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Urology Annals 2017An 82-year-old man presented with high-grade fever, left flank pain with dysuria. Urine culture revealed the growth of . Contrast-enhanced computed tomography features...
An 82-year-old man presented with high-grade fever, left flank pain with dysuria. Urine culture revealed the growth of . Contrast-enhanced computed tomography features were suggestive of xanthogranulomatous pyelonephritis (XPN) of the left kidney. Serial hemogram studies revealed markedly raised white cell count with the presence of blast cells. On further evaluation by peripheral blood smears and bone marrow biopsy studies, a background disease setting of acute prolymphocytic leukemia was diagnosed. This is a very rare case report of acute leukemia masquerading as a case of XPN, and the optimum treatment protocol is yet to be established in such a scenario.
PubMed: 28479773
DOI: 10.4103/0974-7796.204179 -
The Permanente Journal 2016B-cell prolymphocytic leukemia (B-PLL) is a rare, aggressive leukemia distinct from chronic lymphocytic leukemia, with median survival of only 3 years. B-PLL is... (Review)
Review
INTRODUCTION
B-cell prolymphocytic leukemia (B-PLL) is a rare, aggressive leukemia distinct from chronic lymphocytic leukemia, with median survival of only 3 years. B-PLL is resistant to most chemotherapy and newer targeted therapies such as alemtuzumab and thalidomide. Phenylethyl isothiocyanate (PEITC) is a natural compound from horseradish with evidence for therapeutic potential in multiple leukemia types.
CASE PRESENTATION
Here we present a case report of a 53-year-old man whose chronic lymphocytic leukemia transformed to end-stage B-PLL, disqualifying him for allogenic stem cell transplantation. He was treated with PEITC followed by salvage R-CHOP (Rituximab, Cyclophosphamide, Hydroxydaunorubicin [doxorubicin hydrochloride], Oncovin [vincristine sulfate], Prednisone or Prednisolone) chemotherapy, which led to normalized white blood cell count and disease stabilization that requalified him for allogenic peripheral stem-cell transplant therapy. We conducted a systematic review to analyze and interpret the potential contribution of PEITC to his unexpectedly favorable R-CHOP response. Following sequential 8 weeks of PEITC/pentostatin and 6 cycles of R-CHOP, the patient received allogenic peripheral blood stem cell transplant on an outpatient basis and remains well at the time of this publication, with no evidence of CD20+ small B-cells.
DISCUSSION
Given the limited data for R-CHOP in B-PLL, this patient's recovery suggests presensitization of B-PLL cells toward R-CHOP, potentially justifying further investigation.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Isothiocyanates; Leukemia, Prolymphocytic, B-Cell; Male; Middle Aged; Outcome Assessment, Health Care; Salvage Therapy
PubMed: 27168399
DOI: 10.7812/TPP/15-153 -
Journal of Basic and Clinical Pharmacy Mar 2016Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature-appearing lymphocytes in blood, bone marrow, lymph nodes, and spleen with a median...
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature-appearing lymphocytes in blood, bone marrow, lymph nodes, and spleen with a median lymphocyte count of 20-30 × 10(9)/L at the time of diagnosis. In half of the patients, the lymphocyte count doubles over a period of 1-year and cyclic rise up to 50 × 10(9)/L can occur in untreated patients while in others the count may remain stable for years. Based on the cytogenetic and molecular studies, it has been demonstrated that multiple clones may occur in CLL and clonal evolution is a frequent occurrence. The transformation of CLL to a high-grade non-Hodgkin's lymphoma such as diffuse large B cell lymphoma, Hodgkin lymphoma, and prolymphocytic leukemia is well documented. Whereas the transformation of CLL to acute leukemia occurs in <1% cases and this contrasts the almost invariable progression in patients with chronic myeloid leukemia. Here, we report a rare case of a 55-year-old lady, a diagnosed case of CLL transforming into B-cell acute lymphocytic leukemia over a very short interval of 1 week period.
PubMed: 27057127
DOI: 10.4103/0976-0105.177702 -
El Bisturi 2016Prolymphocytic leukemias (PLLs) are rare mature lymphoid disorders of B- and T-cell subtypes with distinct features and an aggressive clinical course. PLL represents...
Prolymphocytic leukemias (PLLs) are rare mature lymphoid disorders of B- and T-cell subtypes with distinct features and an aggressive clinical course. PLL represents only 2% of all mature lymphocytic leukemias in adults. T-PLL represents 20% of all PLLs cases. T-cell prolymphocytic leukemia (T-PLL) is more rare and more rapidly progressive and aggressive than B-PLL; it is generally resistant to conventional chemotherapy, and historically the median survival has been about 7 months. Clinicians will often only see a case of T-PLL once every 5 to 10 years, which makes recognition of the disorder difficult. The prognosis is poor and there is no curative therapy. We report a 77-year-old male patient with T-PLL presenting with WBC count of 1,115,000. We will discuss the clinical, morphologic, immunophenotypic and cytogenetic features of this rare entity. A distinctive hematologic aspect of T-PLL is a rapidly rising white blood cell count with a doubling time of weeks to months. The key morphologic feature in the diagnosis of T-PLL is a population of more than 55% prolymphocytes in the peripheral blood. The diagnosis can be made on peripheral blood by flow cytometry where a monoclonal lymphocyte population will show positivity for T-cell markers. T-PLL is characterized by complex chromosomal abnormalities, which suggests that chromosomal aberrations might occur progressively during the course of the disease, thus explaining the aggressive nature of this condition. The main challenge as a clinician treating T-PLL is to deliver long-term disease-free survival. The most important predictor of outcome is response to alemtuzumab therapy (Campath). Knowledge of the disrupted pathways and mechanisms underlying activation and proliferation in T-PLL has raised the possibility of developing future and promising treatment approach that targets these pathways and signals by the use of future molecule inhibitors. T-PLL is a rare disease and careful attention should be given to correctly diagnose this T-cell leukemia. Physicians should be aware of this unusual entity. With the advent of alemtuzumab, although much progress has been made in the treatment of this disease, autologous or allogeneic hematologic stem cell transplant (HSCT) still remains the only hope for cure.
PubMed: 29238632
DOI: No ID Found -
Leukemia & Lymphoma 2016Previous experiments demonstrated that survival and proliferation of chronic lymphocytic leukemia (CLL) cells depends upon complex cross-talk between CLL cells and...
Previous experiments demonstrated that survival and proliferation of chronic lymphocytic leukemia (CLL) cells depends upon complex cross-talk between CLL cells and accessory cells in the tissue microenvironment. To further dissect these interactions in situ, we analyzed lymph nodes from 43 different patients infiltrated by CLL cells for expression of the chemokine CCL3, Ki-67, macrophages, and T cell subsets by immunohistochemistry. CCL3 expression was detected in 24 of 43 cases (56%), particularly in prolymphocytes and paraimmunoblasts within the proliferation centers. Significantly higher numbers of CD3+ T cells and CD57+ cells were noticed in CCL3 positive cases. Furthermore, denser infiltration of CLL lymph node tissues by CD57+ cells correlated with higher proliferation rates of the CLL cells. In conclusion, we demonstrate an association of CCL3 expression by CLL cells with increased numbers of CD3+ T cells and CD57+ cells in the lymph node microenvironment, which may promote CLL cell survival and proliferation.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chemokine CCL3; Disease Progression; Female; Gene Expression; Humans; Immunohistochemistry; Immunophenotyping; Leukemia, Lymphocytic, Chronic, B-Cell; Lymph Nodes; Lymphocyte Count; Macrophages; Male; Middle Aged; T-Lymphocyte Subsets; Tumor Microenvironment
PubMed: 26458057
DOI: 10.3109/10428194.2015.1068308 -
Science Translational Medicine Jun 2015T cell prolymphocytic leukemia (T-PLL) is a rare, mature T cell neoplasm with distinct features and an aggressive clinical course. Early relapse and short overall... (Clinical Trial)
Clinical Trial
T cell prolymphocytic leukemia (T-PLL) is a rare, mature T cell neoplasm with distinct features and an aggressive clinical course. Early relapse and short overall survival are commonplace. Use of the monoclonal anti-CD52 antibody alemtuzumab has improved the rate of complete remission and duration of response to more than 50% and between 6 and 12 months, respectively. Despite this advance, without an allogeneic transplant, resistant relapse is inevitable. We report seven complete and one partial remission in eight patients receiving alemtuzumab and cladribine with or without a histone deacetylase inhibitor. These data show that administration of epigenetic agents can overcome alemtuzumab resistance. We also report epigenetically induced expression of the surface receptor protein CD30 in T-PLL. Subsequent treatment with the anti-CD30 antibody-drug conjugate brentuximab vedotin overcame organ-specific (skin) resistance to alemtuzumab. Our findings demonstrate activity of combination epigenetic and immunotherapy in the incurable illness T-PLL, particularly in the setting of previous alemtuzumab therapy.
Topics: Aged; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Brentuximab Vedotin; Cell Proliferation; Chromatin; Drug Resistance, Neoplasm; Epigenesis, Genetic; Female; Gene Expression Regulation, Leukemic; Humans; Immunoconjugates; Ki-1 Antigen; Leukemia, Prolymphocytic, T-Cell; Leukocyte Count; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic; RNA, Messenger; Real-Time Polymerase Chain Reaction; STAT5 Transcription Factor; Skin; Treatment Outcome
PubMed: 26109102
DOI: 10.1126/scitranslmed.aaa5079 -
Journal of Clinical and Experimental... 2015T-cell prolymphocytic leukemia, small cell variant (T-PLL-s), is a rare lymphoid neoplasm associated with a poor prognosis. We encountered a case of T-PLL-s with a...
T-cell prolymphocytic leukemia, small cell variant (T-PLL-s), is a rare lymphoid neoplasm associated with a poor prognosis. We encountered a case of T-PLL-s with a characteristic phenotype. A 67-year-old female was referred to our hospital because of lymphocytosis in August 2013. Hepatosplenomegaly, lymphadenopathy, and skin lesions were absent. Hematologic examination revealed a white blood cell count of 17.9 × 10(9)/L with 81.2% mature lymphocytes, which were small with a high nuclear/cytoplasmic ratio, lacking a nucleolus and cytoplasmic granules. Anemia and thrombocytopenia were not observed. Flow cytometric analysis showed that these lymphocytes were positive for CD2, cyCD3, CD4, CD5, CD7, CD21, and CD38 (partially), but negative for smCD3, smTCR-αβ and -γδ, cyTCR-β, CD1a, CD8, CD25, HLA-DR, and terminal deoxynucleotidyl transferase. Polymerase-chain reaction analysis of cells from both the peripheral blood and the bone marrow demonstrated monoclonal rearrangement of TCR-γ. A possible rearranged band of the TCR-β gene was observed by Southern blot analysis. The karyotype of the marrow cells was 46, XX. A diagnosis of T-PLL-s, possibly at the stage of cytoplasmic CD3 expression in the ontogenesis of T-cells, was made. The patient has been asymptomatic, and the white blood cell count has gradually increased during one-year observation, being 69.0 × 10(9)/L with 89.7% lymphocytes in August 2014.
Topics: Aged; Antigens, CD; Blood Cell Count; Cell Transformation, Neoplastic; Female; Humans; Immunophenotyping; Leukemia, Prolymphocytic, T-Cell; Neoplasm Staging; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocytes
PubMed: 26106002
DOI: 10.3960/jslrt.55.17 -
PloS One 2014The EBV carrying lines MEC1 and MEC2 were established earlier from explants of blood derived cells of a chronic lymphocytic leukemia (CLL) patient at different stages of...
The EBV carrying lines MEC1 and MEC2 were established earlier from explants of blood derived cells of a chronic lymphocytic leukemia (CLL) patient at different stages of progression to prolymphocytoid transformation (PLL). This pair of lines is unique in several respects. Their common clonal origin was proven by the rearrangement of the immunoglobulin genes. The cells were driven to proliferation in vitro by the same indigenous EBV strain. They are phenotypically different and represent subsequent subclones emerging in the CLL population. Furthermore they reflect the clinical progression of the disease. We emphasize that the support for the expression of the EBV encoded growth program is an important differentiation marker of the CLL cells of origin that was shared by the two subclones. It can be surmised that proliferation of EBV carrying cells in vitro, but not in vivo, reflects the efficient surveillance that functions even in the severe leukemic condition. The MEC1 line arose before the aggressive clinical stage from an EBV carrying cell within the subclone that was in the early prolymphocytic transformation stage while the MEC2 line originated one year later, from the subsequent subclone with overt PLL characteristics. At this time the disease was disseminated and the blood lymphocyte count was considerably elevated. The EBV induced proliferation of the MEC cells belonging to the subclones with markers of PLL agrees with earlier reports in which cells of PLL disease were infected in vitro and immortalized to LCL. They prove also that the expression of EBV encoded set of proteins can be determined at the event of infection. This pair of lines is particularly important as they provide in vitro cells that represent the subclonal evolution of the CLL disease. Furthermore, the phenotype of the MEC1 cells shares several characteristics of ex vivo CLL cells.
Topics: B-Lymphocytes; Biomarkers; Cell Line, Tumor; Cell Proliferation; Clonal Evolution; Clone Cells; Disease Progression; Epstein-Barr Virus Nuclear Antigens; Gene Expression; Herpesvirus 4, Human; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Lymphocyte Count; Time Factors; Viral Matrix Proteins; Viral Proteins
PubMed: 25162594
DOI: 10.1371/journal.pone.0106008 -
Experimental Hematology & Oncology 2014T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive subtype of chronic lymphocytic leukemia. Usually it presents in older people with a median age of...
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive subtype of chronic lymphocytic leukemia. Usually it presents in older people with a median age of 61 years. T-PLL is characterized by elevated white blood cell (WBC) count with anemia and thrombocytopenia, hepatosplenomegaly, and lymphadenopathy; less common findings are skin infiltration and pleural effusions. The most frequent chromosomal abnormalities in T-PLL include 14q11.2, chromosome 8, and 11q rearrangements. Also deletions in the short arm of a chromosome 9 are reported in ~30% of T-PLL together with other aberrations. Here we report a childhood T-PLL case with a de novo del(9)(p13) as sole acquired anomaly leading to monosomy of the tumor suppressor gene CDKN2A (cyclin-dependent kinase inhibitor 2A). Also, to the best of our knowledge this is the first case of a childhood T-PLL with this aberration.
PubMed: 25954594
DOI: 10.1186/2162-3619-3-28