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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 Clinical Pathology May 1994A case of a 58 year old woman with a chronic lymphoproliferative disorder of unusual clinical presentation, disease course, and immunophenotype is presented. At...
A case of a 58 year old woman with a chronic lymphoproliferative disorder of unusual clinical presentation, disease course, and immunophenotype is presented. At diagnosis she had severe anaemia, moderate lymphocytosis with some cells having prolymphocytoid features and a normal platelet count. A clinical examination yielded negative results. Only anaemia related symptoms were found and the patient became blood transfusion dependent. Both the lymphocytosis and the proportion of prolymphocytoid cells rose insidiously and thrombocytopenia developed later during the course of the disease. Three years later, the patient had a white cell count of 269 x 10(9)/l almost exclusively of prolymphocytoid cells and the bone marrow was diffusely infiltrated. She was refractory to chemotherapy and the anaemia did not improve after treatment with cyclosporine. Lymphoid cells were positive for cytoplasmatic CD3, HLA-Dr, CD34, CD38, CD7, CD56, CD13, CD33 and CD65. Membrane alpha beta and gamma delta T cell receptors (TCRs) were not expressed and the beta chain TCR gene was in germline configuration. Other membrane T, B, natural killer, and myelomonocytic markers were negative. Karyotype analysis was tried several times but metaphases were not obtained, even after stimulation with T cell mitogens.
Topics: Anemia; Antigens, CD; Antigens, Neoplasm; Chronic Disease; Female; Humans; Immunophenotyping; Leukemia, Prolymphocytic; Middle Aged
PubMed: 8027401
DOI: 10.1136/jcp.47.5.461 -
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 -
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 -
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 -
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 -
The American Journal of Case Reports May 2020BACKGROUND Most patients with chronic lymphocytic leukemia (CLL) are asymptomatic at diagnosis, but 10% present with B symptoms. Most patients have palpable...
Subcutaneous Masses as an Unusual Manifestation of Relapse in a Case of Atypical Chronic Lymphocytic Leukemia with Prolymphocytoid Transformation and Complex Karyotype: A Diagnostic Dilemma and Treatment Challenge.
BACKGROUND Most patients with chronic lymphocytic leukemia (CLL) are asymptomatic at diagnosis, but 10% present with B symptoms. Most patients have palpable lymphadenopathy, while 20-50% of the patients have hepatosplenomegaly. Cutaneous infiltrations in patients with CLL can be localized or generalized in the form of erythematous papules, plaques, nodules and, ulceration, which is uncommon. CASE REPORT We present the case of a 71-year-old man diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with atypical immunophenotype and increased prolymphocytes (CLL/PLL), which was treated initially after white blood counts (WBC) doubling with Bendamustine and Rituximab for 6 cycles, and achieved complete remission. The patient relapsed after 6 months of completion of treatment, with multiple large subcutaneous masses, proved to be infiltration with the same atypical CLL/SLL on tissue biopsy, with pathologic features indicating disease progression. The lack of similar reported cases, and the aggressiveness of the tumor clinically and histopathologically, resulted in the decision to treat with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone (R-CHOP) as a case of aggressive lymphoma, with complete remission clinically and radiologically. CONCLUSIONS We present a rare case of subcutaneous extramedullary masses of atypical CLL/SLL. The high proliferation index (Ki-67) and the increase of large cells are suggestive of aggressive progression of the disease; however, no frank features of Richter's transformation were noted. Based on this and because of the unusual aggressive-looking skin masses, the panel decided to treat the patient with R-CHOP. The impact of this presentation on the prognosis of the disease is not clear. To date, our patient has responded well to treatment with R-CHOP, with complete remission of the subcutaneous masses and on PET scan, but further follow-up is needed.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease Progression; Doxorubicin; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemic Infiltration; Male; Prednisone; Remission Induction; Rituximab; Subcutaneous Tissue; Vincristine
PubMed: 32388531
DOI: 10.12659/AJCR.920411 -
Blood Jan 2008The T-cell leukemia 1 (TCL1) oncoprotein is overexpressed by chromosomal rearrangement in the majority of cases of T-cell prolymphocytic leukemia (T-PLL). In vitro, TCL1...
The T-cell leukemia 1 (TCL1) oncoprotein is overexpressed by chromosomal rearrangement in the majority of cases of T-cell prolymphocytic leukemia (T-PLL). In vitro, TCL1 can modulate the activity of the serine-threonine kinase AKT, a downstream effector of T-cell receptor (TCR) signaling. In a series of 86 T-PLL tumors, we show that expression of TCR, and levels of TCL1 and activated AKT are adverse prognostic markers. High-level TCL1 in TCR-expressing T-PLL is associated with higher presenting white blood cell counts, faster tumor cell doubling, and enhanced in vitro growth response to TCR engagement. In primary tumors and TCL1-transfected T-cell lines, TCR engagement leads to rapid recruitment of TCL1 and AKT to transient membrane activation complexes that include TCR-associated tyrosine kinases, including LCK. Pharmacologic inhibition of AKT activation alters the localization, stability, and levels of these transient TCL1-AKT complexes and reduces tumor cell growth. Experimental introduction and knockdown of TCL1 influence the kinetics and strength of TCR-mediated AKT activation. We propose that in T-PLL, TCL1 represents a highly regulated, targetable modulator of TCR-mediated AKT growth signaling.
Topics: Cell Division; Gene Expression Regulation, Leukemic; Humans; Immunophenotyping; Leukemia, Prolymphocytic; Leukemia, T-Cell; Phosphorylation; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptors, Antigen, T-Cell; Signal Transduction; T-Lymphocytes
PubMed: 17890451
DOI: 10.1182/blood-2007-07-101519 -
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