- Email: [email protected]
Identification of a Novel Regulator of AML
Abstracts between 2000 and 2015. Patients: 23 cases of BPDCN identified between 2000 and 2015 via the MSKCC pathology database. Main Outcome Measures: Demographics, clinical presentation, staging, treatment, response to treatment, and outcomes. Results: 23 patients (18 male, 5 female) were seen at MSKCC. Median age was 65. Twenty-one had stage IV disease (8 skin only, 12 bone marrow, 2 peripheral blood). Twelve had IPI of 3. Patients were not treated in a standard fashion. Most were treated initially with curative intent with: ICE (n¼4), HyperCVAD (n¼4), HiDAC (n¼2), SMILE (n¼1), IVAC (n¼1), EPOCH (n¼1), and NY II Pediatrics Regimen (n¼1). Ten were consolidated with either autologous (n¼3) or allogenic (n¼7) stem cell transplantation. Elderly/frail patients were treated initially with: pralatrexate (n¼3), gemcitabine (n¼2), radiation (n¼2), and alemtuzumab (n¼1). One was lost to follow up. Median overall survival was not reached (12 alive) and median event free survival was 16.6 months with a median duration of follow up of 24.7 months. Of patients treated with combination chemotherapy, median OS was not reached (9 alive) and median EFS was 23.3 months. Seven remain in continuous complete remission (CCR) at a median of 34 months. Eight received pralatrexate (3 initial; 5 relapse). Median age was 77. The ORR to pralatrexate was 75% (6/8). Complete and partial response were seen in 4 (50%) and 2 (25%) patients respectively. The median duration of response was 4.8 months (range 2.5-8.7 months). Conclusions: BPDCN is an aggressive neoplasm often treated with combination chemotherapy with consolidation with transplantation. With such approaches 50% of our patients are in CCR. Our series shows that pralatrexate is active in BPCDN. Further studies to better define the activity of pralatrexate in this rare disease are warranted. Keywords: Blastic plasmacytoid dendritic cell neoplasm, BPDCN, CD4+/CD56+ hematodermic neoplasm, blastic natural killer cell lymphoma, pralatrexate.
Research Topics
1000 The first analysis of quality of life of patients with acute leukemia in Republic of Armenia Yervand K. Hakobyan1 1
Hematology Center after prof. Yeolyan MH RA
Objective: Since hematological cases can be treated and prolongation of life is achieved, many different spirituals and psychological concerns must be addressed to maintain smooth functioning and optimize quality of life (QoL). This research study has been designed the first time to place into hematological practice in Armenia. Design: QoL questionnaire include common and disease related specific problems: over 50 questions about psychological and functional conditions. The questionnaires were first filled out within the 7 days after admittance and after two weeks. Main Outcomes Measures and Results: The study of questionnaires revealed that weakness impaired the patients’ QoL in 80% (n¼64), the bone pain e in 85% (n¼ 68), fever- in 75% (n¼60), dyspepsia e in 60% (n¼48), followed by the decreased ability to work e in 60% (n¼48) and lower personal relations e in 62.5% (n¼50) of cases. QoL indicators were dependant on the disease diversity and accompanied risk factors. Patients with high-risk and AML have shown the poorer indicators of QoL then the patients with low-risk and ALL. Acknowledgment and understanding by the patients, that many of side effects and spiritual feelings are impermanent and predictable, may create sense of confidence. Our research data indicates that patients in general trust and are confident in their healthcare practitioners (physicians and nurses). They do also have disclosed the chemotherapy treatment as quite a sensitive financial burden for them. 90% (n¼ 72) of all patients pointed out their families, friends and fellows as supportive factors. As it’s been shown, the side effects of chemotherapy and other cancer-related issues are the most influential factors to decrease the QoL of patients with AL. Conclusions: The first step towards dealing with the routine chemotherapy treatment is communication. The second step is QoL information: perception that many of depressive feelings are predictable and not fatal, and many of side effects are impermanent, may become meaningful. The modified QoL questionnaire for the patients with AL is one of the well-validated instruments to place into everyday practice to obtain reliable scores and meaningful data on QoL and it should become an integral part in AL treatment decision-making.
1001 Identification of a Novel Regulator of AML Miguel Gallardo, PhD,1 Hun Ju Lee, MD,2 Xiaorui Zhang,1 Laura Pageon, DVMS,3 Asha Multani, PhD,4 Carlos Bueso-Ramos, MD, PhD,5 Steven Kornblau, MD,1 Sean M. Post, PhD1
Clinical Lymphoma, Myeloma & Leukemia September 2015
- S75
Abstracts 1
Department of Leukemia, University of Texas MD Anderson Cancer
Center, Houston, TX 77030, USA; 2Department of Lymphoma, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; 3Department of Veterinary Medicine & Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; 4
Department of Genetics, University of Texas MD Anderson Cancer
Center, Houston, TX 77030, USA; 5Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
The past several decades have seen little progress in the development of targeted treatments for AML patients. This is due in large part to our limited understanding of how recurrent genetic alterations truly impact disease progression. Thus, there is a great need to identify novel genetic alterations that drive AML and establish a mechanistic understanding of how these changes influence disease progression. Through this, we can develop personalized therapeutic approaches for patients with these alterations. Recently, The Cancer Genome Atlas identified mutations in HNRNP K that potentially contribute to AML progression. Additionally, several clinical studies have shown that HNRNP K is one of six genes mapped to the 9q21.32 locus, which is lost in a subset of AML patients. Together, these findings suggest hnRNP K may serve as a currently uncharacterized tumor suppressor and that its haploinsufficiency plays a pivotal role in AML progression. Mechanistically, hnRNP K functions as a DNA and RNA binding protein that transcriptionally and translationally governs gene expression. To examine potential hnRNP K tumor suppressive activities in vivo, we generated a haploinsufficient hnRNP K mouse model. hnRNP K haploinsufficiency resulted in reduced survival, increased tumor formation, genomic instability, and the development of transplantable hematopoietic neoplasms with extensive myeloproliferation through ablation of proliferation and differentiation programs. These data implicate hnRNP K loss in the development of hematological disorders and suggest hnRNP K is a bona fide tumor suppressor.
1003
1002
Hematologic Oncology Chemotherapy Stewardship Program: A One Year Institutional Experience
Secondary Hemophagocytic Lymphohistiocytoisis (HLH) in Adults Patients 1
1
1
Gevorg Tamamyan, Hagop Kantarjian, Koji Sasaki, Kenneth McClain,3 Carl Allen,3 Sherry Pierce,1 Jorge Cortes,1 Marina Konopleva,1 Guillermo Garcia-Manero,1 Michael Rytting,1 Nitin Jain,1 Waleed Abdellal,1 Sergej Konoplev,2 Naval Daver1 1
Department of Leukemia, MD Anderson Cancer Center; 2Depart-
ment of Hematopathology, MD Anderson Cancer Center; 3Histiocytosis Program, Texas Children’s Cancer Center, Texas Children’s Hospital
Purpose: Secondary hemophagocytic lymphohistiocytosis in adults is a lethal and often under diagnosed disorder. The underlying etiology and clinical manifestations of secondary HLH in adult populations is less well defined than pediatric populations.
S76
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Methods: The MDACC pathology database (1991-2014) was broadly interrogated for the keywords “hemophagocytosis” and/or “lymphohistiocytosis”. 88 patients were identified. 11 patients <18 years and 7 patients with insufficient documentation were excluded. The remaining 70 patients were retrospectively reviewed. Results: Among the 70 patients identified, 53 had pathologist confirmed hemophagocytosis in the bone marrow and/or lymph node/spleen. Sixteen patients met the HLH-2004 diagnostic criteria. An additional 7 patients fulfilled 4 criteria but lacked the requisite fifth criteria to confirm HLH. The 16 adult patients [median (med) age 43; range 1877] included 11 males and 69% were Caucasian. At diagnosis, among evaluable patients 80%(12/15) had fever; 66.7%(10/15) had splenomegaly; 82%(13/16) had bi- or pancytopenia; 62.5% (10/16) had a ferritin level >10,000 and 37.5% had a ferritin level >50,000(med ferritin ¼ 5,202ng/mL; range 665 e 60,761); 68.75%(11/16) had coagulopathy; 56.25%(9/16) had lactate dehydrogenase elevation >2.5 times; 38%(5/13) had a fibrinogen level below 200 mg/dL (med 266; range 78-616); 92.86%(13/14) had elevated triglycerides (med 288.5mg/dL; range 105 - 599), and 81.81%(9/11) had elevated soluble interleukine-2 receptor level (med 3883pg/mL, range 35 - 39100). Among the 16 HLH cases 13 patients (81%) had associated hematologic malignancy: 7 non-Hodgkin’s lymphoma, 2 AML; 1 CMML; 1 CLL, 1 patient who developed AML 3 months after, and 1 who developed aplastic anemia 4 months after HLH diagnosis. The remaining 3 cases had infection associated HLH: aspergillus, EBV and unknown. 13/16 (81%) of patients received HLH directed therapy comprising high dose steroids, etoposide, cyclosporine and supportive care. 12/16 (75%) patients have died. The median survival for all patients was 2.3 months (range 5 days e 40 months). Conclusion: A number of patients with pathologic evidence of hemophagocytosis had incomplete work-up to confirm or refute HLH. Secondary HLH was frequently associated with hematological malignancies, but not with solid tumors in our database. Improved identification and therapy in adult HLH is warranted.
Clinical Lymphoma, Myeloma & Leukemia September 2015
Amir Steinberg, MD,1 Damaris Peralta-Hernandez, RPh,1 Sara Kim, RPh,1 Talaat Aggour, BS1 1
Mount Sinai Hospital, New York City, New York, USA
Introduction: Antibiotics stewardship has become an integral aspect of ID management, limiting potential for future resistance while factoring cost. One must factor whether therapy in the ambulatory setting is less costly or formulary status impacts cost. No “chemotherapy” stewardship program has been described in a review of the literature. We report the first such description of a program, while focusing on hematologic malignancies. Methods: Specialist in hematologic-oncology was designated to answer communication for requests for use of non-formulary chemotherapeutic agents and decide on drug approval. This was then communicated to oncology pharmacists.
Research Topics
1000 The first analysis of quality of life of patients with acute leukemia in Republic of Armenia Yervand K. Hakobyan1 1
Hematology Center after prof. Yeolyan MH RA
Objective: Since hematological cases can be treated and prolongation of life is achieved, many different spirituals and psychological concerns must be addressed to maintain smooth functioning and optimize quality of life (QoL). This research study has been designed the first time to place into hematological practice in Armenia. Design: QoL questionnaire include common and disease related specific problems: over 50 questions about psychological and functional conditions. The questionnaires were first filled out within the 7 days after admittance and after two weeks. Main Outcomes Measures and Results: The study of questionnaires revealed that weakness impaired the patients’ QoL in 80% (n¼64), the bone pain e in 85% (n¼ 68), fever- in 75% (n¼60), dyspepsia e in 60% (n¼48), followed by the decreased ability to work e in 60% (n¼48) and lower personal relations e in 62.5% (n¼50) of cases. QoL indicators were dependant on the disease diversity and accompanied risk factors. Patients with high-risk and AML have shown the poorer indicators of QoL then the patients with low-risk and ALL. Acknowledgment and understanding by the patients, that many of side effects and spiritual feelings are impermanent and predictable, may create sense of confidence. Our research data indicates that patients in general trust and are confident in their healthcare practitioners (physicians and nurses). They do also have disclosed the chemotherapy treatment as quite a sensitive financial burden for them. 90% (n¼ 72) of all patients pointed out their families, friends and fellows as supportive factors. As it’s been shown, the side effects of chemotherapy and other cancer-related issues are the most influential factors to decrease the QoL of patients with AL. Conclusions: The first step towards dealing with the routine chemotherapy treatment is communication. The second step is QoL information: perception that many of depressive feelings are predictable and not fatal, and many of side effects are impermanent, may become meaningful. The modified QoL questionnaire for the patients with AL is one of the well-validated instruments to place into everyday practice to obtain reliable scores and meaningful data on QoL and it should become an integral part in AL treatment decision-making.
1001 Identification of a Novel Regulator of AML Miguel Gallardo, PhD,1 Hun Ju Lee, MD,2 Xiaorui Zhang,1 Laura Pageon, DVMS,3 Asha Multani, PhD,4 Carlos Bueso-Ramos, MD, PhD,5 Steven Kornblau, MD,1 Sean M. Post, PhD1
Clinical Lymphoma, Myeloma & Leukemia September 2015
- S75
Abstracts 1
Department of Leukemia, University of Texas MD Anderson Cancer
Center, Houston, TX 77030, USA; 2Department of Lymphoma, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; 3Department of Veterinary Medicine & Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; 4
Department of Genetics, University of Texas MD Anderson Cancer
Center, Houston, TX 77030, USA; 5Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
The past several decades have seen little progress in the development of targeted treatments for AML patients. This is due in large part to our limited understanding of how recurrent genetic alterations truly impact disease progression. Thus, there is a great need to identify novel genetic alterations that drive AML and establish a mechanistic understanding of how these changes influence disease progression. Through this, we can develop personalized therapeutic approaches for patients with these alterations. Recently, The Cancer Genome Atlas identified mutations in HNRNP K that potentially contribute to AML progression. Additionally, several clinical studies have shown that HNRNP K is one of six genes mapped to the 9q21.32 locus, which is lost in a subset of AML patients. Together, these findings suggest hnRNP K may serve as a currently uncharacterized tumor suppressor and that its haploinsufficiency plays a pivotal role in AML progression. Mechanistically, hnRNP K functions as a DNA and RNA binding protein that transcriptionally and translationally governs gene expression. To examine potential hnRNP K tumor suppressive activities in vivo, we generated a haploinsufficient hnRNP K mouse model. hnRNP K haploinsufficiency resulted in reduced survival, increased tumor formation, genomic instability, and the development of transplantable hematopoietic neoplasms with extensive myeloproliferation through ablation of proliferation and differentiation programs. These data implicate hnRNP K loss in the development of hematological disorders and suggest hnRNP K is a bona fide tumor suppressor.
1003
1002
Hematologic Oncology Chemotherapy Stewardship Program: A One Year Institutional Experience
Secondary Hemophagocytic Lymphohistiocytoisis (HLH) in Adults Patients 1
1
1
Gevorg Tamamyan, Hagop Kantarjian, Koji Sasaki, Kenneth McClain,3 Carl Allen,3 Sherry Pierce,1 Jorge Cortes,1 Marina Konopleva,1 Guillermo Garcia-Manero,1 Michael Rytting,1 Nitin Jain,1 Waleed Abdellal,1 Sergej Konoplev,2 Naval Daver1 1
Department of Leukemia, MD Anderson Cancer Center; 2Depart-
ment of Hematopathology, MD Anderson Cancer Center; 3Histiocytosis Program, Texas Children’s Cancer Center, Texas Children’s Hospital
Purpose: Secondary hemophagocytic lymphohistiocytosis in adults is a lethal and often under diagnosed disorder. The underlying etiology and clinical manifestations of secondary HLH in adult populations is less well defined than pediatric populations.
S76
-
Methods: The MDACC pathology database (1991-2014) was broadly interrogated for the keywords “hemophagocytosis” and/or “lymphohistiocytosis”. 88 patients were identified. 11 patients <18 years and 7 patients with insufficient documentation were excluded. The remaining 70 patients were retrospectively reviewed. Results: Among the 70 patients identified, 53 had pathologist confirmed hemophagocytosis in the bone marrow and/or lymph node/spleen. Sixteen patients met the HLH-2004 diagnostic criteria. An additional 7 patients fulfilled 4 criteria but lacked the requisite fifth criteria to confirm HLH. The 16 adult patients [median (med) age 43; range 1877] included 11 males and 69% were Caucasian. At diagnosis, among evaluable patients 80%(12/15) had fever; 66.7%(10/15) had splenomegaly; 82%(13/16) had bi- or pancytopenia; 62.5% (10/16) had a ferritin level >10,000 and 37.5% had a ferritin level >50,000(med ferritin ¼ 5,202ng/mL; range 665 e 60,761); 68.75%(11/16) had coagulopathy; 56.25%(9/16) had lactate dehydrogenase elevation >2.5 times; 38%(5/13) had a fibrinogen level below 200 mg/dL (med 266; range 78-616); 92.86%(13/14) had elevated triglycerides (med 288.5mg/dL; range 105 - 599), and 81.81%(9/11) had elevated soluble interleukine-2 receptor level (med 3883pg/mL, range 35 - 39100). Among the 16 HLH cases 13 patients (81%) had associated hematologic malignancy: 7 non-Hodgkin’s lymphoma, 2 AML; 1 CMML; 1 CLL, 1 patient who developed AML 3 months after, and 1 who developed aplastic anemia 4 months after HLH diagnosis. The remaining 3 cases had infection associated HLH: aspergillus, EBV and unknown. 13/16 (81%) of patients received HLH directed therapy comprising high dose steroids, etoposide, cyclosporine and supportive care. 12/16 (75%) patients have died. The median survival for all patients was 2.3 months (range 5 days e 40 months). Conclusion: A number of patients with pathologic evidence of hemophagocytosis had incomplete work-up to confirm or refute HLH. Secondary HLH was frequently associated with hematological malignancies, but not with solid tumors in our database. Improved identification and therapy in adult HLH is warranted.
Clinical Lymphoma, Myeloma & Leukemia September 2015
Amir Steinberg, MD,1 Damaris Peralta-Hernandez, RPh,1 Sara Kim, RPh,1 Talaat Aggour, BS1 1
Mount Sinai Hospital, New York City, New York, USA
Introduction: Antibiotics stewardship has become an integral aspect of ID management, limiting potential for future resistance while factoring cost. One must factor whether therapy in the ambulatory setting is less costly or formulary status impacts cost. No “chemotherapy” stewardship program has been described in a review of the literature. We report the first such description of a program, while focusing on hematologic malignancies. Methods: Specialist in hematologic-oncology was designated to answer communication for requests for use of non-formulary chemotherapeutic agents and decide on drug approval. This was then communicated to oncology pharmacists.