French-American-British (FAB) classification: 17 cases were considered as refractory anemia (RA), 17 as RA with excess of blasts (RAEB), 2 as RAEB in transformation, 2 as acquired idiopathic sideroblastic anemia and 10 as chronic myelomonocytic leukemia. With regard to the FAB classification, del (5 q) was often associated with RA and complex cytogenetic anomalies with RAEB. When myelodysplasia was studied in individual myeloid lineages, del (5 q) was associated with hypolobulated megakaryocytes, monosomy 7 with micromegakaryocytes and complex chromosomal anomalies with the association of two or more features of dysmegakaryocytopoiesis. Del (11 q) was associated with increased iron storage and del (20 q) with marked dyserythropoiesis. No correlation was observed between cytogenetic anomalies and features of dysgranulocytopoiesis.     

Acute erythroleukemia with t(3;5) accompanied by hepatocellular carcinoma.

A female patient in whom acute nonlymphocytic leukemia (ANLL, FAB-M6) developed during treatment of hepatocellular carcinoma (HCC) is described. Two years after partial hepatectomy and subsequent chemotherapy, leukemia developed following a 2 month preleukemic stage. Chromosomal analysis revealed an abnormal karyotype, 46,XX,-5, + der(5)t(3;5)(q25;q31). The balanced translocation t(3;5) has been observed in all types of ANLL and MDS except for ANLL M3 subtype. We summarize patients with ANLL M6 and t(3;5).     

骨髓增生异常综合征克隆性8号染色体三体和7号染色体缺失的发生及其临床意义

目的：了解＋8和-7／7q-克隆在骨髓增生异常综合征（MDS）中的发生情况，探讨＋8和-7／7q-克隆在MDS发生发展中的可能机制及其临床意义。方法：采用短期培养法和G显带技术，对MDS患者的染色体异常、尤其＋8和-7／7q～核型进行分析。结果：70例原发性MDS患者中，有43例存在染色体异常，异常检出率为61．4％，最常见的染色体异常为＋8（18例）和-7／7q-（8例），其中4例为＋8与-7／7q-并存。＋8克隆多出现在RA阶段，而-7／7q-克隆则出现在疾病进展中。伴有-7／7q-核型的MDS，更容易转化为白血病。结论：＋8和-7／7q-核型仍是MDS最为常见的染色体异常。＋8克隆出现在MDS的早期，可能与Fas介导的细胞凋亡有关；而-7／7q-克隆的形成，导致MDS的进展及向白血病转化，可能与丢失片段的抑癌基因的失活有关。     

Clinical effects of low-dose Ara-C in acute nonlymphocytic leukemia and myelodysplastic syndromes

Forty-eight patients with acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndromes (MDS) were treated with low-dose Ara-C regimen (LDAC) (10 mg/m2 or 10 mg/body subcutaneously every 12 hours). Complete remission (CR) was obtained in sixteen patients (33%) and partial remission (PR) in six (16%). Seven of eight patients with hypoplastic leukemia entered CR. However, LDAC was not effective in MDS and ANLL developing from MDS. The rate of CR was 20% in relapsed or refractory ANLL. Relapse was occurred in thirteen patients until now. The median duration of remission was 7 months (range: 3-20 months). Seven of the sixteen patients who achieved CR were received LDAC at the same dose for 10 days every month as a maintenance therapy. The duration of CR of these patients was shown to be longer than that of the patients without any maintenance therapy. Myelosuppression was observed in nearly all of them and the other clinical findings including cytogenetic analysis indicated cytotoxicity rather than differentiation as the mechanism of LDAC. LDAC was effective especially in hypoplastic leukemia and the maintenance therapy was found to prolong the duration of CR.     

The impact of cytogenetic abnormalities on the prognosis of primary myelofibrosis: a prospective survey of 202 cases in Japan

Cytogenetic abnormalities were often observed in primary myelofibrosis patients. The presence of specific cytogenetic abnormalities, such as sole abnormalities of chromosome 13q?, 20q?, or ?7/7q?, is reported to have the influence on the prognosis of primary myelofibrosis. We analyzed the data from the prospective survey of Japanese primary myelofibrosis patients which was conducted from 1999 to clarify the impact of cytogenetic abnormalities on the prognosis of primary myelofibrosis. A total of 202 primary myelofibrosis patients had the cytogenetic and the prognostic data. Eighty (40%) out of 202 cases had cytogenetic abnormalities, and an association was evident for platelet counts. Although the presence of an abnormal karyotype did not affect the prognosis, primary myelofibrosis patients with cytogenetic abnormalities other than 13q? and 20q? showed an inferior prognosis compared to patients with a normal karyotype or sole 13q? or 20q? abnormalities. Patients with an unfavorable cytogenetic profile (abnormal cytogenetics other than 13q? or 20q?) also had a greater tendency to transform to leukemia than patients with a favorable cytogenetic profile (normal cytogenetics, sole abnormalities of either chromosome 13q?, or 20q?). Abnormal cytogenetics other than 13q? or 20q? in primary myelofibrosis patients has the poor prognostic effect for both survival and the risk of leukemic transformation.     

Two Independent Clones in Myelodysplastic Syndrome Following Treatment of Acute Myeloid Leukemia

We describe a 55-year-old Japanese woman with therapy-related myelodysplastic syndrome (t-MDS) with 2 independent clones, t(1;2)(p36;p21) and t(11;12)(pl5;ql3). She was diagnosed with acute myeloid leukemia (AML) with cytological features of the bone marrow and peripheral blood. Cytogenetic evaluation revealed a 46,XX karyotype. She received chemotherapy and achieved complete remission (CR). Despite maintenance chemotherapy, she suffered a relapse. Chromosomal analysis showed t(1;2)(p36;p21) in 2 of 20 metaphases. At second CR, this clone transiently disappeared. Nine months later, t(1;2) (p36;p21) was detected again in 3 of 20 metaphases while the patient remained in CR. Six months later, bone marrow examination disclosed trilineage dysplasia without an excess of blasts, suggesting MDS. t(1;2)(p36;p21) was observed in 16 of 20 metaphases. The clinical course and serial cytogenetic findings were diagnostic of t-MDS. The duration of t-MDS was 6 years. During this period, persistent t(1;2)(p36;p21) and transient t(11;12)(p15;q13) were found. When t-MDS evolved toAML, cytogenetic evaluation revealed 46,XX,t(1;2)(p36;p21),del(7)(q22),add(19)(p13).     

Secondary clonal cytogenetic abnormalities following successful treatment of acute promyelocytic leukemia

To identify patients who developed secondary clonal cytogenetic aberrations (CCA) following therapy for acute promyelocytic leukemia (APL), we retrospectively analyzed cytogenetic results from 123 patients diagnosed with APL between 1995 and 2007, who had ongoing cytogenetic analysis undertaken in our laboratory. During follow‐up for APL we identified 12 patients (9.8%) who developed CCA, not detected at diagnosis of APL and unrelated to their original APL karyotype. All patients had received all‐trans retinoic acid (ATRA) and chemotherapy and were in complete remission for APL when secondary CCA were identified. The median latency period between diagnosis of APL and emergence of secondary CCA was 27.5 months (range: 2–54 months). To date, four patients with CCA have been diagnosed with therapy‐related myelodysplastic syndrome (t‐MDS)/acute myeloid leukemia (t‐AML), giving a median t‐MDS/AML free survival of 78 months, with follow‐up ranging between 20 and 136 months from APL diagnosis. Three patients have died: two patients died of t‐AML and another developed relapsed APL with persistence of his secondary clone but no diagnosis of t‐MDS/AML and died from transplant‐related complications. Two patients are alive with t‐MDS. Seven patients with CCA are alive with no morphological evidence of MDS at the time of their last known follow‐up; thus median survival has not been reached. The appearance of these abnormalities in the absence of morphological evidence of MDS in the majority of patients is unusual, and highlights the importance of continued cytogenetic follow‐up in these patients. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.     

The impact of concomitant cytogenetic abnormalities on acute myeloid leukemia with monosomy 7 or deletion 7q after HLA-matched allogeneic stem cell transplantation

Monosomy 7 or deletion 7q (-7/7q-) is the most frequent adverse cytogenetic features reported in acute myeloid leukemia (AML), and is a common indication for allogeneic stem cell transplantation (SCT). Nevertheless, -7/7q- occurs frequently with other high-risk cytogenetic abnormalities such as complex karyotype (CK), monosomal karyotype (MK), monosomy 5 or deletion 5q (-5/5q-), 17p abnormalities (abn(17p)) or inversion of chromosome 3 (inv(3)), the presence of which may influence the outcomes after SCT. A total of 1109 patients were allocated to this study. Two-year probability of leukemia-free survival (LFS) and overall survival (OS) were 30% and 36%, respectively. Two-year probability of non-relapse mortality (NRM) was 20%. We defined five different cytogenetic subgroups: the “-7/7q- ± CK group- designated group1,” the “MK group-designated group 2,” the “-5/5q- group- designated group 3,” the “abn(17p) group- designated group 4” and the “inv(3) group- designated group 5.” The 2-year probability of LFS in first remission was 48% for group 1, 36.4% for group 2, 28.4% for group 3, 19.1% for group 4 and 17.3% for group 5, respectively (P < .001). Multivariate analysis confirmed those significant differences across groups. Note, SCT in -7/7q- AML provides durable responses in one third of the patients. The presence of -7/7q- with or without CK in the absence of MK, abn(17p) or inv(3) is associated with a better survival after SCT. On the contrary, addition of MK, -5/5q-, abn(17p) or inv(3) identifies a sub-group of patients with poor prognosis even after SCT.     

Cytogenetic features in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) comprise a group of bone marrow diseases characterized by profound heterogeneity in morphologic presentation, clinical course, and cytogenetic features. Roughly 50% of patients display clonal chromosome abnormalities. In several multicentric studies, the karyotype turned out to be one of the most important prognostic parameters and was incorporated into statistical models aiming for a better prediction of the individual prognosis like the International Prognostic Scoring System. However, due to the profound cytogenetic heterogeneity, the impact of many rare abnormalities as well as combinations of anomalies occurring in a substantial portion of patients with MDS is still unknown and can only be delineated on the basis of large international multicentric cooperations. Recently, the German–Austrian MDS Study Group presented cytogenetic findings in 2,072 patients with MDS, which serve as a basis for the characterization of the cytogenetic subgroups discussed in this article. The availability of new therapeutic options for low- and high-risk MDS targeted against distinct entities characterized by specific chromosome abnormalities, like 5q-deletions, monosomy 7, and complex abnormalities underlines the important role of cytogenetics for the clinical management of MDS. This article thus focuses on the clinical and prognostic relevance, the molecular background, and therapeutic perspectives in these three cytogenetic subgroups.     

Agranular CD4+CD56+ blastic natural killer leukemia/lymphoma

Blastic natural killer cell leukemia/lymphoma (blastic NKL/L) is characterized by blastic morphology and a distinctive immunophenotype combining blastic features and cytologically resembling acute myeloid or lymphoid leukemia. The clinical, pathologic, and cytogenetic features of blastic NKL/L have not yet been systematically identified. We report herein a case of blastic NKL/L with skin lesion, adenopathy, and systemic lymphoadenopathy. The identified tumor cells were positive for CD4 and CD56, and negative for T-cell, B-cell, and myeloid markers. T-cell receptor beta, gamma, delta, and immunoglobulin heavy chain genes in the bone marrow cells showed germ-line configurations. Southern blot analysis with a terminal probe did not reveal any Epstein-Barr virus infection. Although patients diagnosed as blastic NKL/L have generally shown chemotherapy resistance and poor prognosis, our patient was treated with a combined chemotherapy, which is also used for acute lymphoblastic leukemia, and has maintained complete remission (CR) for more than 13 months. In addition to clinical investigations, we thoroughly analyzed his karyotype by using a combination of G-banding and a new technique, spectral karyotyping. The karyotype was described as 45, XY, der(1)t(1;20)(p32;q11.2), der(6) (1pter-->1p32:: 6p21.1-->6q13:: 7q11.2-->7qter), der(7) t(7;20)(q11.2;q11.2), t(13;14)(q14;q32), der(13)t(6;13) (p21.1; q14), -20.