scholarly journals A Case Report of Refractory Immune Thrombocytopenia (ITP) Following Reduced Intensity Conditioning (RIC) Hematopoietic Cell Transplantation (HCT) for Myelodysplastic Syndrome (MDS) Successfully Treated with Off-Label Use of Daratumumab

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4976-4976 ◽  
Author(s):  
Yazan Migdady ◽  
Ridhi Gupta ◽  
Asiri Ediriwickrema ◽  
Francisco Socola ◽  
Sally Arai ◽  
...  
Keyword(s):  
Platelet Count ◽  
Case Report ◽  
Peripheral Blood ◽  
Hematopoietic Cell Transplantation ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Antibody Testing ◽  
Bone Marrow Biopsies

Abstract Background: A source of treatment refractoriness in immune cytopenias appears to be residual CD138/38 positive lymphocyte populations (Audia S et al, Blood 118:4394-400,2011; Mahevas M et al, J Clin Invest 123:432-442, 2013). Persistence of recipient's plasma cells can lead to prolonged refractory thrombocytopenia following RIC-HCT. (Fasano RM et al, Br J Haematol 166(3):425-34, 2014). Daratumumab was effective in the treatment of a child with refractory autoimmune hemolytic anemia after HCT (Tolbert et al, Blood 128:4819, 2016). Case Report: The patient is a 60-year-old man with intermediate-high risk MDS who underwent RIC-HCT with total lymphoid irradiation and antithymocyte globulin with peripheral blood graft from a fully matched unrelated male donor. The patient had mild thrombocytopenia prior to HCT consistent with MDS and had not received platelet transfusions. He had not received any prior therapy for MDS. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. Cytomegalovirus (CMV) serologic testing for exposure was negative for the recipient and positive for the donor. Both the patient and the donor had evidence for prior exposure to Epstein-Barr virus (EBV). He achieved engraftment on day +12. His peripheral blood chimerism on day + 30 showed full donor origin (WB 98%,CD3 96%,CD15 95%, CD19 98%, CD56 95%) and has been maintained to date. Acute skin GVHD responded to corticosteroids. While on corticosteroid therapy, he developed an abrupt decline in platelet count from 156,000/mcl on day +152 to 9, 000/mcl on Day + 166 without evidence for recurrent or active GVHD. While this was initially attributed to simultaneous EBV and CMV reactivations, severe thrombocytopenia persisted after viral clearance. An extensive work up for other etiologies of thrombocytopenia was negative. Repeated bone marrow biopsies were normal, including adequate megakaryocytosis and no MDS recurrence. Platelet associated antibody testing and platelet antigen genotyping were not conclusive for autoimmune versus alloimmune etiology. Testing for platelet HLA antibodies showed calculated Panel Reactive Antibody of 31% and unsatisfactory corrected count increment after transfusion of HLA compatible platelets units. The patient experienced prolonged severe thrombocytopenia for over 26 weeks with platelet count less than 5000/mcl for 22 weeks and only above 10,000 /mcl on 6 occasions. Potentially responsible medications were discontinued serially, but testing for drug inducted ITP was not conducted. Therapy included high dose corticosteroids, high dose immune globulin, rituximab, plasma exchange, splenectomy, romiplostim 10 mcg/kg/week, eltrombopag 100 mg to 150 mg daily for over 24 weeks, and low dose danazol. Fostamatinib was not available. Prednisone dose was tapered over many weeks to 5 mg daily. The patient experienced recurrent life-threatening and vision-threatening bleeding. Cumulative transfusions following Day + 166 were 133 single donor platelet units and 42 red cell units. All products were from CMV negative donors. Eltrombopag and danazol were deemed ineffective and tapered to discontinuation. CD38 positive cells were present in spleen and marrow by immunohistochemistry. Daratumumab 1300 mg was infused weekly x 4. Four weeks after the last dose of daratumumab, his platelet count increased to 91,000/mcl. Platelet count normalized to 150,000/mcl in week 5 or HCT Day + 383. Hypogammaglobulinemia has been the only detectable toxicity. Testing to determine autoimmune versus alloimmune origin is ongoing. Conclusion: Clinical trials of daratumumab for the treatment of severe refractory ITP are indicated. Disclosures No relevant conflicts of interest to declare.

A Case of Clopidogrel Induced TTP Recurring After Four Years

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4678-4678
Author(s):  
Nanda K. Methuku ◽  
Abhinav B. Chandra ◽  
Anuradha Belur ◽  
Lech Dabrowski
Keyword(s):  
Platelet Count ◽  
Renal Insufficiency ◽  
Peripheral Blood ◽  
Blood Smear ◽  
Reticulocyte Count ◽  
Conflicts Of Interest ◽  
Peripheral Blood Smear ◽  
Severe Thrombocytopenia ◽  
Platelet Counts ◽  
Multiple Organs

Abstract Abstract 4678 Case description - A 61 year old woman was started on clopidogrel after having PTCA with stent placement in February 2006. Four weeks after starting clopidogrel she developed thrombocytopenia with platelet nadir of 17,000. Her LDH was 700 IU/L and she was anemic with hemoglobin of 7.4 gm/dl with elevated reticulocyte count. Peripheral blood smear showed schistocytes and diagnosis of TTP secondary to clopidogrel was made. She did not have renal insufficiency. Clopidogrel was discontinued and patient was started on plasmapheresis with recovery of platelet counts. Early attempts in weaning plasmapheresis resulted in drop in platelet count and Rituximab was given to the patient weekly for four weeks. Subsequently, patient was weaned off plasmapheresis. For four years patient was followed periodically with CBC showing platelet counts greater than 250,000. In May 2010, four years after initial event patient was admitted to hospital for abdominal pain and found to have splenic infarcts. Subsequently, she also developed bilateral cerebral infarcts. Platelet count had decreased to less than 100,000. Her LDH was elevated at 419 IU/L. Reticulocyte count was 2.3%. Peripheral blood smear revealed significant number of schistocytes. There was no renal insufficiency or fever. Trans-esophageal echocardiogram (TEE) was done that did not reveal any vegetations. Patient was diagnosed as having recurrence of TTP and started on plasmapheresis with recovery in platelet counts. Pt was also treated with Rituximab. Discussion- We describe a case of TTP initially occurring within weeks of starting clopidogrel. Patient was treated with plasmapheresis and Rituximab and clopidogrel was discontinued. Patient had recurrence after four years as manifested by infarcts in multiple organs, with mild thrombocytopenia, elevated LDH and significant number of schistocytes on peripheral blood smear. It is very uncommon for clopidogrel associated TTP to recur after such a prolonged period of 4 years. Most cases of clopidogrel associated TTP have mild thrombocytopenia. This patient had severe thrombocytopenia on first presentation of TTP but had mild thrombocytopenia on recurrence. This case illustrates the importance of extended follow up and high index of suspicion for TTP as delays in initiation of plasmapheresis has a poor clinical outcome. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Indeterminate Serotonin Release Assays Are Associated with a High Mortality Rate

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-13
Author(s):  
Shawn Jindal ◽  
Christopher Leyton ◽  
Fred Cohen ◽  
Morayma Reyes Gil ◽  
Henny H. Billett
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Clinical Course ◽  
Conflicts Of Interest ◽  
Serotonin Release ◽  
Categorical Variables ◽  
High Dose ◽  
Heparin Binding ◽  
Antibody Testing ◽  
High Concentrations

INTRODUCTION: The serotonin release assay (SRA) is considered the gold standard for diagnosis of heparin-induced thrombocytopenia (HIT). While the SRA holds high sensitivity and specificity when results are definitive, up to 10% of samples from patients with suspected HIT yield "indeterminate" results. In classic HIT, the SRA typically reveals high levels of serotonin release when serum is mixed with low concentrations of heparin and low levels of serotonin release when serum is mixed with high concentrations of heparin. Results are considered "indeterminate" when high levels of serotonin release are seen at both low and high concentrations of heparin, indicating a failure of high-dose heparin to saturate the heparin binding sites of PF4 molecules and inhibit platelet activation. Explanations for indeterminate assays include the presence of heparin-binding proteins that interfere with the assay, high titers of HLA class I alloantibodies, or immune complexes. Since the diagnosis of HIT carries such significance and has so many ramifications, an indeterminate SRA may leave therapeutic indecision. The etiologies, platelet trends, clinical course and outcomes of patients that receive indeterminate SRA results are not well-understood. We conducted a retrospective review of 2,056 patients that underwent SRA testing as part of their evaluation for HIT. METHODS: Using the electronic medical record data extraction software Clinical Looking Glass, we identified patients that underwent SRA testing between 1/1/2014 and 12/31/2018. SRA results were considered "indeterminate" when serotonin release exceeded 19% at all heparin dilutions (0.1 U/mL, 0.5 U/mL and 10 U/mL). We conducted a retrospective chart review to study the clinical course among patients who had "indeterminate" SRA results, the trends in platelet count, the timing of platelet drops and the physician response to this result. Statistical analysis was performed using chi-square testing for categorical variables. RESULTS: We identified 2,056 patients that underwent SRA testing between 2014 and 2019. Of these, 90 patients (4.4%) had "positive" SRA results and 1,814 patients (88.2%) had "negative" SRA results. Among the 152 patients (7.4%) with "indeterminate" SRA results, the mean 4T score was just 2.9, corresponding to a HIT probability of <5%. One-hundred and twenty of these 152 patients (78.9%) had heparin-PF4 antibody testing with optical densities below 0.60 OD, while only 4 of 152 patients (2.6%) had optical densities above 2.00 OD. Seventy eight of 152 patients (51.3%) either continued or were re-exposed to heparin after the indeterminate SRA result, and in 71 of 78 cases (91.0%), the platelet count stabilized or improved despite heparin exposure. In the remaining 7 cases, no acute VTE were found and no diagnosis of HIT was made. Four of the 71 patients (5.6%) that continued or were re-exposed to heparin were noted to have an acute VTE. A significantly higher portion of patients with an indeterminate SRA died during admission compared to those with a positive or negative SRA (49.3% vs. 21.1% and 27.2%, p <2.4 x10-10). The prevalence of thrombocytopenia <50,000 was substantially higher in patients with an indeterminate or positive SRA, compared to those with a negative SRA (39.5% and 40.0% vs. 27.5%, p <4.0 x 10-4). Re-exposure or continuation of heparin did not affect mortality; patients that were given heparin after an indeterminate SRA had a 47.4% mortality, compared to 51.4% in those given no more heparin (p = 0.63). Table 1 summarizes these findings. CONCLUSIONS: This is the largest study to date looking at patients with indeterminate SRA testing results, in which platelets exhibit high levels of serotonin release at both low and high heparin concentrations. Our data suggest 1) the majority of patients with indeterminate SRAs likely did not have HIT, 2) as evidenced by the low 4T scores and heparin-PF4 antibody levels, an indeterminate SRA suggests thrombocytopenia related to in-vivo platelet activation, and 3) an indeterminate SRA is associated with increased mortality. SRA results warrant a case-by-case assessment of the clinical picture in order to avoid unnecessary cessation of heparin products. Further studies exploring the mechanism leading to high serotonin release at both low and high heparin concentrations, causing an "indeterminate" SRA result, are warranted. Disclosures No relevant conflicts of interest to declare.

Spontaneous Tumoural Regression in a Patient with t(4;14) Translocation Multiple Myeloma. A Case Report.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4777-4777
Author(s):  
Noemi Puig ◽  
Christine Chen ◽  
Joseph Mikhael ◽  
Donna Reece ◽  
Suzanne Trudel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Case Report ◽  
Bone Marrow Biopsy ◽  
Peripheral Blood ◽  
Low Dose ◽  
Plasma Cells ◽  
Protein Electrophoresis ◽  
Urine Collection ◽  
Normal Limits

Abstract INTRODUCTION Despite recent advances, multiple myeloma continues to be an incurable malignancy, with a median overall survival (OS) of 29–62 months. A shortened survival is seen in myeloma patients having a t(4;14) translocation either with standard or high-dose chemotherapy (median OS 26 and 33 months, respectively). CASE REPORT A 60 year-old female was found to have a high ESR (121mm/h) and low hemoglobin (113g/L) in December 2005. Further work-up led to the diagnosis of stage 1A (Durie-Salmon) multiple myeloma on the basis of the following investigations: a protein electrophoresis showed IgG 12.2g/L, IgA 23.4g/L and IgM 0.33g/L with an IgA-kappa paraprotein; a bone marrow biopsy revealed 20–30% infiltration with atypical plasma cells, kappa restricted; IGH-MMSET fusion transcripts were detected by RT-PCR, consistent with the presence of t(4;14) positive cells in the specimen; a metastatic survey showed generalized osteopenia throughout the axial skeleton and multiple subtle permeative lucencies in the proximal humeral diaphyses bilaterally. A 24-hour urine collection showed 0.05g/L proteinuria with no Bence-Jones proteins detected. Her peripheral blood counts were as follows: hemoglobin 118g/L (MCV 91fL), platelets 275 bil/L and white blood cells 6.6 bil/L with 3.9 neutrophils and 1.8 lymphocytes. Her electrolytes and calcium were within normal limits but she had a slightly elevated creatinine at 107umol/L (normal <99). Her b2-microglobulin, C-reactive protein and albumin were all normal at 219nmol/L (normal ≤219), 4mg/L (normal ≤12) and 36g/L (36–50) respectively. No active therapy was recommended apart from monthly PAMIDRONATE for permeative lucencies. Her past medical history was significant for an IgA cryoglobulinemia diagnosed in 1985 when she presented with arthritis, purpura and Raynaud’s phenomenon. Her cryocrit has been ranging from 0–25% over the years; most recently still at 5%. She did not require any treatment until 1989 when she was started on low dose-steroids. Her flares consist mainly of lower limbs arthritis and purpura and they have been treated with intermittent PREDNISONE 5–7.5mg per day. A progressive drop in her M-protein has been documented since June 2006 with her most recent protein electrophoresis revealing no paraprotein, quantitative IgG is 7.7g/L, IgA 2.23g/L and IgM 0.63g/L. A bone marrow biopsy has shown less than 5% plasma cells. Her peripheral blood counts and biochemistry remained within normal limits and her skeletal survey is unchanged. A 24-hour urine collection shows no significant proteinuria (0.07g/L). Her free light chains assay revealed kappa 13.8mg/L and lambda 11.0mg/L with a ratio kappa/lambda 1.3. CONCLUSIONS We have documented tumoural regression in a patient with IgA-kappa multiple myeloma and t(4;14) only receiving intermittent low dose PREDNISONE and monthly PAMIDRONATE. This exceptional phenomenon has been well described with other malignancies such as testicular germ cell tumours, hepatocellular carcinomas and neuroblastomas; however, to the best of our knowledge, only in 2 cases of multiple myeloma. The unusual nature of this finding is highlighted by the presence of the t(4;14) in the plasma cells, known to be associated with more aggressive disease. The underlying mechanisms, speculated to be immunological for most of the other cancers, remain completely unknown in this case.

Allogeneic Hematopoietic Cell Transplantation (allo-HCT) Can Induce Durable Remission in Heavily Pretreated Relapsed Hodgkin Lymphoma. (HL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1192-1192
Author(s):  
Robert Chen ◽  
Joycelynne Palmer ◽  
Leslie Popplewell ◽  
Jessica Shen ◽  
Eileen Smith ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Unrelated Donor ◽  
Heavily Pretreated

Abstract Abstract 1192 Poster Board I-214 Background: Even though Hodgkin lymphoma (HL) is a curable disease, about, 20-30% patients are either refractory to induction chemotherapy or relapse post treatment. High dose chemotherapy and autologous HCT has been shown to be an effective salvage therapy for patients with relapsed HL. However, relapse continues to occur after auto-HCT, especially in patients with chemoresistant or poor-risk features at relapse. The prognosis of these patients is poor with limited options of treatment. Although allo-HCT offers both cytoreduction and potential graft-versus-tumor effect, its use in relapsed HL has been limited by non-relapse mortality (NRM) and patient co-morbidities induced by numerous prior treatments. To examine the potential impact of allo-HCT on survival and disease outcomes, we performed retrospective analysis of allo-HCT in relapsed/refractory HL to determine if allo-HCT can induce long-term remission in heavily pretreated relapsed HL. Results: Between January 2003 and December 2008, 29 patients with relapsed HL underwent allo-HCT at City of Hope National Medical Center. The median age was 37 (range: 14-63). 20 (69%) patients were chemosensitive at time of allo-HCT. 17 (59%) patients had prior auto-HCT. 16 (55%) patients received matched siblings and 13 (45%) received unrelated donor cells. 20 (69%) patients had prior radiation treatments. The median number of prior regimens was 5 (range: 2-8). 23 (79%) patients underwent a non-myeloablative conditioning regimen while 6 (21%) patients had a myeloablative regimen. 14 (48%) patients received Tacrolimus/Sirolimus as graft versus host disease prophylaxis and 15 (52%) patients received a combination of Cellcept/CsA, Cellcept/CsA/MTX, Tacrolimus/MTX, or Tacrolimus/Sirolimus/MTX. With a median follow up of 31.9 months (range: 9.7-69.1) for surviving patients, the results show: Conclusion: Allogeneic hematopoietic cell transplantation in heavily pretreated relapsed Hodgkin's lymphoma is feasible, tolerable, and can induce durable clinical remissions. Disclosures: No relevant conflicts of interest to declare.

Treatment of Recurrent or Persistent AML/MDS After Allogeneic Hematopoietic Cell Transplantation with Azacitidine.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1288-1288
Author(s):  
Jennifer Vaughn ◽  
Barry Storer ◽  
Marco Mielcarek ◽  
Edus H. Warren ◽  
Paul J. Martin ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Induction Chemotherapy ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Case Series ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Persistent Disease ◽  
Relapsed Disease

Abstract Abstract 1288 Recurrence or persistence of disease after hematopoietic cell transplantation (HCT) remains a significant obstacle in the treatment of patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndromes (MDS). Standard therapies for relapsed disease include withdrawal of immunosuppression (WIS), donor lymphocyte infusion, induction chemotherapy, and in selected patients, a second HCT. Regardless of the intervention chosen, survival for post-transplant relapse has been dismal. Effective therapies without significant toxicity are needed. Azacitidine, a DNA demethylating agent, is the only non-HCT therapy shown to prolong survival in patients with MDS. It has also shown efficacy in patients with AML when used alone as induction or consolidation therapy or in combination with the anti CD-33 antibody gemtuzumab. Its use following HCT was inspired by the discovery of the drug's potential to enhance the graft-versus-leukemia effect through demethylation of the KIR regions on donor NK cells and by enhancing HLA-DR2 expression on leukemic blasts. It has also been shown to modulate T-cells post-engraftment and may result in lower rates of GVHD without impairing the GVL effect. Several small case series have been published evaluating azacitidine as therapy for treatment of relapse following HCT and have demonstrated improvement in disease status. None of these studies have examined azacitidine in the setting of persistent disease, which has become more relevant with the use of lower intensity conditioning regimens and the use of new methods to detect the presence of disease at extremely low levels. In this retrospective study, we determined the outcomes of patients treated with azacitidine (75 mg/m2/day for 7 days +/− gemtuzumab (3mg/m2) on day 9, every 4 weeks) for post-HCT recurrence or persistence of AML/MDS. Azacitidine treatment was initiated following HCT if there was evidence of recurrent or persistent disease (defined as any recurrent abnormal blasts detected by flow on peripheral blood or marrow or recurrent cytogenetic abnormalities). Seventeen (74%) of the patients had AML while 6 (26%) had MDS. FAB subtypes of the latter included RAEB (3), RA (1), CMML (1) and unclassified (1). Eighteen (78%) patients underwent conventional high dose conditioning, and 5 (22%) patients underwent nonmyeloablative conditioning prior to HCT. Eleven (48%) of patients had low risk cytogenetics, 3 (13%) had intermediate risk, and 9 (39%) had high risk cytogenetics. Seventeen (74%), 0 (0%) and 6 (26%) of patients were diagnosed with persistent or relapsed disease within 100, 100–200 and > 200 days following HCT. Patients began azacitidine 0–242 (median: 17) days from time of relapse and completed a median of 2 azacitidine cycles (range 1–8). Overall 6-month survival from the day of relapse was 57% and from start of azacitidine therapy was 48%. Among the 18 patients who started azacitidine within 2 months of documented relapse the 6-month survival was 50%. Blast count at time of relapse was not significantly associated with survival (> 1% vs ≤ 1%, HR=1.26, p=0.63), nor was survival after initial treatment with azacitidine affected by longer time intervals prior to first administration (> 28 days vs ≤ 28 days, HR=0.85, p=0.76). There were 12 patients who received gemtuzumab with azacitidine, and the addition of gemtuzumab made no difference in survival (HR with gemtuzumab = 0.81 (0.3-2.1), p=0.66). The 6-month survival with azacitidine is superior to that observed with induction chemotherapy (20%) or WIS (10%). Azacitidine therapy may be superior to standard therapies for recurrent/persistent disease following HCT and warrants further study. Disclosures: No relevant conflicts of interest to declare.

A Case of Hemophagocytic Lymphohistiocytosis with Acute Myelofibrosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5070-5070
Author(s):  
Nanda K. Methuku ◽  
Nidhi Mishra ◽  
Gloria Fernandez ◽  
Praveena Coimbatore ◽  
Sammy Selahi
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Physical Examination ◽  
Peripheral Blood ◽  
Hemophagocytic Lymphohistiocytosis ◽  
High Dose ◽  
Intermittent Fever ◽  
Runny Nose ◽  
Serological Studies ◽  
Wbc Count

Abstract Abstract 5070 Title: A case of Hemophagocytic Lymphohistiocytosis with Acute Myelofibrosis Case report: A 60 year old previously healthy male was admitted for a four week history of non-productive cough, and intermittent fever which was getting worse since 1 week prior to presentation. He also had runny nose and nasal stuffiness 2 months prior to presentation. The patient also had significant weight loss of 30 lbs over the past month. Physical examination was remarkable for a temperature of 38°C. Patient was alert and oriented. No Lymphadenopathy or hepatosplenomegaly was found. Rest of the physical examination was otherwise unremarkable. Laboratory findings on admission: hemoglobin 10.1 g/dl, white blood cell count 1000 /ml (with 58.5% neutrophils, 36.9% lymphocytes 3.4% monocytes), platelet count 111,000 /ml, reticulocyte count 1.3 % and an erythrocyte sedimentation rate 4 mm, total bilirubin 0.8 mg/dL (with 0.4 mg/dL conjugated), alkaline phosphatase 62 U/L, AST 113 U/L, ALT 137 U/L, triglyceride 388 mg/dL, LDH 513 IU/L, ferritin was > 2000 ng/mL, PT 12.2 sec PTT 26.8 sec and fibrinogen 154 mg/dl No pathogens were isolated from throat, urine, feces, or blood. H1N1 testing; serological studies for hepatitis A, B, D, and E; Quantiferon test for tuberculosis; Serological studies for Human immunodeficiency virus (HIV), Cytomegalovirus (CMV), Epstein-Bar virus (EBV), parvovirus; antinuclear antibody, rheumatoid factor, lupus anticoagulant were all negative. Peripheral blood examination revealed normochromic-normocytic anemia. There was no evidence of micro-angiopathy or other marrow infiltration. A bone marrow biopsy was performed which showed a hypercellular marrow, with absence of myeloid precursors and decrease in erythroid cells. The predominant components were atypical megakaryocytes, plasma cells and eosinophils Reticulin stain showed marked increase in coarse reticulin. Occasional large histiocytes were visualized with engulfed lymphocytes, polymorphonuclear and red blood cells. Flow cytometry was negative for a myeloproliferative disorder. The platelet and WBC count nadirs were 73,000/mL and 800/mL (53% polymorphonuclear cells) at days 5–7 of admission. He continued to have cytopenias with intermittent febrile episodes despite being on broad spectrum antibiotics and antifungals. Based on pancytopenia, intermittent fever, elevated liver enzymes, very high ferritin level, high triglyceride level and evidence of hemophagocytosis on bone marrow exam a diagnosis of Hemophagocytic Lymphohistiocytosis was made. Patient received IV Ig for 2 days along with high dose steroids with prophylaxis with IV proton pump inhibitors, after which his fever resolved. LDH decreased from a peak of 900 to 300 and his leucopenia resolved with a WBC count of 3,000 /ml 5 days after 1st dose of IV Ig. Patient seemed to be responding very well to the treatment, but he had an episode of massive GI bleed on the fifteenth day of hospitalization with malena and he could not be resuscitated. No autopsy was performed. Discussion: We describe a case of possible secondary Hemophagocytic Lymphohistiocytosis (HLH) with Acute Myelofibrosis. A diagnosis of HLH was made based on the proposed diagnostic criteria, 2009 by Dr. Filipovich. Acute Myelofibrosis was evidenced by marked increase in reticulin stain with absence of splenomegaly or tear drop cells on peripheral blood smear. Viral infection could have been a trigger for HLH in this patient as he had runny nose 2 months before presentation. The patient responded very well to IVIg and high dose steroids as evidenced by an increase in WBC and platelet count, resolution of fever and decrease in LDH. HLH is a rare and potentially fatal condition with excessive activation of macrophages and T cells with an overwhelming systemic inflammatory reaction. Viruses are implicated as the most common triggers for secondary HLH. Our case adds to the literature on the rare disease and will help in understanding the disease better. Disclosures: No relevant conflicts of interest to declare.

First Case of Platelet-Type Von Willebrand Disease (PT-VWD) Associated with Type 2B Von Willebrand Disease (2B VWD)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5313-5313
Author(s):  
Marie Dreyfus ◽  
Celine Desconclois ◽  
Corinne Guitton ◽  
Marie-Jeanne Baas ◽  
Helene Mandard ◽  
...  
Keyword(s):  
Platelet Count ◽  
Von Willebrand Disease ◽  
Biological Study ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
First Case ◽  
Platelet Receptor ◽  
Biological Phenotype ◽  
Neonatal Thrombocytopenia ◽  
Von Willebrand

Abstract Abstract 5313 Introduction VWD 2B and PT-VWD are rare diseases, due to mutations inducing a gain of function respectively of von Willebrand factor (VWF) and of its platelet receptor, Glycoprotein (GP)1bα Case history We report here the case of a young girl, born with an extensive purpura and a severe thrombocytopenia: platelet count: 16G/L. There was no associated biological nor clinical abnormality. A high dose of 1g/kg of immunoglobulin G infused on day 1 was unsuccessful, and a HPA-1a (−) platelet concentrate infusion led to a partial and transient increase of the platelet count up to 60G/L. Thrombocytopenia then resolved spontaneously. Biological study showed no sign of materno-fetal allo- or auto-immunity, parents were not consanguineous. The diagnosis of type 2B VWD was performed when she was 5 months old: VWF:RCo < 13 IU/dl, VWF:Ag 60 IU/dl, positive ristocetin induced platelet aggregation (RIPA) at a low ristocetin concentration (0.5 mg/ml). RIPA mixing studies were unconclusive. The same biological abnormalities were found in the father, whereas the mother had normal hemostasis tests. The biological phenotype also included a study of the multimeric VWF structure, showing a marked decrease in percentage of VWF high and intermediate molecular multimers. Genetic analysis performed on VWF gene showed the heterozygous p.Pro1266Leu missense mutation in the VWF A1 domain. This mutation ( o ) is only slightly deleterious, and induces usually a mild disease, without thrombocytopenia, even in stress situations, with normal VWF multimeric distribution; therefore, it could not explain the biological phenotype severity in this family. GPIBA was then analysed, and a candidate point mutation p.Met239Ile was evidenced. This mutation had not been described yet, but p.Met255Val had already been found in diagnosed cases of PT-VWD. Conclusion This case underlines the utmost importance to characterize precisely neonatal thrombocytopenia mechanism. Furthermore, it points out the difficulties to performing PT-VWD diagnosis, which incidence is most probably underestimated. In our case, it was the systematic and extensive biological workout performed in this case of isolated neonatal thrombocytopenia, without any obvious cause, which led to the diagnosis of a PT-VWD, inducing a severe biological phenotype, associated with type 2B VWD characterized by a mild expression. It is, to our knowledge, the first case described to date of such a morbid association. Disclosures: No relevant conflicts of interest to declare.

Recommended Tools for Joint Chronic Graft-Versus-Host Disease: Results From the Chronic Gvhd Consortium

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 464-464
Author(s):  
Yoshihiro Inamoto ◽  
Xiaoyu Chai ◽  
Brenda Kurland ◽  
Daniel J. Weisdorf ◽  
Paul J. Martin ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Symptom Burden ◽  
Assessment Tools ◽  
The Other ◽  
Joint Involvement ◽  
High Dose ◽  
Symptom Scale ◽  
Multicenter Observational Study

Abstract Abstract 464 Background: Assessing joint chronic GVHD needs to be accomplished reliably, simply and in a clinically meaningful way. To determine the optimal tool for assessing joint GVHD, we evaluated 2 NIH recommended joint tools (Table), a photographic range of motion (P-ROM) scale, and 7 other NIH recommended tools (Lee symptom scale, 10-point overall symptoms, FACT-G, SF36, Human Activities Profile, walk test and grip test). Methods: Patients ≥ age 2 with systemically treated chronic GVHD ≤ 3 years after hematopoietic cell transplantation were eligible for a prospective multicenter observational study. Incident and prevalent cases were included. At follow-up visits every 3–6 months, the clinician (MD) and patient (PT) rated separately their perception of change in joint GVHD on an 8-pt scale, which was collapsed into improved, stable or worse categories. Linear mixed models were used to correlate change in each tool with MD or PT-perceived change (improved vs. stable or worse vs. stable) in joint GVHD status. Results: Nine sites in the Consortium enrolled 567 participants through December 2011. Joint involvement, as defined by NIH joint/fascia score ≥1, was present at enrollment in 164 (29%) patients and included wrists (64%), ankles (47%), shoulders (35%) and elbows (30%). Joint involvement at enrollment was associated with longer duration of chronic GVHD, high-dose total body irradiation, higher symptom burden, lower quality of life (QOL), similar activity profile and similar physical function, compared to those without joint involvement. Change in joint GVHD status was examined for 652 paired visits when joint involvement was documented in the previous or current visit. In the later visits, both MDs and PTs more often reported improvement (44% and 45%) than worsening (5% and 11%). Tools that correlated with both MD and PT-perceived joint improvement were NIH joint/fascia score, Hopkins fascia score and SF36-PCS. Tools that correlated with both MD and PT-perceived joint worsening were P-ROM total score, NIH joint/fascia score, Hopkins fascia score, Lee muscle/joint subscale, Lee symptom overall score, 10-point overall symptoms and FACT-G. Among the 3 joint/fascia tools (Figure), for MD-perceived improvement, estimated change in the NIH score and P-ROM score was slightly larger than in the Hopkins score. For PT-perceived improvement, estimated change was similar for NIH and Hopkins scores. In contrast, for both MD and PT-perceived worsening, estimated change for the P-ROM score was significantly larger than in the other tools. Conclusion: Joint involvement with chronic GVHD is frequent and associated with increased symptom burden and decreased QOL. Our results support the combined use of NIH joint/fascia score and P-ROM scale to assess joint GVHD. The NIH score better reflects joint improvement and the P-ROM scale better reflects joint worsening. The more objective P-ROM scale is insensitive to PT-perceived joint improvement possibly because unlike the other two joint assessment tools, it does not incorporate tightness with or without activities of daily living. Disclosures: No relevant conflicts of interest to declare.

Hepatosplenic T Cell Lymphoma Mimicking Hemophagocytic Lymphomhistiocytosis: A Case Report

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4864-4864
Author(s):  
Inhye E Ahn ◽  
Lawrence Rice
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cell Phenotype ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Gamma Delta ◽  
Bone Marrow Biopsies ◽  
Hepatosplenic T Cell Lymphoma

Abstract Abstract 4864 Background. Hepatosplenic T cell lymphoma (HSTCL) is rare and aggressive extranodal lymphoma characteristically involves young males in third or fourth decade of life. It frequently manifests as pancytopenia with severe thrombocytopenia, hepatosplenomegaly, and much rarely, hemophagocytic lymphohistiocytosis (HLH). Methods. Medical records of a patient who presented with HLH as a presenting signs of HSTCL were reviewed. Literature search was performed to identify characteristic demographics and natural course of HSTCL reported to date. Results. A 30-year-old male presented after 6 months of constitutional symptoms. Remarkable findings were pancytopenia, mildly elevated LFT, and high ferritin level (89,000). Extensive work up for autoimmune and infectious etiology was negative. Worsening anemia and thrombocytopenia prompted the third bone marrow biopsy, which revealed the first evidence of hemophagocytosis. Despite of Cyclosporine A and Etoposide, pancytopenia worsened which prompted splenectomy and core needle liver biopsy. Sinusoids of spleen and liver were densely infiltrated with atypical lymphocytes consistent with T cell phenotype. Diagnosis of HSTCL was confirmed after PCR detection of gamma delta T cell receptor rearrangement. Previous bone marrow biopsies were retrospectively reviewed, which revealed small clusters of cells staining positive for CD3. The patient underwent three courses of chemotherapy that included high-dose Cytarabine, Etoposide and adriamycin. Post-chemotherapy course was complicated with disseminated Candidiasis complicated with mycortic aneurysm and worsening pancytopenia. The patient expired due to overwhelming septic shock 6 months after the pathologic diagnoses of HSTCL. Conclusion. HSTCL causes aberrant expansion of gamma delta T cells and defective innate immunity, and is an important secondary etiology for HLH. Splenectomy has diagnostic significance but little therapeutic benefit. Longer survival was reported in patients who underwent cytarabine-based chemotherapy; however median survivals in anecdotal case series all fall within 2 years regardless of regimen. Disclosures: No relevant conflicts of interest to declare.

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