MDS CASE PRESENTATION Rakhi Naik Heme Fellow Aug 3 rd , 2012 THE - PowerPoint PPT Presentation

MDS CASE PRESENTATION Rakhi Naik Heme Fellow Aug 3 rd , 2012

THE CASE  61 y.o. male with long-standing cytopenias since 2007, referred for worsening pancytopenia in the setting of traumatic jaw fracture & osteomyelitis.  Past Medical History:  Severe schizophrenia, moderately controlled on Lamotrigine & Fluphenazine  Hepatitis C infection (genotype 2a, VL 44k, LFTs mildly elevated)  Social History:  Lives with mother who helps with his medications.  Remote history of IV drug abuse and alcoholism, quit in 1971.  Ongoing tobacco use (1 ppd).

COUNT TRENDS Hemoglobin Hemoglobin Platele Plat elets 13 106 130 10.1 11 110 90 9 6.7 70 7 33 50 5 30 2007 2008 2009 2010 2011 2007 2008 2009 2010 2011 ANC ANC 1100 1500 1000 260 ANC 500 0 2007 2008 2009 2010 2011

EVALUATION  Hematology initially consulted in 2010 for mild stable pancytopenia, with hemoglobins in 10-11 g/dL range, platelets in the 80k range, and ANCs slightly downtrending to 700-800.  Given stable disease, cytopenias were thought to be secondary to psychiatric medications + hepatitis C.  In 2011, patient incurred a traumatic jaw fracture requiring ORIF, complicated by coag – Staph/peptostreptococcus bacteremia and osteomyelitis.  Cytopenias persisted after weeks of treatment and jaw debridement (and an AMA discharge)  Eventually consented to a bone marrow, which was performed 1 month after the fracture.

BONE MARROW  1 st bone marrow lost in accessioning!  2 nd bone marrow (performed on the psych service):  Normocellular marrow (40%)  Megaloblastic changes of erythroid lineage, but no dysplasia in megakaryocytes or neutrophils  Polyclonal plasma cell predominance (10-20%)  Impression: Non-specific findings, could be secondary to hepatitis C. Consider vitamin B12 deficiency. B12 level 529.  Other studies:  Flow: Mixed population, slightly abnormal myeloid maturation, no increase in blasts.  Cytogenetics: Lost (again!)  FISH: 7q d deletion i in 3 32.5% o of n nuclei, trisomy 8 in 2.0%

QUESTIONS  What do the bone marrow findings suggest about the etiology of his pancytopenia?  What are his treatment options?  What is his prognosis?

OUR MANAGEMENT  Lamotrigine was switched to Depakote for HDAC properties.  q1-2 week lab visits to establish compliance.  Recently required transfusion of 2 U PRBCs for symptomatic anemia with hemoglobin of 7.1g/dL and was initiated on Darbepoetin.  Scheduled for an initial consultation in Weinberg, but became paranoid about visit and didn’t attend visit despite urging of mother and hematologist.  Initial counts: WBC 1.9, ANC 180, Hemoglobin 9.9, Platelets 53.  Most recent counts: WBC 1.6, ANC 492, Hemoglobin 9.5 (s/p transfusion), Platelets 74.

Classification:  WHO classification of tumours of Haematopoietic and lymphoid tissues, 2008.  2010 ASH Education, Prognosis of Myelodysplastic Syndromes, Guillermo Garcia ‐ Manero  Greenberg P, et al. Blood 1997:89:2079 ‐ 88  Revised International Prognostic Scoring System (IPSS ‐ R) for myelodysplastic syndromes.  Greenberg PL, Tuechler H, Schanz J, et al., Haase D., Blood. 2012 Jun 27. [Epub ahead of print] Mutations:  Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes., Damm F, Kosmider O, Gelsi ‐ Boyer V, et al., Fontenay M;Blood. 2012 Apr 5;119(14):3211 ‐ 8. Epub 2012 Feb 17.  Clinical effect of point mutations in myelodysplastic syndromes., Bejar R, Stevenson K, Abdel ‐ Wahab O, Galili N, et.al., N Engl J Med. 2011 Jun 30;364(26):2496 ‐ 506.  Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts., Papaemmanuil E, Cazzola M, Boultwood J, et al., Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium., N Engl J Med. 2011 Oct 13;365(15):1384 ‐ 95. Epub 2011 Sep 26.  Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A., Jankowska AM, Makishima H, Tiu RV, Szpurka H, Huang Y, Traina F, Visconte V, Sugimoto Y, Prince C, O'Keefe C, Hsi ED, List A, Sekeres MA, Rao A, McDevitt MA, Maciejewski JP., Blood. 2011 Oct 6;118(14):3932 ‐ 41. Monosomal Karyotype:  Five ‐ group cytogenetic risk classification, monosomal karyotype and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS. Deeg HJ, Scott BL, Fang M, et al., Blood. 2012 Jul 5. [Epub ahead of print]  Comparative analysis of the value of allogeneic hematopoietic stem ‐ cell transplantation in acute myeloid leukemia with monosomal karyotype versus other cytogenetic risk categories., Cornelissen JJ, Breems D, van Putten WL, et al,, Löwenberg B., J Clin Oncol. 2012 Jun 10;30(17):2140 ‐ 6. Epub 2012 May 7.  Blood consult: monosomal karyotype acute myeloid leukemia., Garcia JS, Medeiros BC, Appelbaum  Acute myeloid leukemia: the challenge of capturing disease variety., Löwenberg B., Hematology Am Soc Hematol Educ Program. 2008:1 ‐ 11. Review.  Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype., Breems DA, Van Putten WL, De Greef GE, et al., Löwenberg B., J Clin Oncol. 2008 Oct 10;26(29):4791 ‐ 7. Epub 2008 Aug 11. Co ‐ morbidities:  Progosis of MDS, Guillermo Garcia ‐ Manero , ASH Eductational Book , 2010, p330  Co ‐ morbidities and HCT Outcomes, ASH Education Book, 2010, p237