Clinical Heterogeneity Of Autoimmune Hemolytic Anemia: A 35-Years Retrospective Study Of 157 Patients

Abstract The clinical presentation of autoimmune hemolytic anemia (AIHA) is greatly heterogeneous, from mild/compensated to life-threatening forms. The aim of this study was to correlate the clinical and serological characteristics of the disease, usually classified as warm (WAIHA), cold (CHD), and mixed, based on the thermal and isotype characteristics of the anti-RBC antibody (IgG, IgM or both, respectively). One-hundred fifty seven AIHA patients (61 M and 96 F, median age 57, range 5-95) referred to our institution from 1978 to September 2012 were investigated. They had been followed-up for a median of 26 months (range 12-271), and 50% were still in follow-up. As regards the thermal characteristics 40% of cases were WAIHA, 32% CHD, 19% mixed forms and 9% atypical (12 DAT negative and 1 DAT positive for IgA only). Considering the severity of anemia at onset 33% of cases had Hb levels<6 g/dl, 34% Hb 6-8 g/dL, 18% Hb 8-10 g/dL, and 15% Hb>10 g/dL. The most severe AIHA cases were mainly mixed (18/30, 60% p=0.001) and atypical (6/13, 46%) forms, whereas only a small fraction of CHD was characterized by a severe onset (8/51, 16% p=0.002). Reticulocytopenia (<100.000 mmc) was more frequently observed in cases with severe onset (14/52, 27%), possibly contributing to the clinical picture. Eleven patients experienced an acute event at the onset of hemolysis and the majority of them (7/11, 63% ) were WAIHA; we recorded 4 deep venous thrombosis (with 2 subsequent pulmonary embolisms), 1 disseminated intravascular coagulation, 3 cardiac ischemic events, 2 acute renal failure and 4 acute infection (3 pneumonias and 1 sepsis); 18 patients died because of AIHA during the follow up. As regard therapy, we considered steroids, splenectomy, cytotoxic drugs and rituximab: 45% of cases (mostly WAIHA) were treated with steroids only, 23% with 2 lines, 10% with 3, and 6% with 4 or more lines; splenectomy was performed in 20 cases, mostly mixed and severe forms (p=0.001); 23 patients were treated with various cytotoxic drugs, and 33 with rituximab (the latter was more frequently administered in clinically severe cases, and in mixed and atypical forms, p=0.009). On the whole, the most severe patients were those who underwent 3 or more lines of therapy, compared with the other cases (14/52 versus 11/105, p=0.015). Finally, 16% of cases have never been treated, mostly CHD with mild anemia. Transfusions were performed in 65 cases, plasma-exchange in 3 (all with Hb<6 g/dL), and erythropoietin administered in 6 cases. Of note, the presence of an Hb value lower than 6 g/dL at onset was a risk factor for the requirement of 3 or more lines of therapy (odds ratio 3.148, CI 95% 1.312-7.552). Response rates to steroid therapy were similar in warm, cold, mixed and atypical AIHAs (on average 70%). Responses to rituximab were similar in cold and other AIHA forms (70-80%). Splenectomy, was ineffective in the 2 CHD who underwent surgery, whereas response rates were 63% in WAIHA and 80% in mixed and atypical cases. In conclusion, AIHAs showed a marked clinical heterogeneity, 1/3 of cases with a severe onset and with life threatening complications. These cases are frequently mixed or atypical forms and refractory to different therapies. Disclosures: No relevant conflicts of interest to declare.

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Safe Start of Ibrutinib in Patients with Chronic Lymphocytic Leukemia and Uncontrolled Autoimmune Hemolytic Anemia

Blood ◽

10.1182/blood-2018-99-120129 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5560-5560 ◽

Cited By ~ 1

Author(s):

Alejandro Garcia-Horton ◽

Rosanne St. Bernard ◽

Alejandro Lazo-Langner ◽

Anargyros Xenocostas ◽

Joy Mangel ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Conflicts Of Interest ◽

Case Reports ◽

Laboratory Data ◽

Case Series ◽

Lymphocytic Leukemia ◽

Positive Direct

Abstract It is estimated that 4-10% of patients with chronic lymphocytic leukemia (CLL) will develop autoimmune hemolytic anemia (AIHA) over the course of their disease. Ibrutinib has proven to be effective in treatment of relapsed, refractory, 17p deleted, and treatment naïve CLL. The effect of ibrutinib on AIHA in the context of CLL has not been established since patients with active hemolysis were excluded from major trials. In this abstract, we present a case series of patients that were actively hemolyzing at the start of ibrutinib therapy and in which their AIHA achieved prolonged response. Patient characteristics and laboratory data are shown in Table. Five patients (3 women, 2 men), median age 61 years (range 57 to 78), with CLL and active, uncontrolled AIHA at the time of ibrutinib initiation were identified. Uncontrolled AIHA was defined as anemia with evidence of hemolysis (at least two of the following: increased reticulocyte count, elevated lactate dehydrogenase, elevated indirect bilirubin, and reduced haptoglobin and a positive direct antiglobulin test (DAT)). Patients had a median hemoglobin of 70 g/L (range 69-96) prior to start of ibrutinib and 3 of them required transfusion support for symptomatic anemia. All patients were receiving prednisone for management of AIHA at the time of ibrutinib initiation and had been on it for a median of 10 days (range 9 - 25) without AIHA resolution. 1 patient received intravenous immunoglobulin concurrently. All patients had received at least one line of therapy for CLL in the past and 3 had experienced previous AIHA responsive to steroids. AIHA in 2 patients was related to previous fludarabine exposure but had responded to a prednisone tapering schedule and were off steroids by the time of the new AIHA flare. Median hemoglobin of 130 g/L (range 113-149) was reached at time of AIHA response. All 5 patients tolerated 420mg oral daily of ibrutinib therapy and AIHA was controlled in a median of 6.5 weeks (range 6-10). Discontinuation of steroids was achieved in all patients at a median of 10 weeks (range 6-17) without evidence of further hemolysis. All patients except one are receiving ongoing follow up and have been followed up for a median of 130 weeks (range 15-150) since ibrutinib start. Patients have not shown evidence of AIHA relapse and continue off AIHA treatment (prednisone). One patient required discontinuation of ibrutinib 6 months after starting due to neutropenia but there was no evidence of AIHA relapse in follow up. The patient has passed away from unrelated GI bleed 2 years after the initial AIHA event. This is the largest case series to our knowledge on the safe start of ibrutinib in CLL complicated by active AIHA. Hemolysis in all patients responded to a short prednisone taper with ibrutinib concurrently and obtained a sustained response at follow up without any flare ups or further AIHA treatment use. These cases suggest that it is safe to start ibrutinib during uncontrolled, active hemolysis in contrast to 2 previous case reports that suggested causal relationship between ibrutinib and onset of severe CLL-associated AIHA (Rider et al, 2015; Hodskins et al, 2014). As previously reported, AIHA occurrence or relapse once ibrutinib has been started is rare (Rogers et al, 2016). Disclosures No relevant conflicts of interest to declare.

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Efficacy and Safety of Monoclonal Anti-CD20 Antibody Rituximab Combined Cyclophosphamide in Treatment of Refractory and Recurrent Autoimmune Hemolytic Anemia

Blood ◽

10.1182/blood.v120.21.5161.5161 ◽

2012 ◽

Vol 120 (21) ◽

pp. 5161-5161

Author(s):

Zonghong Shao ◽

Hong Liu ◽

Limin Xing ◽

Yuhong Wu ◽

Wen Qu ◽

...

Keyword(s):

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Conflicts Of Interest ◽

Additional Treatment ◽

Efficacy And Safety ◽

Indirect Bilirubin ◽

Mean Response Time ◽

Cd20 Antibody ◽

Anti Cd20

Abstract Abstract 5161 Objectives: To better assess the efficacy and safety of monoclonal anti-CD20 antibody rituximab in the treatment of refractory and recurrent autoimmune hemolytic anemia. Patients and methods: 7 cases with autoimmune hemolytic anemia (including 1 case of Evans syndrome) were enrolled into this study, they were treated with rituximab (375 mg/m2, once per week, 2–6 times) and Cyclophosphamide(1g/10days, 2–6 times) combined with intravenous immunoglobulin (IVIG) (10g/week, given 1 day after rituximab treatment). Results: All 7 patients showed good responses. 6 achieved complete remission (CR) and 1 achieved partial remission (PR). Responses were seen at 1th to 10th month after the first dose of rituximab and the mean response time was approximately 2. 5 months. Average follow-up time for them isfor the patients was 27 months. All patients remained in remission at the 12-month follow-up. At the time of 24-month follow up, 3 patients showed elevated indirect bilirubin and increased reticulocyte counts. One of the 3 patients achieved CR after additional rituximab therapy, and the other 2 PR after additional cyclophosphamide therapy. At the time of 36-month follow up, 1 patient relapsed and was retreated with 3 cycles of rituximab and eventually reached PR. All patients tolerated the treatment well with only mild side effects. Conclusion: rituximab is highly effective and relatively safe in patients with refractory and recurrent autoimmune hemolytic anemia. Maybe Additional treatment can be given in patients with relapse after 1–2 years. Disclosures: No relevant conflicts of interest to declare.

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Autoimmune Hemolytic Anemia as a Complication of Congenital Anemias. A Case Series and Review of the Literature

Journal of Clinical Medicine ◽

10.3390/jcm10153439 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3439

Author(s):

Irene Motta ◽

Juri Giannotta ◽

Marta Ferraresi ◽

Kordelia Barbullushi ◽

Nicoletta Revelli ◽

...

Keyword(s):

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Case Series ◽

Intravenous Immunoglobulins ◽

Point Of View ◽

First Line ◽

Human Erythropoietin ◽

Immune Mediated ◽

Hemolytic Crisis ◽

Life Threatening

Congenital anemias may be complicated by immune-mediated hemolytic crisis. Alloantibodies are usually seen in chronically transfused patients, and autoantibodies have also been described, although they are rarely associated with overt autoimmune hemolytic anemia (AIHA), a serious and potentially life-threatening complication. Given the lack of data on the AIHA diagnosis and management in congenital anemias, we retrospectively evaluated all clinically relevant AIHA cases occurring at a referral center for AIHA, hemoglobinopathies, and chronic hemolytic anemias, focusing on clinical management and outcome. In our cohort, AIHA had a prevalence of 1% (14/1410 patients). The majority were warm AIHA. Possible triggers were recent transfusion, infection, pregnancy, and surgery. All the patients received steroid therapy as the first line, and about 25% required further treatment, including rituximab, azathioprine, intravenous immunoglobulins, and cyclophosphamide. Transfusion support was required in 57% of the patients with non-transfusion-dependent anemia, and recombinant human erythropoietin was safely administered in one third of the patients. AIHA in congenital anemias may be challenging both from a diagnostic and a therapeutic point of view. A proper evaluation of hemolytic markers, bone marrow compensation, and assessment of the direct antiglobulin test is mandatory.

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NUDT15 polymorphism explains serious toxicity to azathioprine in Indian patients with chronic immune thrombocytopenia and autoimmune hemolytic anemia: a case series

Drug Metabolism and Personalized Therapy ◽

10.1515/dmpt-2020-0128 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Anup J. Devasia ◽

Raveen Stephen Stallon Illangeswaran ◽

Infencia Xavier Raj ◽

Biju George ◽

Poonkuzhali Balasubramanian

Keyword(s):

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Immune Thrombocytopenia ◽

Case Series ◽

Severe Toxicity ◽

Toxic Side Effect ◽

Case Presentation ◽

Oral Ulcers ◽

Asian Patients ◽

Life Threatening

AbstractObjectivesAzathioprine (AZA) is a commonly used immunosuppressant in patients with autoimmune diseases. The toxic side effect to AZA (myelosuppression, hair loss, and oral ulcers) are highly unpredictable which can be life threatening if not identified earlier and dose adjustments made or the drug is withdrawn.Case presentationHere we report a case series of five patients with severe toxicity while on treatment with AZA for autoimmune hemolytic anemia (n=1) and Immune thrombocytopenia (n=4). The common thiopurine methyltransferase (TPMT) variants (TPMT*2, *3A, *3B) were not present in these patients. However, all these patients had the NUDT15 415C>T variant that has been reported to explain serious toxicity to thioguanine in Asian patients.ConclusionsOur report suggests pre-emptive genotype-based dosing of AZA could reduce adverse toxicity and hence better outcome.

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A Retrospective Study of the Combination of Rituximab, Cyclophosphamide and Dexamethasone for the Treatment of Relapsed/Refractory Warm Antibody Autoimmune Hemolytic Anemia

Acta Haematologica ◽

10.1159/000501538 ◽

2019 ◽

Vol 143 (3) ◽

pp. 244-249 ◽

Cited By ~ 1

Author(s):

Caroline I. Piatek ◽

Hillel Bocian ◽

Sandra Algaze ◽

Ilene C. Weitz ◽

Casey O'Connell ◽

...

Keyword(s):

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Immune Modulation ◽

Complete Response ◽

Primary Objective ◽

Additional Treatment ◽

Lymphocytic Leukemia ◽

Immunocompromised Patients ◽

Treatment Changes

The combination of rituximab, cyclophosphamide, and dexamethasone (RCD) is highly effective in the treatment of warm autoimmune hemolytic anemia (WAIHA) associated with chronic lymphocytic leukemia (CLL). We treated a cohort of patients with relapsed/refractory WAIHA, without CLL, with RCD. The primary objective was to evaluate the overall response (OR) of RCD therapy. Complete response (CR) was defined as a hemoglobin (Hgb) ≥12 g/dL. Partial response (PR) was defined as Hgb 10–11.9 g/dL or ≥2 g/dL increase in Hgb. Sustained response was defined as Hgb ≥10 g/dL with no treatment changes. A total of 16 patients with relapsed/refractory WAIHA received RCD (7 primary WAIHA, 9 secondary WAIHA) for a median of 4 cycles (range: 2–6). The median pretreatment Hgb was 10.0 g/dL (range: 4.3–12.2). The median best Hgb achieved was 12.5 g/dL (range: 10.6–15.1) with a median of 2 cycles until best Hgb response. The OR was 94% (11 CR, 4 PR). Two immunocompromised patients were admitted for infections during RCD treatment. There were no deaths during the treatment or follow-up period. Following a response to RCD, 4 patients received noncorticosteroid immune modulation therapy and 4 patients continued on corticosteroid therapy. Seven patients received no additional treatment.

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A Rare Cause of Anemia in Inflammatory Bowel Diseases: A Case Report and Review of Literature

Blood ◽

10.1182/blood.v112.11.5385.5385 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5385-5385

Author(s):

Waqas Ahmed ◽

Kevin Monroe ◽

James Essell ◽

E. Randolph Broun

Keyword(s):

Case Report ◽

Hemolytic Anemia ◽

Inflammatory Bowel Diseases ◽

Autoimmune Hemolytic Anemia ◽

Blood Smear ◽

Rare Complication ◽

Peripheral Blood Smear ◽

Bowel Diseases ◽

Inflammatory Bowel

Abstract Introduction: Anemia is a common problem in patients with inflammatory bowel diseases (IBD), and its etiology is usually multifactorial. It can be produced by chronic blood loss, nutritional deficiencies, and drugs such as salazopyrine; however it can also due to auto immune hemolysis, which is a rare complication of IBD. We report a case of coombs positive autoimmune hemolytic anemia associated with ulcerative colitis both diagnosed at the same presentation. Case Report: A 32 year old man with no significant past medical history presented with complaint of dark colored urine, jaundiced skin and fatigue for 4 weeks. He also reported diarrhea mixed intermittently with blood for last few months. Physical exam was consistent with jaundice and anemia (pallor and icterus) with slightly palpable spleen. Initial lab work up showed Hb of 3.8 with normal platelet and WBC count, high reticulocytes count of 7% .LFT showed serum bilirubin of 3.6 (direct 0.4) with normal serum ALT and AST levels .Serum LDH was high (1032 U/l) while serum haptoglobin was low (0.11 mg/dl). Peripheral smear showed anisopoikilocytosis & spherocytosis. (See Figure 1) Further investigations revealed a positive direct Coombs test consistent with diagnosis of autoimmune hemolytic anemia. CT abdomen and pelvis showed mild splenomegaly & non-specific enlarged mesenteric lymph nodes. Colonoscopy revealed ulcerative pancolitis confirmed by histological findings of biopsies taken. Patient received PRBC transfusions and was started on steroids and mesalamine and was discharged on maintenance dose. His symptoms resolved in 4 weeks and Hb remained stable with no evidence of further hemolysis at 4 month follow up .Repeated CT abdomen & pelvis showed resolution of the lymphadenopathy. Figure 1: Peripheral Blood smear showing anisopoikilocytosis & spherocytosis. Figure 1:. Peripheral Blood smear showing anisopoikilocytosis & spherocytosis. Discussion: Autoimmune hemolytic anemia (AIHA) is a rare complication of IBD. The exact underlying pathogenesis of this association remains obscure; however it has been attributed to the production of cross reacting anti erythrocyte antibodies. In AIHA associated with IBD, corticosteroids are considered to be first line therapy and often cause remission of hemolysis along with treatment for IBD Immunomodulators and splenectomy has been used for patients with refractory AIHA. Colectomy done for fulminant colitis has also been reported to induce remission of AIHA. Further studies for long term follow up and pathogenesis of this association are warranted.

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The Addition of Thalidomide to the Induction Treatment of Newly Presenting Myeloma Patients Increases the CR Rate Which Is Likely to Translate Into Improved PFS and OS.

Blood ◽

10.1182/blood.v114.22.352.352 ◽

2009 ◽

Vol 114 (22) ◽

pp. 352-352 ◽

Cited By ~ 8

Author(s):

Gareth J Morgan ◽

Faith E Davies ◽

Walter M Gregory ◽

Susan E Bell ◽

Alex J Szubert ◽

...

Keyword(s):

Flow Cytometry ◽

Conflicts Of Interest ◽

Residual Disease ◽

Response Rates ◽

Multiparameter Flow Cytometry ◽

Induction Treatment ◽

Overall Response ◽

Patient Pathways ◽

The Impact

Abstract Abstract 352 We present updated results from MRC Myeloma IX study evaluating the role of the addition of thalidomide to the induction and maintenance of patients with myeloma. The study ran from May 2003 – November 2007 and randomised 1,970 patients and now has a median follow up of more than 3.5 years giving it improved power to detect changes in outcome developing later after treatment. Projected median OS younger fitter patients 66 months, median OS older less fit patients 32 months. The trial comprised of 2 patient pathways, one for younger fitter patients comparing CTD (cyclophosphamide, thalidomide, dexamethasone) with CVAD (cyclophosphamide, vincristine, adriamycin, dexamethasone), all patients going on to receive an ASCT – median age 59 years. In older less fit patients, melphalan and prednisolone (MP) was compared to CTD attenuated – median age 73 years. In both pathways following initial treatment, eligible patients were randomised to low-dose thalidomide or no maintenance. Patient's response was monitored using electrophoresis, serum free light chain and multiparameter flow cytometry. Cytogenetics was availabel on up to 60% of cases and gene expression on a subset of these. CTD is a well tolerated regimen with a good safety profile giving excellent survivals in both groups of patients despite a small increase in risk of VTE. Using modified EBMT criteria, the addition of thalidomide to induction treatment increases both response rates and depth of response for all age groups. Preliminary results as follows: overall response: CTD vs CVAD: 91% v 82%; CR 21% v 14% and 100 days post-HDM, better responses were seen in CTD with CR rates 65% v 48%. Remission depth was also greater in CTD with more patients achieving minimal residual disease negativity by flow cytometry. The addition of thalidomide increases response rates overall, and particularly complete response (CR) rates (a 17% increase in CR rates post HDM, p=.006). In older/less fit patients CTDa vs MP: overall response 83% v 46%; CR 21% v 4%. Definitive results of these analyses will be presented as well as how they translate into PFS and OS and by cytogenetic subgroup. There is a substantial increase in response with the inclusion of thalidomide but at a median follow-up of three years we are not as yet seeing a substantial increase in survival in either of the two broad patient groups. We have collected data on treatment at relapse to explore how this confounds OS data. Importantly modelling analyses indicate when and to what extent, with further follow-up, the survival differences that should accrue from this increase in CR rate are likely to translate into a survival benefit. These results have a number of important implications. We show the benefit of the addition of thalidomide to myeloma treatment but also highlight the importance of later analysis of such trials because of the emergence of significant changes at these later time points. We will present full updated results from the study including the impact of thalidomide on cytogenetic subgroups and in the maintenance setting. Disclosures: No relevant conflicts of interest to declare.

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The First Reported Case of Prenatal Diagnosis for Pyruvate Kinase Deficiency in a Chinese Family

Blood ◽

10.1182/blood.v118.21.5276.5276 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5276-5276

Author(s):

Jason CC So ◽

Mary Tang ◽

Rever Li ◽

Shau Yin Ha ◽

Serge Pissard ◽

...

Keyword(s):

Differential Diagnosis ◽

Prenatal Diagnosis ◽

Ethnic Groups ◽

Pyruvate Kinase ◽

Hemolytic Anemia ◽

Pediatric Patients ◽

Conflicts Of Interest ◽

Chinese Family ◽

First Case

Abstract Abstract 5276 Pyruvate kinase (PK) deficiency of red cells (EC: 2.7.1.40) is the commonest inherited enzyme deficiency in the glycolytic pathway, leading to chronic non-spherocytic hemolytic anemia (CNSHA). There are over 220 characterized mutations deposited in a public database (PKLR Mutation Database http://www.pklrmutationdatabase.com). Heterozygous carriers are asymptomatic but homozygotes or compound heterozygotes can have significant anemia leading to transfusion dependency, neonatal death and hydrops fetalis. All ethnic groups are affected but data on Chinese are very scanty. We describe the first case of prenatal diagnosis for PK deficiency in Chinese and emphasize that this disease is an important differential diagnosis in pediatric patients with hemolytic anemia. A Han Chinese presented with hepatosplenomegaly, severe anemia and unconjugated hyperbilirubinemia at birth, necessitating exchange transfusion on day 1 and prolonged phototherapy till day 10 of life. Glucose-6-phosphate dehydrogenase level was normal. His parents were unrelated and asymptomatic. Family history was unremarkable. He developed severe CNSHA on follow up, requiring monthly red cell transfusion to relieve symptoms and to maintain satisfactory growth. Iron chelation therapy was started at 2 years of age and splenectomy was performed at 4 years to reduce transfusion requirement. The baseline PK enzyme level was not known but both parents had a mildly reduced PK level. Genetic analysis of PKLR gene was performed. All 11 exons and promoter were screened using polymerase chain reaction (PCR)-denaturing high performance liquid chromatography followed by PCR-sequencing. The father was found to carry a mutation in exon 8: PKLR: c.1073 G>A (p.Gly358Glu) while the sequencing result was normal in the mother. Quantitative multiplex PCR of short fluorescent fragments detected a rare large deletion removing exon 4 to exon 10 of the PKLR gene in the mother. Gap-PCR mapping confirmed that it to be a deletion previously found in a Vietnamese family (Costa C et al Haematologica 2005) and an Australian family (Fermo E et al Br J Haematol 2005). Both mutations have not been previously reported in Chinese. The proband was found to carry the paternal point mutation and the maternal deletion. Because of the severe clinical course of their first child, the couple requested prenatal biopsy was performed at 12 week of gestation. The fetus was found to be simple heterozygous for the paternal mutation. Pregnancy was allowed to continue and a healthy baby was born. A PK assay performed at the age of 9 months was normal. Mutation studies in a peripheral blood sample at 10 months of age confirmed the PKLR genotype. There was no evidence of hemolytic anemia after 3 years of follow up. Because of its perceived rarity and benignity in many ethnic groups, PK deficiency does not enter early into the differential diagnosis of anemia in pediatric patients. Its potential to cause severe disease is often overlooked and delay in diagnosis is common (Pissard S et al J Pediatr 2007). Genetic characterization and genotype-phenotype correlation studies on PKLR in different populations are indicated to better characterize the disease spectrum and to define the role of prenatal diagnosis in PK deficiency. Disclosures: No relevant conflicts of interest to declare.

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Vasculitis Associated with Large Granular Lymphocytes Leukemia

Blood ◽

10.1182/blood.v120.21.5109.5109 ◽

2012 ◽

Vol 120 (21) ◽

pp. 5109-5109

Author(s):

Alexandra Audemard ◽

Thierry Lamy ◽

Benoit Bareau ◽

Felipe Suarez ◽

Margaret Macro ◽

...

Keyword(s):

Nk Cell ◽

Conflicts Of Interest ◽

Remission Rate ◽

Acute Infection ◽

Response To Therapy ◽

Laboratory Findings ◽

Peripheral Neuritis ◽

The Mean ◽

Lgl Leukemia

Abstract Abstract 5109 Background: Large granular leukemia (LGL) leukemia is derived from either T-cell or NK-cell lineages. Clinical presentation of LGL leukemia is dominated by recurrent infections associated with neutropenia, anemia, splenomegaly and auto-immune diseases. The association of vasculitis and LGL leukemia has been rarely reported and investigated. Objective: To improve knowledge about this association, we retrospectively describe the clinical and biological characteristics of patients, their response to therapy and their prognosis. Methods: We performed a retrospective study based on 229 patients included in the French national LGL proliferation registry and a national mailing survey to 1350 internists in order to collect medical characteristics of patients displaying both vasculitis and LGL leukemia. We retrospectively collected medical charts from 11 patients between September 1999 and February 2012. Medical history, hematologic laboratory tests and response to therapy were compiled at first presentation of LGL leukemia associated vasculitis (LAV) and at each visit. Results: At the time of diagnosis of LGL leukemia the mean age was 60. 3 years (range, 28–74 years). They were 9 women and two men. The mean of follow up was 45 months (range, 1–108). The main LGL lineage was T-LGL (10 patients, 91%) and only one NK-LGL was identified. Hematological laboratory findings revealed that 5 patients (45%) patients presented hyperlymphocytosis. The mean absolute circulating LGL count for the series was 1. 10 9/L (range, 0. 45–4. 59 x. 10 9/L). Three patient (27%) had neutropenia (<1. 5 x. 109/L), no one had thrombocytopenia. Anemia was detected in 4 patients (36%). The most frequently observed vasculitis was cryoglobulinemia (n=5). Three patients presented cutaneous vasculitis. Two patients had ANCA negative microscopic polyangiitis and one patient presented giant cell arteritis. Clinical features were dominated by skin localization e. g. purpura (91%), arthralgia (37%), peripheral neuritis (27%) and renal glomerulonephritis (18%). Leucocytoclastic vasculitis was histologically demonstrated in 6 cases. Ten vasculitis were treated: the most delivered treatment was the association of cyclophosphamide-corticosteroid (n=3), followed to methotrexate–corticoisteroid (n=2), chlorambucil-corticosteroid (n=2) and corticosteroid alone (n=2). One patient received azathioprine and corticosteroid. The complete remission rate was high 80% and a minority of them presented vasculitis relapse (27%). Three patients (27%) died: one related to LGL leukemia (acute infection) and the 2 others related to heart failure due to vasculitis. Conclusion: Association of LGL leukemia and vasculitis is rare but not fortuitous. Based on this retrospective analysis, it seems that LAV preferentially affect female patients, with a low LGL count. LAV present with frequent cutaneous involvement and have a good response to therapy. Pathophysiological link between LGL leukemia and vasculitis remains to be investigated. Disclosures: No relevant conflicts of interest to declare.

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