SummarySome cases of T-cell acute lymphoblastic leukaemia (ALL) express markers found in natural-killer (NK) cells, such as CD56 and CD16. Out of 84 T-cell ALL cases diagnosed at our Institution, CD56 and/or CD16 was detected in 24 (28AE5%), which we designated T/NK-ALL group. Clinical features, laboratory characteristics, survival and expression of cytotoxic molecules were compared in T/NK-ALL and T-ALL patients. Significant differences were observed regarding age (24AE9 vs. 16AE4 years in T/NK-ALL and T-ALL, respectively, P = 0AE006) and platelet counts (177 · 10 9 /l vs. 75 · 10 9 /l in T/NK-ALL and T-ALL, respectively, P = 0AE03). Immunophenotypic analysis demonstrated that CD34, CD45RA and CD33 were more expressed in T/NK-ALL patients, whereas CD8 and terminal deoxynucleotidyl transferase were more expressed in T-ALL patients (P < 0AE05). The mean overall survival (863 vs. 1869 d, P = 0AE02) and disease-free survival (855 vs. 2095 d, P = 0AE002) were shorter in patients expressing CD56/CD16. However, multivariate analysis identified CD56/CD16 as an independent prognostic factor only for DFS. Cytotoxic molecules were highly expressed in T/NK-ALL compared to T-ALL. Perforin, granzyme B and TIA-1 were detected in 12/17, 4/17 and 7/ 24 T/NK-ALL patients and in 1/20, 0/20 and 1/20 T-ALL respectively (P < 0AE001, P = 0AE036 and P = 0AE054). Therefore, the presence of CD56/ CD16 was associated with distinct clinical features and expression of cytotoxic molecules in the blasts.

We report a case of T-cell prolymphocytic leukemia (T-PLL) in a 41-year-old male. Classical cytogenetic, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) studies of a blood sample obtained at diagnosis revealed the co-existence of t(X;14)(q28;q11), t(Y;14)(q12;q11) and a ring chromosome derived from i(8)(q10). Immunophenotypic studies revealed involvement of T-cell lineage, with proliferation of CD4(-) CD8+. The co-existence of two translocations involving both sex chromosomes in a case of T-PLL is rare. Chromosomal instability associated with the disease progression may have allowed the emergence of cell clones with translocations involving the sex chromosomes and the ring chromosome observed.

We report the findings of the immunophenotypic profile of three cases of nasal T/NK cell lymphoma in leukemic phase. Flow cytometry analysis was carried out using cell suspensions of tumor nasal biopsies and peripheral blood. Tumor samples were composed by a mixture of a predominant subset of medium-size true NK cytCD3epsilon-, sCD3epsilon-, CD56+ cells mixed with a minor subset of medium-size T/NK sCD3epsilon+, CD56+ cells. Both subsets were also detected in peripheral blood. In addition, an infiltration of small-size sCD3epsilon+, CD56- normal T lymphocytes was also present.

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Objective: To report the outcomes of a systematic literature review of guidelines and consensus on the management of paroxysmal nocturnal hemoglobinuria (PNH) and describe the main therapeutic options available worldwide. Methods: A systematic literature review was conducted in April 2018 with no time limit and reported in line with the PRISMA statement. The AGREE II instrument was used to determine the quality of each guideline included in the systematic review. Results: Eight guidelines/consensus were eligible, one developed by an international group, two in Spain, and one each in Turkey, Germany, Argentina, Australia and the United Kingdom. Supportive treatment with erythrocyte transfusion, anticoagulants and steroids is indicated by all guidelines and consensus. The use of erythropoietin is suggested by three of them. Recommendations for the prescription of eculizumab were consistent in all but one guideline, published in 2005. Allogeneic hematopoietic stem cell transplantation is reported as the only potentially curative treatment for PNH, although its association with high mortality and morbidity rates is emphasized, being indicated for a selected group of patients. The AGREE II scores applied for each domain showed in general a low and heterogeneous methodological quality among guidelines. Conclusion: Despite the low and heterogeneous methodological quality, in general the comparison of guidelines and consensus for PNH management showed consistent recommendations regarding supportive care, eculizumab and hematopoietic stem cell transplantation.

Rearrangements of the long arm of chromosome 11 are commonly associated with acute leukemias, with the breakpoints clustered mainly to the 11q23 region, frequently leading to the rearrangement of the MLL gene. CCND1 (previously PRAD1, BCL1), the gene encoding cyclin D1, is located at 11q13. Overexpression of cyclin D1 represents one of the common genetic alterations in human neoplasia, leading to a change in G1-S transition and uncontrolled cell growth. Here we describe the case of a patient with acute myelogenous leukemia (AML) harboring a chromosomal translocation involving 11q13 and a new partner, chromosome 5. A 30-year-old male presented with dyspnea for one month and peripheral blood counts of: hemoglobin 4.9 g/dL, platelets 62 x 109/L and leukocytes 29.5 x 109/L (with 45% of blasts). Bone marrow examination showed a hypercellular marrow with 82% blasts positive for myeloperoxidase and negative for non-specific esterase. The case was classified as AML M2 according to FAB. Classical cytogenetics and spectral karyotyping (SKY) studies performed by unsynchronized culture of the marrow cells revealed an abnormal clone of 46,XY, t(5;11)(q35;q13)[20]. RT-PCR for the rearrangements MLL/AF9, MLL/AF6, MLL/AF4, MLL/ENL, and MLL/ELL were performed and were negative for all of them. Cyclin D1 overexpression was not detected in bone marrow cells by Real Time PCR. The patient was submitted to induction chemotherapy with Daunorrubicin and Cytarabine but obtained only partial remission after 2 cycles of chemotherapy (10% of blasts in bone marrow after second induction). He was than submitted to an allogeneic stem cell transplantation (SCT) from his HLA identical sister. On day +30 after SCT he was in complete hematological remission. The classical cytogenetics study after chemotherapy and bone marrow transplantation revealed karyotypes 46,XY[20] and 46,XX[15]/46,XY[15]chi, respectively. The t(5;11)(q35;q13) represents a recurrent abnormality in renal oncocytoma (benign tumors that occur predominantly in the kidney) and leads frequently to cyclin D1 overexpression. Nevertheless, this cromossomal translocation has never been described in AML.

T-cell prolymphocytic leukemia (T-PLL) is a malignant proliferation of lymphoid cells with a mature postthymic phenotype. The disease is characterized by lymphadenopathy, splenomegaly, skin lesions, and elevated white blood cell count, and it is often resistant to conventional therapy. Classic cytogenetic studies have revealed the presence of complex karyotypes and some recurrent chromosomal abnormalities, of which the most frequent are t(14;14)(q11;q32), inv(14)(q11q32), t(X;14)(q28;q11), i(8)(q10), and t(8;8)(p12;q11). Conventional cytogenetic techniques are insufficient to fully characterize chromosomal abnormalities, especially complex and cryptic aberrations. In this report, we describe a case of T-PLL with t(Y;14)(q12;q11) and a ring chromosome r[i(8)(q10)] studied by classic cytogenetics and spectral karyotyping (SKY). These abnormalities have not been previously described in T-PLL. A 41-year-old man was admitted with night sweats, weight loss, lymphadenopathy and hepatosplenomegaly without skin rash. Peripheral blood counts were: platelets 128 x 109/L and leukocytes 93.6 x 109/L. Hemoglobin levels were 12.5 g/dL. Immunophenotypic studies showed the following results: CD2+, CD3+, CD5+, CD7+, CD4−, CD8+, T-cell receptor (TCR) a/b+, CD1-, and terminal deoxynucleotidyl transferase-negative (TdT-). The patient was treated with fludarabine and CHOP therapy, neither of which resulted in a response. The patient was then treated with alemtuzumab (Campath®) and complete resolution of lymphadenopathy and normalization of blood counts was achieved. Classic cytogenetic and SKY analyses were performed on a 3-day phytohemagglutinin-stimulated culture of peripheral blood lymphocytes. The observed karyotype was abnormal in 18 of the metaphases analyzed: 46, t(X;14)(q28;q11), t(Y;14)(q12;q11), r[i(8)(q10)]. The co-existence of 2 translocations involving both sex chromosomes in P-TLL is a rare occurrence; however, abnormalities involving band Xq28 (the site for the MCTP-1B1 gene which has homology to TCL-1 on 14q32.1) are common in T-PLL. In addition, translocations involving the 14q11-q13 region (TCRa and TCRd) result in juxtaposition of enhancer elements responsible for the expression of TCR genes next to different oncogene loci. This leads to disruption of transcriptional pathways involved in normal T cell development, and ultimately, leukemic transformation. The fibroblast growth factor receptor-1 (FGFR-1) gene, in 8p11, has been implicated in a recurrent breakpoint in a myeloproliferative syndrome associated with T-cell lymphoma and the monocytic leukemia zinc finger (MOZ) gene in acute myelogenous leukemia. The amplification of the q arm of chromosome 8 accompanied by deletion of 8p sequences distal to the breakpoints could mean that two events act synergistically to contribute to the malignant phenotype in T-PLL. It is possible to suggest that the loss of a tumor suppressor gene or activation of an oncogene on 8p cooperates with amplification of the q arm and/or the expression of TCL-1/MTCP-1B1 in T-PLL. Secondary abnormalities of chromosome 8 may play an important role in the development of T-PLL. In this case of T-PLL with rare cytogenetic abnormalities, treatment with alemtuzumab resulted in a clinical response.

T-prolymphocytic leukemia (T-PLL) is an aggressive T-cell leukemia characterized by the proliferation of prolymphocytes with a mature postthymic T-cell phenotype and commonly involves the blood, bone marrow, lymph nodes, liver, spleen, and skin. Leukemic cells appear as small to medium-sized prolymphocytes or small variant cells, occasionally with cerebriform nuclei. T prolymphocytes are CD2+, CD3+, and CD7+ and may express CD4+CD8−, CD4+CD8+, or CD4−CD8+ markers. The most frequent chromosomal abnormalities are t(14;14)(q11;q32), inv(14)(q11q32), t(X;14)(q28;q11), i(8)(q10), and t(8;8)(p12;q11). Although patients treated with conventional chemotherapy generally have a poor prognosis, alemtuzumab (Campath®) has been associated with good clinical responses in patients with T-PLL. Routine cytogenetic analysis to determine the response to alemtuzumab has not been performed in patients with T-PLL. This study reports the complete cytogenetic remission achieved following alemtuzumab treatment in a single patient with T-PLL. The 41-year old male patient presented with weight loss, night sweats, diffuse lymphadenopathy and hepatosplenomegaly, in the absence of any skin rash. Peripheral blood counts were: platelets 128 x 109/L and leukocytes 93.6 x 109/L, and hemoglobin values were 12.5 g/dL. The lymphocytes were mostly medium-sized with round to irregular nuclei; some cerebriform cells were also observed, with intermediate chromatin, single evident nucleoli, and a basophilic cytoplasm. Human T-cell lymphotrophic virus-1 serology was negative. Immunophenotypic studies showed CD2+, CD3+, CD5+, CD7+, CD4−, CD8+, CD1−, terminal deoxynucleotidyl transferase-negative (TdT-), and T-cell receptor a/b+. Classic cytogenetics and spectral karyotyping (SKY) were performed and an abnormal karyotype was observed in 18 metaphases analyzed: 46, t(X;14)(q28;q11), t(Y;14)(q12;q11), r[i(8)(q10)]. These abnormalities have not been previously reported in cases of T-PLL. The patient then underwent chemotherapy with CHOP, and subsequent therapy with fludarabine. The patient was then treated with alemtuzumab, 30 mg twice a week, for a total of 7 doses. The patient achieved complete clinical, hematological, and cytogenetic remission, characterized by lack of symptoms, reduction of lymph nodes, liver, and spleen size to normal volumes, and the disappearance of prolymphocytes from peripheral blood. Cytogenetic studies performed 7 months after treatment by classic cytogenetics and SKY revealed a karyotype of 46,XY[20]. This study is the first to demonstrate a complete cytogenetic remission following treatment with alemtuzumab in a patient with T-PLL that was refractory to standard chemotherapy. This is especially impressive in a patient with a complex karyotype and with different cytogenetic alterations not previously described.