Ravi Krishnadasan

Interests

No activities entered.

Courses

Scholarly Contributions

Chapters

• Kumar, A., Krishnadasan, R., & Sundararajan, S. (2016). T-cell Prolymphocytic Lymphoma. In Handbook of Hematologic Malignancies 1st Edition.

Journals/Publications

• Peshin, S., Rahimuddin, B., Dharia, A., Singh, S., Kapadia, C., & Krishnadasan, R. (2025). Caught in the Crossfire: A Case of Splenic Infarction Amid G-CSF therapy in Chronic Myelomonocytic Leukaemia. European journal of case reports in internal medicine, 12(3), 005007.
  More info

  This report highlights a rare but significant complication associated with the use of granulocyte-colony stimulating factor (G-CSF) therapy, specifically splenic infarction, in a 67-year-old male with chronic myelomonocytic leukaemia (CMML) undergoing chemotherapy. G-CSFs, such as pegfilgrastim, are frequently used to prevent febrile neutropenia in cancer patients undergoing myelotoxic chemotherapy. While G-CSF is effective in reducing the risk of neutropenia, its administration has been linked to uncommon but severe complications such as splenic infarction and rupture. Our patient, receiving dose-dense chemotherapy with G-CSF support, developed severe abdominal pain midway through treatment. A computed tomography (CT) scan revealed multiple splenic hypodensities consistent with splenic infarction, but no active bleeding. Conservative management was successfully employed, avoiding surgical intervention. This case underscores the need for vigilance when administering G-CSF, particularly in patients at high risk for complications, and contributes to the limited body of literature on G-CSF-induced splenic infarction.
• Krishnadasan, R., Nematollahi, S., & Acharya, U. (2015). "ATRA-Induced bone Marrow Necrosis in a Patient with Acute Promyelocytic Leukemia. A Case Presentation and Review of the Literature.". American Journal of Hematology/Oncology, 11(5).
• Zeidan, A. M., Borate, U., Pollyea, D. A., Brunner, A. M., Roncolato, F., Garcia, J. S., Filshie, R., Odenike, O., Watson, A. M., Krishnadasan, R., Bajel, A., Naqvi, K., Zha, J., Cheng, W. H., Zhou, Y., Hoffman, D., Harb, J. G., Potluri, J., & Garcia-Manero, G. (2023). A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. American journal of hematology, 98(2), 272-281.
  More info

  Patients with relapsed/refractory (R/R) higher-risk myelodysplastic syndromes (MDS) have a dismal median overall survival (OS) after failing hypomethylating agent (HMA) treatment. There is no standard of care for patients after HMA therapy failure; hence, there is a critical need for effective therapeutic strategies. Herein, we present the safety and efficacy of venetoclax + azacitidine in patients with R/R MDS. This phase 1b, open-label, multicenter study enrolled patients ≥18 years. Patients were treated with escalating doses of oral venetoclax: 100, 200, or 400 mg daily for 14 days every 28-day cycle. Azacitidine was administered on Days 1-7 every cycle at 75 mg/m /day intravenously/subcutaneously. Responses were assessed per modified 2006 International Working Group (IWG) criteria. Forty-four patients (male 86%, median age 74 years) received venetoclax + azacitidine treatment. Median follow-up was 21.2 months. Hematological adverse events of Grade ≥ 3 included febrile neutropenia (34%), thrombocytopenia (32%), neutropenia (27%), and anemia (18%). Pneumonia (23%) was the most common Grade ≥ 3 infection. Marrow responses were seen including complete remission (CR, n = 3, 7%) and marrow CR (mCR, n = 14, 32%); 36% (16/44) achieved transfusion independence (TI) for RBCs and/or platelets, and 43% (6/14) with mCR achieved hematological improvement (HI). The median time to CR/mCR was 1.2 months, and the median duration of response for CR + mCR was 8.6 months. Median OS was 12.6 months. Venetoclax + azacitidine shows activity in patients with R/R MDS following prior HMA therapy failure and provides clinically meaningful benefits, including HI and TI, and encouraging OS.
• Krishnadasan, R., Zeidan, A. M., Borate, U., Pollyea, D. A., Brunner, A. M., Roncolato, F., Garcia, J. S., Filshie, R., Odenike, O., Watson, A. M., Bajel, A., Naqvi, K., Zha, J., Cheng, W., Zhou, Y., Hoffman, D., Harb, J. G., Potluri, J., & Garcia‐Manero, G. (2022). A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. American Journal of Hematology, 98(2), 272-281. doi:10.1002/ajh.26771
• Krishnadasan, R. (2021). Hemolytic Anemias: Autoimmune and Beyond. Journal of the advanced practitioner in oncology, 12(3), 337-340.
  More info

  During JADPRO Live Virtual 2020, Ravi Krishnadasan, MD, FACP, provided an overview of the terminology of hemolysis, laboratory tests used in the diagnosis of hemolytic anemias, and appropriate indications for treatment of the various hemolytic anemias.
• McBride, A., Campen, C. J., Camamo, J., Maloney, M., Persky, D., Kurtin, S. E., Barket, N. L., Krishnadasan, R., Elquza, E., Anwer, F., & Weibel, K. (2018). Implementation of a pharmacy-managed program for the transition of chemotherapy to the outpatient setting. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 75(9), e246-e258.
  More info

  Implementation of a pharmacy-managed program for the transition of chemotherapy to the outpatient setting is described.
• Chan, O., Chen, H., Krishnadasan, R., & Anwer, F. (2016). Case of relentless chronic phase of chronic myeloid leukaemia. BMJ case reports, 2016.
  More info

  Initial treatment of chronic phase chronic myeloid leukaemia is straightforward in today's era of tyrosine kinase inhibitors. However, managing refractory cases remain a major challenge due to the multiple factors that can influence decision-making, including medication tolerance, disease burden, mutation status, comorbidities, availability of donor, and fitness for an ablative conditioning. We report a male patient presenting with chronic phase chronic myeloid leukaemia who was treated with 5 different tyrosine kinase inhibitors either due to intolerance and/or failed response. He subsequently received 2 haploidentical haematopoietic stem cells transplants before achieving complete remission. This case highlights various treatment options, need for vigilant disease monitoring, and the possibility of complete positive response even after many lines of therapy failure.
• Diri, R., Anwer, F., Yeager, A., Krishnadasan, R., & McBride, A. (2016). Retrospective review of intravenous pentamidine for Pneumocystis pneumonia prophylaxis in allogeneic hematopoietic stem cell transplantation. Transplant infectious disease : an official journal of the Transplantation Society, 18(1), 63-9.
  More info

  Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of numerous opportunistic infections. Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that can develop in immunocompromised individuals. Current prophylaxis for PJP includes trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, atovaquone, or inhaled pentamidine (PEN), often with varying breakthrough rates. The use of intravenous (IV) PEN for PJP prophylaxis has been evaluated in pediatric patients.
• Krishnadasan, R. (2016). Diagnosis and Treatment of Benign Bleeding Disorders. Journal of the advanced practitioner in oncology, 7(3), 327.
• Krishnadasan, R., Abraham, I., Campen, C., Chalasani, P., Diri, R., & Mcbride, A. (2016). Evaluation of Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism for Inherited Thrombophilia Disorders. Blood, 128(22), 5007-5007. doi:10.1182/blood.v128.22.5007.5007
  More info

  Background Venous thromboembolism can be classified according to the presence of either environmental or genetic risk factors. Risk factors for thrombosis can include activated protein C resistance, and heritable including deficiencies of antithrombin, protein C or protein S. Factor V Leiden deficiency and prothrombin gene mutations are some of the more common thrombophilias, with a slight increased risk for venous thromboembolism (VTE). Current guidelines suggest the use of low-molecular weight heparins for secondary prophylaxis in patients with VTE. However, there is a lack of data on the use of Direct Oral Anticoagulant (DOACs) in patients with inherited thrombophilia. We evaluated our use of rivaroxaban in patients with thrombophilia disorders treated for secondary DVT prophylaxis. Method We performed a retrospective evaluation of patients in our institution with inherited thrombophilia with an active VTE diagnosis who received DOACs for secondary prophylaxis from November 2013 until April 2016. Data collected included patient demographics, inherited thrombophilia mutation, previous history of VTE, prior treatments, and efficacy and safety of anticoagulation with DOACs. Results We had 13 patients with inherited thrombophilia mutation and 4 patients diagnosed with concomitant cancer (non-Hodgkin lymphoma, melanoma, and 2 with breast cancer) (Table 1). Out of 13 patients 3 failed warfarin, and one failed fondaparinux prior to switching to a DOAC. Mutation with heterozygous Factor V Leiden deficiency was reported in 7 patients, while mutations with Protein C and/or S deficiency were found in 4 patients. One patient had both Factor V Leiden and Protein C deficiency mutations. The prothrombin gene mutation was identified in one patient. The median of length of therapy was 2 years with 8/13 still on rivaroxaban in April 2016. The shortest treatment duration was 41 days for a patient who failed rivaroxaban with a second clot and was switched to apixaban without subsequent treatment failure. Two patients experienced 4 non-major episodes of gastrointestinal bleeding, nose bleeding and dark stool. One patient developed rash with noted bruising during their rivaroxaban therapy. Conclusion: This is the first report on outcomes for secondary DVT prophylaxis with DOACs in patients with underlying thrombophilia mutations. Safety and efficacy of DOACs for secondary VTE prophylaxis yielded favorable results; however, future prospective studies in the setting of thrombophilia are warranted. Disclosures McBride:Sanofi: Research Funding.
• Diri, R., Anwer, F., Yeager, A., Krishnadasan, R., & McBride, A. (2015). Retrospective review of intravenous pentamidine for Pneumocystis pneumonia prophylaxis in allogeneic hematopoietic stem cell transplantation. Transplant Infectious Disease.
• Diri, R., McBride, A., Yeager, A. M., Anwer, F., & Krishnadasan, R. (2015). Retrospective Review of Intravenous Pentamidine for Pneumocystis Pneumonia Prophylaxis in Patients Undergoing Hematopoietic Stem Cell Transplantation. Biology of Blood and Marrow Transplant, 21, S367.
• Nematollahi, S., Acharya, U. H., & Krishnadasan, R. (2015). ATRA-Associated Marrow Necrosis in a Patient With Acute Promyelocytic Leukemia: A Case Presentation and Review of the Literature. American Journal of Hematology/Oncology{\textregistered}, 11.
• Brown, G. E., Babiker, H. M., Cantu, C. L., Yeager, A. M., & Krishnadasan, R. (2014). "Almost bleeding to death": the conundrum of acquired amegakaryocytic thrombocytopenia. Case reports in hematology, 2014, 806541.
  More info

  Acquired amegakaryocytic thrombocytopenia (AAT) is a rare hematological disorder causing severe thrombocytopenia and bleeding. Previous in vitro studies postulated both cell-mediated suppression of megakaryocytopoiesis in early megakaryocytic progenitor cells and humoral-mediated suppression by anti-thrombopoietin antibodies as possible etiologies of AAT. Patients with AAT usually present with severe bleeding and thrombocytopenia that is unresponsive to steroids and intravenous immunoglobulin (IVIG). Although standard guidelines have not been established for management of AAT, a few case reports have indicated a response to immunosuppressive treatment. The prompt recognition of this disease entity is essential in view of the substantial risk of morbidity and mortality from excessive bleeding. We report a case of AAT successfully treated with equine antithymocyte globulin (ATG) and cyclosporine (CSP).
• Rogowitz, E., Babiker, H. M., Krishnadasan, R., Jokerst, C., Miller, T. P., & Bookman, M. (2013). Heart of lymphoma: primary mediastinal large B-cell lymphoma with endomyocardial involvement. Case reports in oncological medicine, 2013, 814291.
  More info

  Primary mediastinal B-cell lymphoma (PMBCL) is an uncommon aggressive subset of diffuse large B-cell lymphomas. Although PMBCL frequently spreads locally from the thymus into the pleura or pericardium, it rarely invades directly through the heart. Herein, we report a case of a young Mexican female diagnosed with PMBCL with clear infiltration of lymphoma through the cardiac wall and into the right atrium and tricuspid valve leading to tricuspid regurgitation. This was demonstrated by cardiac MRI and transthoracic echocardiogram. In addition, cardiac MRI and CT scan of the chest revealed the large mediastinal mass completely surrounding and eroding into the superior vena cava (SVC) wall causing a collar of stokes. The cardiac and SVC infiltration created a significant therapeutic challenge as lymphomas are very responsive to chemotherapy, and treatment could potentially lead to vascular wall rupture and hemorrhage. Despite the lack of conclusive data on chemotherapy-induced hemodynamic compromise in such scenarios, her progressive severe SVC syndrome and respiratory distress necessitated urgent intervention. In addition to the unique presentation of this rare lymphoma, our case report highlights the safety of R-CHOP treatment.
• Krishnadasan, R., Bifulco, C., Kim, J., Rodov, S., Zieske, A. W., & Vanasse, G. J. (2006). Overexpression of SOCS3 is associated with decreased survival in a cohort of patients with de novo follicular lymphoma. British journal of haematology, 135(1), 72-5.
  More info

  The prognostic significance of SOCS3 protein expression was determined in de novo follicular lymphomas (FL) with t(14;18) and bcl-2 overexpression. Presentation lymph nodes from 82 FL patients for whom clinical information was available were immunohistochemically segregated into SOCS3-positive (n = 42) or -negative (n = 40) cohorts, and overall survival (OS) was analysed. SOCS3-positive FL patients had a median OS of 10 years compared with 22 years in SOCS3-negative patients (P = 0.001, log rank test). After adjusting for Follicular Lymphoma International Prognostic Index subgroups, SOCS3 overexpression remained an independent predictor of decreased OS (P < 0.001). These findings suggest that overexpression of SOCS3 may be an independent poor prognostic variable in patients with de novo FL.
• Barrientos, J. C., Kim, J., Krishnadasan, R., Rodov, S., & Vanasse, K. G. (2005). Bcl2 Associated Induction of the Suppressor of Cytokine Signaling-3 (SOCS3) Gene Involves Activation of the p44/42 MAPK Pathway.. Blood, 106(11), 2286-2286. doi:10.1182/blood.v106.11.2286.2286
  More info

  SOCS3 has been shown to be an essential regulator of IL-6 signaling in hepatocytes and macrophages, as well as a negative regulator of G-CSF signaling in myeloid cells, and SOCS3 expression appears to be STAT3-dependent. However, the underlying cellular pathways which regulate SOCS3 expression in B cells remain to be clearly defined. We previously showed that polyclonal CD19+ B cells isolated from Bcl2 overexpressing Eμ-Bcl2 transgenic mice overexpress SOCS3 protein and that exogenous expression of Bcl2 in hematopoietic and fibroblast cell lines induces SOCS3 protein expression. We also found that a distinct subset of follicular lymphomas (FL) exhibit combined overexpression of Bcl2 and SOCS3. We hypothesized that Bcl2-mediated induction of SOCS3 in B cells may occur indirectly via deregulation of Bcl2-associated cell signaling pathways. In the current study, IL-3-dependent BaF3 pro-B cells were stably transduced with either a 717bp human Bcl2α cDNA (BaF3/Bcl2) or vector only control (Baf3Δ). Cell lines were initially grown in the presence of IL-3, with IL-3 removed 48 hours prior to protein measurements. Western analysis using Bcl2 antisera revealed high level Bcl2 expression in transduced cells (BaF3/Bcl2) and absence of Bcl2 in BaF3Δ control cells. When probed with SOCS3 antisera, BaF3/Bcl2 cells exhibited marked overexpression of SOCS3 protein whereas BaF3Δ control cells did not express SOCS3. To assess whether Bcl2-associated induction of SOCS3 is STAT3-dependent, we measured phospho-STAT3 levels relative to STAT3 in BaF3/Bcl2 cells. Interestingly, when probed with phospho-STAT3 and STAT3 antisera, BaF3/Bcl2 and BaF3Δ cells did not reveal phospho-STAT3 protein but revealed equivalent STAT3 protein levels. Since we had previously noted overexpression of p44/42 Map kinase (MAPK) in CD19+ B cells from Eμ-Bcl2 transgenic mice relative to littermate controls, we next wanted to determine whether p44/42MAPK signaling played a role in Bcl2-mediated SOCS3 induction. Western analysis using p44/42MAPK antisera revealed overexpression of p44/42MAPK in BaF3/Bcl2 cells relative to BaF3Δ control cells. BaF3/Bcl2 and BaF3Δ cells were then grown in the presence or absence of a specific p44/42MAPK pathway inhibitor (MEK 1/2 inhibitor U0126), and whole cell lysates were analyzed for SOCS3 expression by Western analysis. When probed with SOCS3 antisera, BaF3/Bcl2 cells selectively grown in the presence of the p44/42MAPK inhibitor revealed complete abrogation of SOCS3 protein expression while those grown in the absence of inhibitor continued to harbor SOCS3 protein. As expected, ERK1/2 protein levels were selectively decreased in response to treatment with the p44/42MAPK inhibitor, indicating specific inhibition of the p44/42MAPK pathway. Bcl2 protein levels in BaF3/Bcl2 cells remained unchanged in the presence or absence of the p44/42MAPK inhibitor. As controls, inhibitors of p38MAPK (SB203580), AKT (Triciribine), and PI3K (LY294002) were evaluated and none were found to affect SOCS3 protein levels in BaF3/Bcl2 cells. These data indicate that Bcl2-associated induction of SOCS3 in B cells involves activation of the p44/42MAPK cell signaling pathway and is independent of STAT3 activation. These studies illustrate a novel and previously unappreciated Bcl2-associated signaling pathway involving SOCS3 induction in B cells that may play an important role in B cell biology and in Bcl2-associated hematologic malignancies.
• Bifulco, C., Kim, J., Krishnadasan, R., Rodov, S., & Vanasse, K. G. (2005). Combined Overexpression of Bcl-2 and SOCS3 Is Associated with Decreased Survival in a Cohort of Patients with De Novo Follicular Lymphoma.. Blood, 106(11), 989-989. doi:10.1182/blood.v106.11.989.989
  More info

  Follicular lymphomas (FL) comprise approximately twenty-five percent of all cases of non-Hodgkin’s lymphomas (NHL) in humans and are marked by a highly variable clinical course, ranging from indolent to rapidly progressive disease. The genetic hallmark of FL is t(14;18), resulting in deregulated expression of Bcl-2 and abrogation of the majority of apoptotic pathways in B and T lymphocytes. Data suggest that while t(14;18) is sufficient to initiate an oncogenic pathway, Bcl-2 alone is a relatively weak oncogene and requires additional cooperating genetic lesions for neoplastic transformation to occur. We previously demonstrated that Bcl-2 overexpression is associated with overexpression of the suppressor of cytokine signaling-3 (SOCS3) gene in a group of patients with de novo FL. In the current study, to determine whether SOCS3 overexpression has prognostic significance in FL, we performed a retrospective cohort study utilizing de novo FL lymph node tissue banked at Yale University. Eligibility criteria included subjects with FL tissue diagnosed as either histologic Grades I or II and harboring t(14;18)+. Subjects with transformed FL at presentation, HIV, other malignancy, or chronic autoimmune disorders were excluded. Subjects were segregated into two cohorts based on standard immunohistochemistry using SOCS3 and Bcl-2 antisera on FL tissue: Cohort 1 harboring combined overexpression of Bcl-2 and SOCS3 within the follicular center cell region and Cohort 2 harboring sole overexpression of Bcl-2. Immunostaining of germinal center B cells from benign hyperplastic tonsil tissue was used as a negative control for SOCS3 and Bcl-2 expression. Medical record review was performed to determine survival time from the date of initial diagnosis and to calculate the Follicular Lymphoma International Prognostic Index (FLIPI). Eighty-two subjects met eligibility criteria and had medical records available for review. Of these, 42 overexpressed both Bcl-2 and SOCS3 and 40 expressed Bcl-2 alone. Median survival in Cohort 1 was 8 years (95% CI 3.68, 12.32) compared to a median survival of 16.5 years (95% CI 14.56, 20.44) for Cohort 2 (Kaplan Meier survival analysis; p=0.01 log rank test). FLIPI score was not significantly different between the two cohorts. The decrease in survival in Cohort 1 (harboring combined overexpression of Bcl-2 and SOC3) remained statistically significant after adjustment for the FLIPI score (Cox Regression Analysis, p=0.01). Transformation to high grade NHL occurred in 8 of 42 (19%) and 2 of 40 (5%) subjects in Cohort 1 and Cohort 2, respectively (p =0.05, Chi Square Test). This large retrospective cohort study demonstrates that FL harboring combined overexpression of Bcl-2 and SOCS3 was associated with an approximately 50% reduction in survival from the time of diagnosis as compared to subjects with FL marked by overexpression of Bcl-2 alone. This effect was independent of the FLIPI score. These findings suggest that overexpression of SOCS3 protein may be a poor prognostic factor in patients with de novo FL. Further studies will examine whether combined overexpression of Bcl-2 and SOCS3 results in deregulation of cellular pathways which portend a more aggressive natural history of follicular lymphoma.

Case Studies

• Krishnadasan, R., Anwer, F., Yun, S., Nair, A., Ahmad, Y., & Deeg, H. (2015. Severe refractory immune thrombocytopenia successfully treated with high-dose pulse cyclophosphamide and eltrombopag(p. 4).
• Peel, C., Peel, C., Crawford, C., Crawford, C., Sisti, G., Sisti, G., Amaraneni, A., Amaraneni, A., Krishnadasan, R., Krishnadasan, R., Coppola, L., Coppola, L., Jain, J., & Jain, J. (2024. Glanzmann's Thrombasthenia During Pregnancy(pp Pending).