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Oncology AND Lymphadenopathy, generalized [keywords]
- Allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia (ALL) in first complete remission. [Journal Article, Meta-Analysis, Review]
- Cochrane Database Syst Rev 2011; (10):CD008818.
Consolidation chemotherapy, autologous hematopoietic cell transplantation (HCT) and allogeneic HCT represent potential treatment alternatives for post-remission therapy in adult acute lymphoblastic leukemia (ALL), but there is genuine uncertainty regarding the optimal approach.To assess the effect of matched sibling donor vs. no donor status for adults with ALL in first complete remission (CR1).We performed a search of CENTRAL, MEDLINE and EMBASE electronic databases in September 2010 along with handsearching of literature cited in relevant primary articles, search of abstracts from American Society of Hematology and American Society of Clinical Oncology meetings, as well as consultation with content experts in the field.Review was performed by two authors, and Inclusion criteria included the following: controlled trials with donor vs. no donor comparison with assignment by genetic randomizationin adults with ALL in CR1.We extracted data on benefits (overall survival, progression-free survival) and harms (treatment-related mortality, relapse) of compared treatments. Adverse events were considered, but analysis of individual adverse events was not possible from the reported literature. We pooled summary results from each study using a random-effects model. We assessed heterogeneity. We performed subgroup analyses for disease risk categories. We performed sensitivity analyses according to methodological quality.A total of 14 relevant trials were identified, consisting of a total of 3157 patients. There was a statistically significant overall survival advantage in favor of the donor versus no donor group (HR 0.86; 95% CI 0.77 to 0.97; P = 0.01), as well as significant improvement in disease-free survival in the donor group(HR 0.82; 95% CI 0.72 to 0.94; P = 0.004). Those in the donor group had significant reduction in primary disease relapse(RR 0.53; 95% CI 0.37 to 0.76; P = 0.0004) and significant increase in non-relapse mortality(RR 2.8; 95% CI 1.66 to 4.73; P = 0.001). Significant heterogeneity was detected in analysis of relapse (Chi(2) 40.51, df = 6, P < 0.00001; I(2) = 85%). In regard to methodologic quality, the majority of included studies were free of selective reporting, and performed analyses according to intention to treat. Conversely, few reported sample size calculation that informed the study design. While blinding was considered as an important domain of methodological quality, none of the studies reported on whether any of the study personnel were blinded (e.g. subjects, personnel, outcome assessors, data analysts etc). Therefore, we did not consider blinding further in the analysis of methodological quality in this review.The results of this systematic review and meta-analysis support matched sibling donor allogeneic hematopoietic cell transplantation as the optimal post-remission therapy in ALL patients aged 15 years or over. This therapy offers superior overall survival and disease-free survival, and significantly reduces the risk of disease relapse, but does impose an increased risk of non-relapse mortality. Importantly these data are based on adult ALL treated with largely total body irradiation-based myeloablative conditioning and sibling donor transplantation and, therefore, cannot be generalized to pediatric ALL, alternative donors including HLA (human leukocyte antigen) mismatched or unrelated donors, or reduced toxicity or non-myeloablative conditioning regimens.
- Survival and death signals can predict tumor response to therapy after oncogene inactivation. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- Sci Transl Med 2011 Oct 5; 3(103):103ra99.
Cancers can exhibit marked tumor regression after oncogene inhibition through a phenomenon called "oncogene addiction." The ability to predict when a tumor will exhibit oncogene addiction would be useful in the development of targeted therapeutics. Oncogene addiction is likely the consequence of many cellular programs. However, we reasoned that many of these inputs may converge on aggregate survival and death signals. To test this, we examined conditional transgenic models of K-ras(G12D)--or MYC-induced lung tumors and lymphoma combined with quantitative imaging and an in situ analysis of biomarkers of proliferation and apoptotic signaling. We then used computational modeling based on ordinary differential equations (ODEs) to show that oncogene addiction could be modeled as differential changes in survival and death intracellular signals. Our mathematical model could be generalized to different imaging methods (computed tomography and bioluminescence imaging), different oncogenes (K-ras(G12D) and MYC), and several tumor types (lung and lymphoma). Our ODE model could predict the differential dynamics of several putative prosurvival and prodeath signaling factors [phosphorylated extracellular signal-regulated kinase 1 and 2, Akt1, Stat3/5 (signal transducer and activator of transcription 3/5), and p38] that contribute to the aggregate survival and death signals after oncogene inactivation. Furthermore, we could predict the influence of specific genetic lesions (p53⁻/⁻, Stat3-d358L, and myr-Akt1) on tumor regression after oncogene inactivation. Then, using machine learning based on support vector machine, we applied quantitative imaging methods to human patients to predict both their EGFR genotype and their progression-free survival after treatment with the targeted therapeutic erlotinib. Hence, the consequences of oncogene inactivation can be accurately modeled on the basis of a relatively small number of parameters that may predict when targeted therapeutics will elicit oncogene addiction after oncogene inactivation and hence tumor regression.
- Peripheral T-cell lymphoma with a regulatory T-cell phenotype: report of a nodal and an extranodal case from Peru. [Case Reports, Journal Article]
- Appl Immunohistochem Mol Morphol 2012 Mar; 20(2):196-200.
T-cell regulatory lymphocytes (T reg) are identified by their reactivity with CD4, CD25, and FOXP3, and are variably present in the background of various neoplasms including hematopoietic tumors, and function modulating the immune response, including control of autoimmunity. Adult T-cell leukemia/lymphoma is an aggressive lymphoma associated with human T-lymphotrophic virus 1 infection characterized by the presence of neoplastic lymphocytes with a T reg phenotype; however, this phenotype is not characteristically found in other lymphomas. Here, we report 2 apparently immunocompetent human T-lymphotrophic virus 1-negative patients with nodal and extranodal peripheral T-cell lymphoma, not otherwise specified with a T reg immunophenotype, based on the strong CD25 and FOXP3 positivity of the neoplastic cells. One patient was a 48-year-old woman with an early stage tumor in the cavum, who despite of chemotherapy subsequently developed systemic disease and died of tumor progression 46 months from diagnosis. The second patient was a 65-year-old male with generalized adenopathy and B symptoms who received chemotherapy achieving a complete remission but had recurrence and died 36 months from diagnosis. The histopathology revealed a diffuse infiltrate with an interfollicular distribution in the second case, with nodal involvement, consisted of large cells with clear cytoplasm associated with vascular proliferation and abundant mitoses. Neoplastic cells of first case showed typical T reg phenotype, whereas the second case had a CD4/CD8 double negative T reg variant. Only a single similar case was found in a review of the literature. We conclude that peripheral T-cell lymphoma, not otherwise specified with a T reg phenotype may represent a distinct category of T-cell lymphoma with an aggressive clinical course and poor prognosis.
- Survival outcome of childhood acute lymphoblastic leukemia in India: a resource-limited perspective of more than 40 years. [Journal Article]
- J Pediatr Hematol Oncol 2011 Aug; 33(6):475-9.
The outcome of childhood acute lymphoblastic leukemia in India has been inferior to more than 80% cure rates in developed nations. This study was done to analyze the outcome of acute lymphoblastic leukemia in India over 4 decades. There has been a gradual improvement in survival rates of up to >70% in some centers along with a decline in relapse and mortality. However, these results cannot be generalized to the entire nation. There is a crying need to address treatment abandonment, take quality improvement, educational and financial initiatives; cooperative research into risk factors and disease biology, and the implementation of risk stratification along with the assessment of response to therapy.
- Treatment strategies in limited stage follicular NHL. [Journal Article, Review]
- Best Pract Res Clin Haematol 2011 Jun; 24(2):179-86.
Limited stage (I-II) follicular lymphoma is an uncommon entity, since most patients with this disease have generalized adenopathy (stage III) or bone marrow involvement (stage IV). Although patients who present with stage III-IV disease often are considered to be incurable, ~50% of patients with limited disease will enjoy long-term freedom-from progression, usually following treatment with radiation therapy. Relapse among these patients is uncommon after 10 years and exceedingly rare after 15 years. Radiation treatment is generally restricted to the involved nodal region(s) with modest (~5 cm.) extension proximally and distally. Radiation dose is generally 30 Gy, but may be boosted slightly (36 Gy total) in the presence of bulky disease. Randomized clinical trials have been insufficiently powered to define the value of any additional treatment beyond radiation therapy, although single arm studies suggest a benefit to the addition of chemotherapy. There have been no reported experiences with chemo-immunotherapy or radioimmunotherapy. Patients should be monitored during follow up to identify transformation to a more aggressive lymphoma.
- Positive HIV ELISA test, autoimmune hemolytic anemia, and generalized lymphadenopathy: a unifying diagnosis. [Case Reports, Journal Article]
- Am J Hematol 2011 Aug; 86(8):690-3.
- Synchronous intravascular large B-cell lymphoma within meningioma. [Case Reports, Journal Article]
- Neuropathology 2012 Feb; 32(1):77-81.
Intravascular large B-cell lymphoma is a rare and aggressive lymphoma with a dismal prognosis. Synchronous intravascular large B-cell lymphoma within meningioma has not previously been documented. We report a case of a 73-year-old woman of Asian descent who presented with fever of unknown origin with generalized weakness. CT scan and MRI of the head revealed a dural-based mass lesion consistent with meningioma in the left frontal cerebral convexity. Surgery was performed to remove the tumor and histopathology showed a meningioma within which was a synchronous intravascular large B-cell lymphoma. The hematology and oncology services were consulted and palliative treatment was initiated due to the patient's poor Eastern Cooperative Oncology Group performance status. The patient died within 30 days post-surgery. To the best of our knowledge, this case represents the first report of synchronous intravascular large B-cell lymphoma within a meningioma.
- Acute lymphoblastic leukaemia presenting with severe hypercalcaemia. [Case Reports, Journal Article]
- Mymensingh Med J 2011 Jan; 20(1):134-7.
Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Usually ALL children present with pallor, fever, bleeding, infection, lymphadenopathy and hapatosplenomegaly. Very rarely ALL patients may present with hypercalcaemia and osteolytic lesions. A five year old boy was referred and transferred to the paediatric ward of Bangabandhu Sheikh Mujib Medical University, Dhaka with the complaints of pain in the hip joint, generalized pain all over the body and very high calcium level. He was severely pale, the total leukocyte count was normal with normal distribution. Platelet count was also normal. There were some atypical lymphocytes. Radiology showed extensive osteolytic lesions. Considering all these findings, a bone marrow study was done, which was compatible with ALL. Flow-cytometry was also done and it confirmed the diagnosis as common ALL.
- Generalized lymphadenopathy: unusual presentation of prostate adenocarcinoma. [Journal Article]
- Case Rep Urol 2011.:439732.
Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. Here, we report the case of a 59-year-old male patient with supraclavicular, mediastinal, hilar, and retroperitoneal and inguinal lymphadenopathy, which suggested the diagnosis of lymphoma. There were no urinary symptoms. A biopsy of the inguinal lymph node was compatible with adenocarcinoma, whose prostatic origin was shown by immunohistochemical staining with PSA. The origin of the primary tumor was confirmed by directed prostate biopsy. We emphasize that a suspicion of prostate cancer in men with adenocarcinoma of undetermined origin is important for an adequate diagnostic and therapeutic approach.
- Pediatric anaplastic large cell lymphoma presenting as generalized lymphadenopathy. [Case Reports, Journal Article]
- Oncology (Williston Park) 2010 Sep; 24(10):954-6, 958.
Because a finding of generalized lymphadenopathy can be associated with such a wide range of diseases and conditions, determining its cause can sometimes be challenging. Infectious causes are the most common; however, it is important also to consider other entities in the workup. Here we present the case of a 3-year-old girl with generalized lymphadenopathy and fever, in whom the cause of the symptoms was initially thought to be infectious. Ultimately, however, anaplastic large cell lymphoma (ALCL) was diagnosed. Using this case as a backdrop, we discuss the wide range of systemic illnesses that the differential diagnosis of generalized lymphadenopathy encompasses--including infectious, autoimmune, and oncological disorders. We discuss the different findings typically seen in the various entities that figure prominently in the differential, and we outline investigations that can help narrow it. Finally, we present an overview of ALCL, one of the more rare pediatric malignancies.