Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia

We describe the clinical and laboratory findings of 78 adult patients with T-prolymphocytic leukemia (T-PLL) studied over the last 12 years. The main disease features were splenomegaly (73%), lymphadenopathy (53%), hepatomegaly (40%), skin lesions (27%), and a high leukocyte count (greater than 100 x 10(9)/L in 75%) with nucleolated prolymphocytes. A variant form with small, less typical cells was recognized in 19%. Membrane markers defined a postthymic phenotype TdT- , CD2+, CD3+, CD5+, CD7+; in 65%, the cells were CD4+ CD8-, in 21%, they coexpressed CD4 and CD8, and, in 13%, they were CD4- CD8+. Serology for human T-cell leukemia/lymphoma virus Type-I (HTLV-I) was negative in the 27 cases investigated. Cytogenetic analysis in 30 cases showed a consistent abnormality of chromosome 14, usually inv (14), with breakpoints at q11 and q32 in 76% of cases. Trisomy 8, including iso8q, was shown in 53%; t (11;14)(q13;q32) was documented in one case; and one had a normal karyotype. The clinical course was progressive with a median survival of 7.5 months. Thirty-one patients were treated with 2′ deoxycoformycin and 15 responded (3 complete remissions and 12 partial remissions); the response rate (48%) increased to 58% in patients with a CD4+ CD8- phenotype. The median survival of responders was 16 months and of nonresponders 10 months; other treatments were less effective. T-PLL is a distinct clinico-pathologic entity with aggressive course and characteristic chromosome abnormalities. A subgroup of patients may benefit from deoxycoformycin.

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Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia

Blood ◽

10.1182/blood.v78.12.3269.3269 ◽

1991 ◽

Vol 78 (12) ◽

pp. 3269-3274 ◽

Cited By ~ 318

Author(s):

E Matutes ◽

V Brito-Babapulle ◽

J Swansbury ◽

J Ellis ◽

R Morilla ◽

...

Keyword(s):

Median Survival ◽

Normal Karyotype ◽

Skin Lesions ◽

Variant Form ◽

Type I ◽

Chromosome 14 ◽

Trisomy 8 ◽

Laboratory Findings ◽

Prolymphocytic Leukemia ◽

Human T Cell

Abstract We describe the clinical and laboratory findings of 78 adult patients with T-prolymphocytic leukemia (T-PLL) studied over the last 12 years. The main disease features were splenomegaly (73%), lymphadenopathy (53%), hepatomegaly (40%), skin lesions (27%), and a high leukocyte count (greater than 100 x 10(9)/L in 75%) with nucleolated prolymphocytes. A variant form with small, less typical cells was recognized in 19%. Membrane markers defined a postthymic phenotype TdT- , CD2+, CD3+, CD5+, CD7+; in 65%, the cells were CD4+ CD8-, in 21%, they coexpressed CD4 and CD8, and, in 13%, they were CD4- CD8+. Serology for human T-cell leukemia/lymphoma virus Type-I (HTLV-I) was negative in the 27 cases investigated. Cytogenetic analysis in 30 cases showed a consistent abnormality of chromosome 14, usually inv (14), with breakpoints at q11 and q32 in 76% of cases. Trisomy 8, including iso8q, was shown in 53%; t (11;14)(q13;q32) was documented in one case; and one had a normal karyotype. The clinical course was progressive with a median survival of 7.5 months. Thirty-one patients were treated with 2′ deoxycoformycin and 15 responded (3 complete remissions and 12 partial remissions); the response rate (48%) increased to 58% in patients with a CD4+ CD8- phenotype. The median survival of responders was 16 months and of nonresponders 10 months; other treatments were less effective. T-PLL is a distinct clinico-pathologic entity with aggressive course and characteristic chromosome abnormalities. A subgroup of patients may benefit from deoxycoformycin.

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Adult T-cell leukemia/lymphoma: report of two cases

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822008000300012 ◽

2008 ◽

Vol 41 (3) ◽

pp. 288-292 ◽

Cited By ~ 4

Author(s):

Ricardo Aparecido Olivo ◽

Fabrício Frederico Mendes Martins ◽

Sheila Soares ◽

Helio Moraes-Souza

Keyword(s):

T Cell ◽

Clinical Laboratory ◽

Skin Lesions ◽

Type I ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Laboratory Findings ◽

Adult T Cell Leukemia ◽

Human T Cell ◽

Disease Case

Adult T-cell leukemia/lymphoma is a lymphoproliferative disorder of mature T lymphocytes associated with infection with human T-cell lymphotrophic virus type I (HTLV-I). Adult T-cell leukemia/lymphoma is characterized by clinical and laboratory polymorphism that allows it to be classified into four distinct subgroups: smoldering, chronic, acute and lymphomatous types. We present here two cases of adult T-cell leukemia/lymphoma, respectively in the acute and lymphomatous forms of the disease. Case 1 was a 35-year-old woman who presented abdominal distension accompanied by hepatosplenomegaly, adenomegaly, skin lesions, positivity for anti-HTLV-I antibodies and leukocytosis with the presence of flower cells. Case 2 was a 38-year-old man who was admitted with generalized lymphadenomegaly, positivity for anti-HTLV-I antibodies, hypercalcemia and osteolytic lesions. In this paper, we correlate the clinical-laboratory findings of these two cases with data in the literature.

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Prognostic implications of morphology and karyotype in primary myelodysplastic syndromes

Blood ◽

10.1182/blood.v67.6.1765.1765 ◽

1986 ◽

Vol 67 (6) ◽

pp. 1765-1772 ◽

Cited By ~ 193

Author(s):

RH Jacobs ◽

MA Cornbleet ◽

JW Vardiman ◽

RA Larson ◽

MM Le Beau ◽

...

Keyword(s):

Median Survival ◽

Myelodysplastic Syndromes ◽

Chromosomal Abnormalities ◽

Bone Marrow Cells ◽

Normal Karyotype ◽

Refractory Anemia ◽

Survival Times ◽

Trisomy 8 ◽

Leukemic Transformation ◽

Abnormal Karyotype

Abstract 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.

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The Number of Cooperating Mutations in AML Is Still Growing: A Study on 3789 Patients.

Blood ◽

10.1182/blood.v108.11.801.801 ◽

2006 ◽

Vol 108 (11) ◽

pp. 801-801 ◽

Cited By ~ 1

Author(s):

Susanne Schnittger ◽

Claudia Schoch ◽

Ulrike Bacher ◽

Frank Dicker ◽

Wolfgang Kern ◽

...

Keyword(s):

Tyrosine Kinases ◽

Normal Karyotype ◽

Genetic Alterations ◽

Trisomy 13 ◽

Type I ◽

Type Ii ◽

Loss Of Function ◽

Trisomy 8 ◽

Reciprocal Translocations ◽

Diagnosis And Prognosis

Abstract According to a two hit model in AML at least two genetic alterations are required for the clinical manifestation of leukemia. Many recent studies have shown that one type comprizes genetic hits causing a stop in differentiation. In most cases these are loss of function mutations in transcription factors, e.g. through reciprocal translocations like AML1TO, CBFBMYH11, and PML-RARA or molecular mutations in CEBPA and AML1. Others are mutations in nuclear transport proteins like NPM1 or NUP214 (DEK). This type of mutations is reflected mainly in the morphologic phenotype of the AML and is called type II mutation. The other type of mutations (type I mutations) usually leads to enhanced proliferation and mostly comprizes activating mutations in genes coding for tyrosine kinases or molecules downstream of the respective pathways. These two kind of mutations often are referred to as cooperating mutations. Based on our molecular analyses of 3789 AML we found that the pattern in which these mutations occur is not random and that certain type I mutations prefer to occur together with certain type II mutations. This suggests that certain combinations may have optimal cooperative functions. Combinations of two type I mutations are very rare and type II mutations occur completely mutually exclusive. The following preferential combinations of type I mutations with chromosomal aberrations were found (significant associations are given in the table): FLT3-LM with t(15;17), t(6;9) and normal karyotype; FLT3-TKD with normal karyotype; NRAS with inv(16)/t(16;16) and inv(3)/t(3;3); KITD816 with t(8;21); KITexon11 with inv(16)(t(16;16). Newly detected was the association of JAK2V617F with trisomy 8, suggesting that on #8 a still unknown type I mutation may be located. In addition JAK2 was correlated with t-AML with t(8;21). Furtheron mutations in the TKD domain of VEGFR1 were associated with mutated AML1 and trisomy 13. In addition, some of the type I mutations were correlated to normal karyotypes and were associated with other molecular mutations: FLT3-LM is preferentially found in AML with MLL-PTD as well as in AML with NPM1-, CEBPA-, and AML1-mutations. For some combinations a prognostic relevance already was shown: FLT3-LM has unfavourable impact on EFS in normal karyotype (p=0.04) and on OS in t(15;17) (p=0.05), in CEBPA mutated AML (p=0.03) and even completely abrogates the favourable impact of NPM1 (p<0.001). KITD816 mutations were shown to confer an extreme bad impact on OS in t(8;21) (p<0.001). In contrast, NRAS seems associated with an improved outcome in cases in which all unfavourable molecular markers are negative (p=0.06). In conclusion this study supports the growing importance of molecular characterization of AML with respect to diagnosis and prognosis. Coincidience of type I and II mutations Type I (row), Type 2 (column) FLT3-LM (%) NRAS (%) KITD816 (%) KITexon8 (%) JAK2 (%) VEGFR1 (%) For clarity only significantly elevated frequencies are shown in comparison to overall frequencies in AML. Percentages of cases with type I alterations within the groups of type II are given. Prognostically favourable associations coded as #, unfavourable associations coded as * total 23.4 10.3 1.7 < 1 6.2 n.a. t(15;17) 35.3* t(8;21) 10.5* 9.5 t(rare;21) 75 inv(16)/t(16;16) 37.6# 10.8 inv(3)/t(3;3) 26.8 t(6;9) 75 MLL-PTD 35.2 CEBPA 36* AML1 18 14.2 NPM1 40* Trisomy 8; unknown gene 23.3

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Multivariate Evaluation of the Prognostic and Therapeutic Relevance of Cytogenetics in a Merged European-American Cohort of 3860 Patients with MDS.

Blood ◽

10.1182/blood.v110.11.247.247 ◽

2007 ◽

Vol 110 (11) ◽

pp. 247-247 ◽

Cited By ~ 4

Author(s):

Detlef Haase ◽

Elihu H. Estey ◽

Christian Steidl ◽

Ulrich Germing ◽

Guillermo Garcia-Manero ◽

...

Keyword(s):

Supportive Care ◽

Median Survival ◽

Survival Data ◽

De Novo ◽

Normal Karyotype ◽

Epigenetic Therapy ◽

Chemotherapy Response ◽

Trisomy 8 ◽

Therapy Regimen ◽

Secondary Mds

Abstract This study investigated the influence of cytogenetic findings on survival in MDS, after accounting for other known prognostic parameters and type of treatment. We identified 3210 patients with a known therapy regimen from our large database, including 3860 patients with MDS and secondary AML following MDS. This data pool was collected in the framework of a cooperative project merging data from the German-Austrian MDS study group (55% of pts.) and the MD Anderson Cancer Centre (MDA), Houston, USA (45% of pts.). Median age of all study patients was 65.9 years, the female-male ratio 1:1.53. After accounting for age, sex, % marrow blasts, de novo vs. primary MDS, treatment (supportive care, AML-type, and epigenetic therapy) and site of treatment(Germany/Austria vs.MDA) we looked at the effect of cytogenetic subgroups on survival. Survival data was available for 95.8% of all pts. The distribution of main cytogenetic categories was as follows: normal (1.727, 45%), 5q- (208, 5%), 5q- +1 abnormality (73, 2%), −7/7q- not complex (222, 6%), +8 not complex (203, 5%), complex with −5/−7 (627, 17%), other complex (195, 5%), 20q- not complex (69, 2%), and other not complex (475, 13%). Chemotherapy (c) was applied in 32.9% while 67.1% were treated with supportive care (sc) or epigenetic therapy. The cytogenetic prognosis according to IPSS-criteria was favourable in 1704 (53.1%) and unfavourable in 839 (26.13%) of the 3210 study patients. Multivariate analysis revealed the following non-cytogenetic parameters as unfavourable: age >60, male sex, blasts >5%, secondary MDS, AML-like chemotherapy, MDA as site (due to overrepresentation of high risk MDS). After accounting for these variables the following relative Hazard ratios (HR of 1.0 for normal karyotype) were calculated allowing a relative ranking of cytogentic findings: 5q-: 0.93, 5q- +1: 1.06, other not complex: 1.11, 20q-: 1.31, +8: 1.65, complex without −5/−7: 1.76 −7/7q-: 2.09, complex with −5/−7: 3.88. The effect of cytogenetics in pts. with either supportive care (sc) or chemotherapy (c) measured as relative HR (see above) were: 20q- (sc: 1.25, c: 1.51), 5q- (sc: 0.93, c: 0.73), other not complex (sc: 1.07, c: 1.04), −7/7q- (sc: 2.10, c: 2.09), +8 (sc: 2.05, c:1.54), complex without −5/−7 (sc: 2.23, c: 1.75), complex with −5/−7 (sc: 4.78, c: 3.77) showing that cytogenetics remains it’s prognostic relevance independent from the therapy applied. In Kaplan-Meier-analyses median survival in pts. showing favourable karyotypes was 37.9 months with supportive treatment as compared to 26.4 months with chemotherapy (p<0.01). We observed no therapy-related survival differences with regard to patients of the unfavourable cytogenetic subgroup. The occurrence of complex abnormalities (n=670) was associated with an identical median survival comparing the therapy groups (c: 7.0, sc: 7.1 months). We also investigated groups with distinct abnormalities (5q-, −7/7q-, +8, 20q-) and found significant differences in survival between the therapy groups: Patients with 5q- and 20q- benefited from supportive care while −7/7q- was related with a better survival when chemotherapy was applied. Patients with trisomy 8 showed no differences in survival. Regarding these data, chemotherapy response, expressed by survival, is closely associated with cytogenetics. Complex abnormalities always show a dramatically reduced outcome, independent from the therapeutic strategy.

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T-cell Prolymphocytic Leukemia

Cancer Control ◽

10.1177/107327489800500102 ◽

1998 ◽

Vol 5 (1) ◽

pp. 19-24 ◽

Cited By ~ 23

Author(s):

Estella Matutes

Keyword(s):

Differential Diagnosis ◽

T Cell ◽

Skin Lesions ◽

Cell Phenotype ◽

Biological Entity ◽

Trisomy 8 ◽

Prolymphocytic Leukemia ◽

Humanized Monoclonal Antibody ◽

Laboratory Features ◽

Precise Diagnosis

Background: T-cell prolymphocytic leukemia (T-PLL) is a post-thymic T-cell malignancy with aggressive clinical course. Although T-PLL has been referred to under different designations, it is a distinct clinico-biological entity and should be distinguished from other T-cell disorders. Methods: The literature on T-PLL is reviewed. Experience on the clinical and laboratory features, differential diagnosis, and therapy on a large series of T-PLL patients is presented. Results: T-PLL affects adults and occurs more frequently in men. The principal disease characteristics are organomegaly, skin lesions, and a raised lymphocyte count. Immunological markers show a post-thymic T-cell phenotype (TdT– CD2+ CD5+ CD3±) with strong expression of CD7. A CD4+ CD8– phenotype is seen in two thirds of cases. CD4 and CD8 are coexpressed in 25%, and a CD4– CD8+ phenotype is rare. Cytogenetics show a recurrent abnormality inv(14)(q11;q32) that is always associated to other aberrations (particularly iso8q or trisomy 8). Differential diagnosis between T-PLL and other T-cell malignancies is based on a constellation of clinical and laboratory features. Generally, T-PLL patients are refractory to the therapy used in lymphoid disorders. Median survival is short but is improving with the use of 2'-deoxycoformycin and the humanized monoclonal antibody, anti-CDw52 (Campath-1H). Conclusions: T-PLL is a distinct T-cell disorder with characteristic clinical and laboratory features and a poor prognosis. A precise diagnosis of this disease is important in determining patient management and treatment.

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Photosensitive or Congenital Porphyria with Hemolytic Anemia

Blood ◽

10.1182/blood.v6.8.685.685 ◽

1951 ◽

Vol 6 (8) ◽

pp. 685-698 ◽

Cited By ~ 41

Author(s):

ROBERT A. ALDRICH ◽

VIOLET HAWKINSON ◽

MOISES GRINSTEIN ◽

CECIL JAMES WATSON

Keyword(s):

Hemolytic Anemia ◽

Fluorescence Spectra ◽

Marked Decrease ◽

Skin Lesions ◽

Type I ◽

Laboratory Findings ◽

Essential Change ◽

Special Studies ◽

First Time ◽

Coproporphyrin I

Abstract 1. The clinical features, laboratory findings and special studies of a case of photosensitive (congenital) porphyria in a 4 year old girl have been presented. This case was of particular interest in view of severe hemolytic anemia with hepatosplenomegaly. 2. Copro- and uroporphyrin I were isolated from the urine and feces. The ratio of these porphyrins in the urine varied from 1:10, to 1:30 respectively, while in the feces the ratio was reversed at about 70:1. Coproporphyrin III was isolated in much smaller amount than the type I isomer, from both urine and feces. Isomer analyses of the coproporphyrins in the excreta indicated that approximately 98 per cent was type I. 3. Prior to splenectomy copro- and uroporphyrin I were isolated in crystalline form for the first time from circulating human erythrocytes. Coproporphyrin III was also isolated in lesser amount. Uroporphyrin I was crystallized from the plasma, which also contained coproporphyrin I. Microfluorospectrometry of the bone marrow revealed large amounts of porphyrin in the developing red cells. The porphyrin fluorescence spectra indicated that at least three porphyrins were present. 4. Splenectomy was followed by disappearance of uro- and coproporphyrins from the erythrocytes, and a marked decrease in plasma, urine and feces without any essential change in the type of porphyrins excreted. The metabolic defect porphyria, was still present, but now latent in character. Reduction in porphyrin excretion was apparently related to elimination of hypersplenic hemolysis and compensatory increase of erythropoiesis. Anemia and dermal photosensitivity to sunlight disappeared simultaneously with the reduction in porphyrin excretion. 5. Efforts to reproduce the skin lesions by artificial light were unsuccessful.

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Prognostic implications of morphology and karyotype in primary myelodysplastic syndromes

Blood ◽

10.1182/blood.v67.6.1765.bloodjournal6761765 ◽

1986 ◽

Vol 67 (6) ◽

pp. 1765-1772 ◽

Cited By ~ 2

Author(s):

RH Jacobs ◽

MA Cornbleet ◽

JW Vardiman ◽

RA Larson ◽

MM Le Beau ◽

...

Keyword(s):

Median Survival ◽

Myelodysplastic Syndromes ◽

Chromosomal Abnormalities ◽

Bone Marrow Cells ◽

Normal Karyotype ◽

Refractory Anemia ◽

Survival Times ◽

Trisomy 8 ◽

Leukemic Transformation ◽

Abnormal Karyotype

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.

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