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Blood Dec 1991We 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...
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.
Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Chromosome Aberrations; Chromosomes, Human, Pair 14; Female; Humans; Immunophenotyping; Karyotyping; Leukemia, Prolymphocytic; Male; Middle Aged; Pentostatin; Prognosis; Remission Induction; T-Lymphocytes
PubMed: 1742486
DOI: No ID Found -
Journal of Investigative Medicine High... 2021B-cell prolymphocytic leukemia (B-PLL) is a rare leukemia characterized by rapidly increasing leukocytosis with splenomegaly and lymphadenopathy. Treatment strategies...
B-cell prolymphocytic leukemia (B-PLL) is a rare leukemia characterized by rapidly increasing leukocytosis with splenomegaly and lymphadenopathy. Treatment strategies are largely based on studies of chronic lymphocytic leukemia (CLL). Antibodies against the cell surface protein CD20 are considered to be first-line therapy. A 76-year-old male with known CLL presented 2 weeks after starting chemoimmunotherapy for newly refractory CLL after failing ibrutinib therapy. White blood cell count was elevated at 226.7 × 10/µL. Fluorescent in situ hybridization analysis of a bone marrow specimen showed new development of complex cytogenetics. Flow cytometry revealed B cells appearing slightly dimmer on CD45 and brighter on CD20 compared with typical B-CLL suggestive of less mature lymphocyte forms. The patient was diagnosed with B-PLL and started on obinutuzumab and venetoclax with rapid normalization of white blood cells. This case recapitulates the challenges in diagnosing and treating B-PLL. Ibrutinib resistance is a growing area of study with several proposed mechanisms of acquired resistance. The pathogenesis of B-PLL is not completely understood, although mutations in are presumed to play a role.
Topics: Aged; Humans; Immunotherapy; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Male
PubMed: 33533282
DOI: 10.1177/2324709621990767 -
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 -
Cases Journal Jan 2010Therapy related second malignancy of the hematological system is small but real risk after adjuvant chemotherapy for breast cancer. It includes acute myeloid leukemia...
INTRODUCTION
Therapy related second malignancy of the hematological system is small but real risk after adjuvant chemotherapy for breast cancer. It includes acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS); however T-cell prolymphocytic leukemia (T-PLL) has not been described earlier in relation to breast cancer and its therapy. T-PLL is a rare chronic T-cell lymphoproliferative disease with a mature post-thymic T-cell immunophenotype and aggressive clinical course.
CASE PRESENTATION
A 45 year old Indian female of Nordic origin presented 5 years back with a lump in the right breast and the axilla. She underwent modified radical mastectomy. Histophotomicrograph of the excised breast lesion showed a 2.1 cm duct carcinoma, positive for ER and PR with 1 out of 25 lymph nodes positive for metastasis. She received 6 cycles of chemotherapy with cyclophosphamide, epirubicin, and 5-fluorouracil. This was followed by tamoxifen 20 mg per day for five years. She was doing well on follow up until the completion of fifth year of her disease, when she presented with complaints of mild fever and weakness. Examination revealed generalized lymph node enlargement along with hepatomegaly. Hemogram showed mild anemia, normal platelet count and a leukocyte count of 1.2 x 10(11)/L. Peripheral blood examination revealed medium sized lymphoid cells, constituting almost 75% of total nucleated cell population. Immunophenotying, established a diagnosis of post thymic T-cell prolymphocytic leukemia. Contrast-enhanced computed tomography of the chest and abdomen was done which revealed an anterior mediastinal mass with destruction of sternum along with multiple small nodular shadows in bilateral lung fields suggestive of lung metastasis. Fine needle aspiration cytology of the mass showed atypical ductal cells with nuclear pleomorphism, which were positive for ER, PR and Her2neu protein. This confirmed a co-existent metastatic breast carcinoma. She was started on chemotherapy for T-PLL along with hormonal therapy with aromatase inhibitor. Unfortunately, both her malignancies progressed after an initial stable disease of two months.
CONCLUSION
Our case describes the potential of breast chemotherapy to cause grave second hematological malignancies of the T-cell lymphoid lineage, not described earlier. Such events highlight the importance to identify those patients of breast cancer in whom chemotherapy can safely be avoided.
PubMed: 20076807
DOI: 10.1186/1757-1626-3-4 -
Cancer Aug 2003Pilot studies showed that alemtuzumab is active in lymphoproliferative disorders. The authors conducted a Phase II trial to evaluate the efficacy and safety of... (Clinical Trial)
Clinical Trial
BACKGROUND
Pilot studies showed that alemtuzumab is active in lymphoproliferative disorders. The authors conducted a Phase II trial to evaluate the efficacy and safety of alemtuzumab in advanced or refractory chronic lymphoproliferative disorders.
METHODS
Seventy-eight patients were enrolled. The most common diagnoses were chronic lymphocytic leukemia (n = 42 patients) and T-cell prolymphocytic leukemia (n = 18 patients). Before entering the study, the patients had received multiple therapies (median, three therapies) and the median time from diagnosis was 7 years. Alemtuzumab was given intravenously at doses of 3 mg, 10 mg, and 30 mg on 3 consecutive days, after which 30 mg was administered 3 times a week. Patients were treated for 4-12 weeks depending on disease response. All patients received prophylactic trimethoprim/sulfamethoxazole and valacyclovir.
RESULTS
The overall response rate was 35%, the complete response (CR) rate was 13%, and the partial response (PR) rate was 22%. The median duration of response was 18 months for patients achieving a CR and 7 months for patients achieving a PR. The median duration of survival was 25 months for patients who had a response and 12 months for the entire population. Normalization of the lymphocyte count was observed in 84% of patients and resolution of bone marrow involvement was observed in 49% of patients. The most common infusion-related adverse events were fever, rigors, skin rash, nausea, and dyspnea. These were most common during the first week of therapy. Hematologic toxicity was comprised of long-lasting lymphocytopenia and transient neutropenia and thrombocytopenia. Thirty-six patients (46%) experienced at least one episode of fever or infection.
CONCLUSIONS
Alemtuzumab has a high response rate in patients with chronic lymphoproliferative disorders.
Topics: Adult; Aged; Aged, 80 and over; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Agents; Humans; Immunocompromised Host; Infections; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Lymphoma; Middle Aged; Survival Rate
PubMed: 12910522
DOI: 10.1002/cncr.11551 -
Journal of Investigative Medicine High... 2018We report the case of a patient with B-cell prolymphocytic leukemia who was successfully treated with the novel humanized monoclonal antibody obinutuzumab. This patient...
We report the case of a patient with B-cell prolymphocytic leukemia who was successfully treated with the novel humanized monoclonal antibody obinutuzumab. This patient was previously treated with the combination of rituximab and bendamustine and had recurrent infusion reactions. Her treatment with rituximab and bendamustine was discontinued when she developed disease progression after 3 cycles of therapy. She was then treated with obinutuzumab 1000 mg on day 1 of every cycle and chlorambucil 0.5 mg/kg on days 1 and 15 every 28 days to which she had greater tolerability. After 4 cycles of treatment, she had resolution of her clinical symptoms, massive splenomegaly, and normalization of her white blood cell count.
PubMed: 30038912
DOI: 10.1177/2324709618788674 -
Annals of Oncology : Official Journal... Oct 2002To assess the activity and toxicity of 2-chlorodeoxyadenosine (cladribine, CDA) given by subcutaneous bolus injections to patients with hairy cell leukemia (HCL). (Clinical Trial)
Clinical Trial
BACKGROUND
To assess the activity and toxicity of 2-chlorodeoxyadenosine (cladribine, CDA) given by subcutaneous bolus injections to patients with hairy cell leukemia (HCL).
PATIENTS AND METHODS
Sixty-two eligible patients with classic or prolymphocytic HCL (33 non-pretreated patients, 15 patients with relapse after previous treatment, and 14 patients with progressive disease during a treatment other than CDA) were treated with CDA 0.14 mg/kg/day by subcutaneous bolus injections for five consecutive days. Response status was repeatedly assessed according to the Consensus Resolution criteria.
RESULTS
Complete and partial remissions were seen in 47 (76%) and 13 (21%) patients, respectively, for a response rate of 97%. All responses were achieved with a single treatment course. Most responses occurred early (i.e. within 10 weeks) after start of CDA therapy, but response quality improved during weeks and even months after treatment completion. The median time to treatment failure for all patients was 38 months. Leukopenia was the main toxicity. Granulocyte nadir (median 0.2 x 10(9)/l) was strongly associated with the incidence of infections (P = 0.0013). Non-specific lymphopenia occurred early after CDA treatment, and normal lymphocytes recovered slowly over several months. No significant associations were found between infections and nadir count of lymphocytes or any lymphocyte subpopulation. No opportunistic infections were observed.
CONCLUSIONS
One course of CDA given by subcutaneous bolus injections is very effective in HCL. The subcutaneous administration is more convenient for patients and care providers, and has a similar toxicity profile to continuous intravenous infusion. The subcutaneous administration of CDA is a substantial improvement and should be offered to every patient with HCL requiring treatment with CDA.
Topics: Adult; Aged; Antineoplastic Agents; Cladribine; Disease Progression; Female; Humans; Injections, Subcutaneous; Leukemia, Hairy Cell; Leukopenia; Male; Middle Aged; Recurrence; Survival
PubMed: 12377655
DOI: 10.1093/annonc/mdf272 -
Cancer May 2004Patients with chronic lymphocytic leukemia (CLL) that transforms to Richter syndrome (RS) frequently show atypical lymphocytes in bone marrow; however, a diagnosis of RS...
BACKGROUND
Patients with chronic lymphocytic leukemia (CLL) that transforms to Richter syndrome (RS) frequently show atypical lymphocytes in bone marrow; however, a diagnosis of RS requires confirmation of the presence of sheets of large cells in bone marrow or lymph nodes.
METHODS
In this study, the authors evaluated the clinical significance of scattered large cells in bone marrow. They assessed the possibility of predicting transformation to RS in bone marrow smears by counting the percentages of prolymphocytes and large cells in 78 patients with CLL and 29 patients with lymph node biopsy-confirmed RS.
RESULTS
The percentage of large cells was found to be correlated with decreasing survival in a continuous fashion (P = 0.006). It is interesting to note that patients who had > 7% large cells in the bone marrow and elevated beta(2)-microglobulin (beta(2)-M) levels (> 5 mg/L) had a survival duration identical to that of patients with RS, and these factors together were a strong predictor of RS (P < 0.001).
CONCLUSIONS
Patients with CLL who had bone marrow that contained > 7% large cells and who had beta(2)-M levels > 5 mg/L had a disease that was similar to RS, and the combination of large cells and beta(2)-M can be used as a surrogate marker for RS.
Topics: Adult; Aged; Aged, 80 and over; Biopsy; Bone Marrow Cells; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymph Nodes; Lymphocytes; Male; Middle Aged; Survival Rate; Syndrome; beta 2-Microglobulin
PubMed: 15139060
DOI: 10.1002/cncr.20251 -
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 -
Blood Aug 1987Monoclonal antibodies (MoAbs) were developed against the cCLLa, a 69-kilodalton leukemia-associated antigen expressed on malignant cells of B-type chronic lymphatic...
Monoclonal antibodies (MoAbs) were developed against the cCLLa, a 69-kilodalton leukemia-associated antigen expressed on malignant cells of B-type chronic lymphatic leukemia (B-CLL) and its variants: prolymphocytic (PLL) and hairy cell leukemias (HCL). Two hybridomas yielded approximately 2 and approximately 7.5 mg/mL of IgG2a kappa and IgM kappa, respectively. Monoclonal surface immunoglobulin-bearing cells of all B-CLL patients studied (n = 30) reacted with the MoAbs (r greater than .99) regardless of stage or lymphocyte count. This suggests that the malignant clone in CLL can be identified and its size monitored by using our MoAbs. In contrast, normal B lymphocytes, a large panel of normal, reactive and neoplastic cells, and malignant cell lines failed to react with either MoAb as judged by indirect immunofluorescence and by flow cytometry. Only two patients (one with non-Hodgkin's lymphoma, the other with acute myeloblastic leukemia) exhibited a small cell subset reactive with the MoAbs. cCLLa specificity was suggested by selective target cell reactivity and competitive inhibition-absorption and confirmed by immunoprecipitation. MoAbs IgG2a kappa and IgM kappa appeared to share antigenic determinants and were moderate and avid complement binders inducing 100% and 40% target cell lysis, respectively. cCLLa density on malignant CLL and HCL cells was estimated by equilibrium binding studies using the IgG2a kappa MoAb at 1.7 and 9 X 10(6)/cell, respectively. The restricted expression of the cCLLa and the specificity and cytolytic activity of the anti-cCLLa MoAbs support these antibodies as probes for the classification of lymphoproliferative diseases and for the specific diagnosis and treatment of B-CLL and its variants.
Topics: Antibodies, Monoclonal; Antibody Specificity; Antigens, Neoplasm; Complement System Proteins; Epitopes; Humans; Leukemia, Lymphoid
PubMed: 2440501
DOI: No ID Found