Evaluation the Risk Factor of Transplantation-Associated Thrombotic Microangiopathy.

Abstract Abstract 4527 Background: Transplantation-associated thrombotic microangiopathy (TA-TMA) is lifethrewten though rare complication of allogeneic hematopoietic stem cell transplantation (HSCT). Diagnosis of TA-TMA is difficult due to its variation of criteria. Recently two new diagnositic criteria for TA-TMA have recently been proposed: the Bone Marrow Transplant Clinical Trials Network (BMTCTN) and the International Working Group (IWG) criteria. Our purpose is to investigate the indence and risk facter of TA-TMA in our institute. Study design and methods: All 8 cases of TA-TMA previously diagnosed at our institution between October 2005 and August 2010 were retrospectively evaluated and analysised. Table I showed the transplant details and patients characteristics. Results: Six patients performed Matched Unrelated Donor HSCT, two were haploidentical donor HSCT. Four patients complicated with hypohepatia, but only three patients had renal insufficient. The incidence of central nervous symptom abnormalities or dysfunction was very high (sever of eight patients). Four of eight patients were CSA linked TA-TMA, withdrawing CSA resulted in complete response. The other four patients were no CSA linked TA-TMA and developed aGVHD or CMV infection before TA-TMA. They had badly response to common treatment including plasma exchange (PE), steroid treatment and immunosuppression decreased. All of them died of multiple organ failure. Table II showed TA-TMA manifestations and associated circumstance of the patient. Conclusion: Our experience suggests that CSA linked TA-TMA is totally different from no CSA linked TA-TMA. The former had good response and prognosis, the later were always associated with GVHD, hypohepatia and virus infectious. The mortality of no CSA linked TA-TMA is high, they had poor prognosis and badly response. Disclosures: No relevant conflicts of interest to declare.

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Complete Resolution of Extensive Chronic Graft-Versus-Host Disease with Ibrutinib

Blood ◽

10.1182/blood.v126.23.5474.5474 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5474-5474

Author(s):

Audrey Scholoff ◽

Gloria Obi ◽

Kelty R. Baker ◽

George Carrum ◽

Rammurti T Kamble

Keyword(s):

Graft Versus Host Disease ◽

Complete Resolution ◽

Conflicts Of Interest ◽

Complete Response ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host ◽

Oral Ulcers

Abstract We herein document a complete response of extensive chronic graft-versus-host disease (cGvHD) to a Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib. A 41 years old female with primary refractory MCL underwent mismatched unrelated donor (MMUD) allogeneic hematopoietic stem cell transplantation in December 2011 (conditioning with CY/TBI and alemtuzumab, graft=6.6x 106/kg CD-34+ cells, tacrolimus alone for GVHD prevention). Following engraftment on day 11, she developed grade III acute GvHD involving the skin and gut on day 17 of transplantation that persisted beyond 100 days post-transplant. Her cGvHD was treated with steroids, but remained active and extensive. Despite persistent cGvHD and 100% donor chimerism she relapsed in July 2012. Treatment with radiation and bendamustine with rituximab failed. By December 2013, the patient had extensive cGvHD manifesting as scleromatous skin thickening, oral ulcers and sclerosis of the buccal mucosa, ocular dryness and diarrhea, and was started on ibrutinib1 560 mg once daily for relapsed MCL. After 8 weeks of therapy, cGvHD had begun to improve. Oral steroids were reduced and ultimately stopped after 26 weeks of ibrutinib; after 30 weeks treatment all cGvHD manifestations resolved completely. A complete remission for MCL was documented at 8 weeks of ibrutinib initiation. Currently she continues to be on 560 mg daily ibrutinib without cGvHD exacerbation or MCL relapse for 22 weeks and 52 weeks, respectively. Chronic graft versus host disease (cGvHD) is mediated donor T cells. The role of B cells in the pathogenesis of cGvHD is increasingly recognized. Two murine studies have explored the role of ibrutinib in cGVHD-like syndromes, one in which there is T cell driven sclerodermatous cGvHD and a second in which there is Ab driven multiorgan system cGvHD that includes bronchiolitis obliterans (BO). Administration of ibrutinib decreased the incidence and severity of sclerodermatous, and improved pre-existing lesions and also improved pulmonary fibrosis and reduced BO. Animals lacking BTK and ITK did not develop cGVHD, indicating that these molecules are critical to cGVHD development. Our report provides the evidence that BTK inhibition led to complete resolution of cGvHD and supports exploration of its role in future clinical trials. Disclosures No relevant conflicts of interest to declare.

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Venous Thromboembolic Disease and Bone Marrow Transplant: A Remarkable Cause of Mortality and Morbidity — Potentially Preventable

Blood ◽

10.1182/blood-2018-99-113780 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5070-5070

Author(s):

Marta Rivas Luque ◽

Estefanía Morente Constantin ◽

Pablo Romero Garcia ◽

Maria Almudena Garcia-Ruiz ◽

Manuel Jurado

Keyword(s):

Medical History ◽

Conflicts Of Interest ◽

Protein S ◽

Marrow Transplant ◽

Morbidity And Mortality ◽

Hematopoietic Stem ◽

Mortality And Morbidity ◽

Vein Thrombosis ◽

Venous Thromboembolic ◽

Hemorrhagic Risk

Abstract Thrombotic events are frequent in patients undergoing HSCT, being an important cause of morbidity and mortality. The highest incidence occurs three months after the transplant. There are several risk factors, which add to those already known for VTE: neoplasia, central venous catheters, immobilization, chemotherapy, infections, GVHD. In the series described, the frequencies are variable, between 0.5 and 23.5%, with an overall incidence of 5%. In patients with GVHD, this incidence increases, with up to 35% of events. METHODS A retrospective observational study that includes patients transplanted in our Unit between 2014 and 2017 has been conducted, with the objective of analyzing the incidence of VTE peri-TPH. Likewise, we have analyzed if it is associated to catheter, presence of CVRF, if there was a known medical history of thrombophilia, number of platelets at time of thrombosis, the heparin used and whether anticoagulation was maintained indefinitely or not. RESULTS Out of the 235 patients included in our series, 130 underwent an autologous transplant and 105 an allogeneic transplant. 18 thrombotic events occurred (9 men and 9 women, aged between 18 and 65 years), which means 7.5% (14 occurred between days 0-100, 12 in patients undergoing autologous hematopoietic stem cell transplantation). Three of them had thromboembolism and the rest deep vein thrombosis, 4 of which with catheter. The platelet count at the time of the event ranges from 21 to 409,000 / mm3. Regarding the heparin used, 2 were treated with Tinzaparin and the rest with Bemiparin. Only 1 of the patients presented prior VTE. Among the patients, there were some with CVRF and others without relevant medical history. Just in one patient, a family thrombophilia study had been performed prior to his hematological diagnosis, resulting in a deficit of protein S. In 8 of the patients, anticoagulation was maintained indefinitely with LMWH in the post-transplant period. CONCLUSIONS Our incidence approaches the literature, albeit the series of published cases are heterogeneous and with variable differences. Although the incidence of thrombosis in these patients is a cause of marked morbidity and mortality, the risk of bleeding also increases, therefore routine prophylaxis is not recommended in all patients. We must undergo an exhaustive analysis of the data to identify individually which patients may be candidates for prophylaxis, with the aim of reducing the incidence without raising the hemorrhagic risk of our patients. Disclosures No relevant conflicts of interest to declare.

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23 Years of Management: A Retrospective Review of Treatment for Aplastic Anemia.

Blood ◽

10.1182/blood.v114.22.1091.1091 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1091-1091

Author(s):

Connie M Piccone ◽

Marie Boorman Martin ◽

Zung Vu Tran ◽

Kim Smith-Whitley

Keyword(s):

Bone Marrow ◽

Aplastic Anemia ◽

Retrospective Review ◽

Pediatric Patients ◽

Conflicts Of Interest ◽

Bone Marrow Failure ◽

Complete Response ◽

Primary Objective ◽

Hematopoietic Stem ◽

Transfusion Independence

Abstract Abstract 1091 Poster Board I-113 Introduction Aplastic anemia (AA) is a syndrome of bone marrow failure characterized by peripheral pancytopenia and marrow hypoplasia. In the past, AA was considered to be a fatal disease; however, current therapies, including bone marrow transplantation or immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CSA), are curative in the majority of patients. IST is effective at restoring hematopoietic stem cell production, but relapse and evolution to myelodysplastic syndromes remain clinical challenges. Additionally, there is no real consensus regarding optimal CSA levels, duration of CSA treatment, or the optimal use of growth factors and their relationship to the development of clonal disease. Objectives The primary objective was to review treatment management for severe AA in pediatric patients in order to elucidate treatment differences and review morbidity and mortality as they relate to treatment variation. Study Design/Methods A retrospective review of pediatric patients treated at the Children's Hospital of Philadelphia for AA (both severe and moderate) over a 23 year period was performed. Results A total of 70 patients with AA were treated at our institution from 1985 to July 2008. Exclusions included: 6 patients who received some type of initial treatment at outside institutions, 4 patients who had missing records, and 2 patients who had a diagnosis of moderate AA. Thus, a total of 58 patient records were included in the analysis. Of the total patients reviewed, 60% were male and 40% were female. 34.5% of patients were African-American, and 57% were diagnosed in 2000 or later. The mean age at diagnosis was 9.5±5.8 years. 52% fell into the category of very severe AA based on published diagnostic criteria, 45% had severe AA, and 2 patients (3%) had moderate AA. 15.5% of patients developed AA in the setting of acute hepatitis. More than half of the patients treated with IST had a complete response (CR). The average time to CR was 15±15 months. Average duration of CSA treatment was 15±13 months and 8.6±10.7 months for growth factor. Two patients (3.5%) died, one from complications unrelated to AA and one from infectious complications post-BMT after initial IST failure. Average time to transfusion independence for all patients was 8±11 months (with a range of 0-54 months). Not surprisingly, the time to transfusion independence was significantly associated with IST failure (p=0.010). Patients who failed treatment had an average time to transfusion independence of 17±16 months as compared to those who were complete responders who had an average time to transfusion independence of 3±3 months. Additionally, there was a significant association between IST failure and CSA levels (p=0.014). Patients who had nontherapeutic CSA levels overall had an increased rate of treatment failure. Of those patients who were nontherapeutic, 56% were noncompliant with CSA administration. There was no significant association between IST failure and bone marrow cellularity (p=0.251). PNH was diagnosed in 5% of patients; there were no patients with evidence of myelodysplastic syndrome (MDS). Two of the 3 patients with PNH failed initial IST. Another 2 patients had evidence of a cytogenetic abnormality (16q deletion), but never progressed to MDS. (Note: averages presented as mean±SD) Conclusions/Methods With current IST regimens, AA is curative in the majority of pediatric patients. IST failure was associated with nonadherence to CSA treatment. For patients with confirmed clonal disease, it is possible that IST failure and the ultimate development of clonal disease are related. Disclosures No relevant conflicts of interest to declare.

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HHV-6 Encephalitis in Pediatric Unrelated Umbilical Cord Blood Transplantation: Role for Ganciclovir Prophylaxis?

Blood ◽

10.1182/blood.v114.22.4667.4667 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4667-4667

Author(s):

Frankie Wai Tsoi Cheng ◽

Vincent Lee ◽

Wing Kwan Leung ◽

Paul Kay Sheung Chan ◽

Ting Fan Leung ◽

...

Keyword(s):

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Conflicts Of Interest ◽

Rare Complication ◽

Cord Blood Transplantation ◽

The Other ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Before And After

Abstract Abstract 4667 Background The role of ganciclovir as HHV-6 prophylaxis in unrelated hematopoietic stem cell transplant (HSCT) setting remains controversial. Methods We performed a 8-year retrospective review of patients received unrelated HSCT from January 2000 to September 2008. From January 2002, ganciclovir prophylaxis 5mg/kg twice daily for 7 days for all unrelated HSCT before transplant was adopted. The other transplant policies including antibacterial, antifungal, antiviral and graft-versus-host disease control policies remained unchange in that period. The prevalence of HHV-6 encephalitis was studied before and after the change in policy. Result Fifty-four unrelated HSCT were performed from January, 2000 to September, 2008. Total four cases (7.4%) of HHV-6 encephalitis were diagnosed. Two cases out of 16 cases (12.5%) diagnosed before adoption of the policy; 2 cases out of 38 cases (5.3%) diagnosed afterward. All of them were unrelated umbilical cord blood (UCB) transplant recipients. Two cases had significant residual neurological deficit and refractory seizure. The other two cases died of other transplant-related mortalities. Conclusion We conclude that HHV-6 encephalitis is still a rare complication of unrelated HSCT and may be more common in unrelated UCB transplantation. Routine use of ganciclovir as HHV-6 prophylaxis in all unrelated HSCT recipients may not be justified. Disclosures: No relevant conflicts of interest to declare.

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First Asia-Pacific Co-Operative Multicenter Multiple Myeloma Clinical Trial: Preliminary Results of the “dtZ”/“DAZZLE” Study.

Blood ◽

10.1182/blood.v114.22.4940.4940 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4940-4940

Author(s):

Gerrard Teoh ◽

Kihyun Kim ◽

Alok Srivastava ◽

Vasant Pai ◽

Sung-Soo Yoon ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Conflicts Of Interest ◽

Complete Response ◽

Osteonecrosis Of The Jaw ◽

High Rate ◽

Asia Pacific ◽

Hematopoietic Stem ◽

Asian Patients ◽

Tract Infections

Abstract Abstract 4940 Introduction Many physicians have anecdotally reported that Asian patients with multiple myeloma (MM) are frequently unable to tolerate full doses of dexamethasone (Dex) and/or thalidomide (Thal). Unfortunately, co-operative clinical studies from the Asia-Pacific countries are presently lacking and the effective dose of the Dex/Thal combination in Asians is unknown. Since higher doses of zoledronic acid (Zol) have been shown to exert an anti-MM effect in pre-clinical models of MM, we investigated whether higher frequency dosing of Zol combined with lower doses of Dex/Thal could be an effective and better tolerated regimen in Asian patients. Moreover, since attainment of very good partial response (VGPR), near complete response (nCR) or complete response (CR) prior to autologous hematopoietic stem cell transplantation (AHSCT) correlates with good outcome in MM, we wanted to determine if this lower-dose Dex/Thal with higher-frequency dosing Zol regimen could be a good preparative regimen in transplant-eligible patients. Patients and Methods In this international co-operative multicenter phase II non-randomized single arm study in previously untreated patients with MM (n=44), all patients received up to 6 cycles of three-weekly Dex/Thal/Zol (or “dtZ”). Doses of Dex ranged from 20 mg weekly to 20 mg four times a week; and doses of Thal ranged from 50 mg weekly to 100 mg every night. Zol 4 mg was given three-weekly. Response was graded using Blade's criteria. Results The study population included 67.3% Oriental (Korean and Chinese), 30.8% Indian and 1.9% Malay patients. 15.4% of patients were ISS stage I, 61.5% stage II and 23.1% stage III prior to treatment. 39 (88.6%) patients demonstrated at least a partial response (PR); and 23 (52.3%) of patients achieved VGPR (18.2%), near nCR (15.9%) or CR (18.2%). The fastest time to VGPR/nCR/CR was 1 cycle. Most patients tolerated treatment very well and were managed in the outpatient clinic. Sepsis was the most frequently reported grade 3 or 4 toxicity – 8 (18.2%) patients developed bronchopneumonia, and 3 (6.8%) gastrointestinal or urinary tract infections. 1 (2.3%) patient was suspected of having pulmonary embolism. There were 4 (9.1%) deaths – 3 from severe sepsis and 1 from an unknown cause. Importantly, there were no reports of peripheral neuropathy, osteonecrosis of the jaw (ONJ) or end stage renal failure. In fact, there was an overall 2.4% improvement in the median creatinine clearance time (CCT). Finally, the percentage of CD34 stem cells was not adversely affected by treatment with dtZ. Conclusions The dtZ regimen appears to be an effective and well-tolerated treatment regimen for Asian patients with newly-diagnosed MM. The high rate of VGPR/nCR/CR will greatly facilitate AHSCT in transplant-eligible patients. Judicious use of low-dose Thal has abrogated the numerous side-effects associated with Thal and greatly improved patient tolerance. Even though Zol is administered at a higher frequency, it is not associated with worsening of renal function or ONJ. Infections are the most frequent and worrisome complications of treatment. These are likely to be related to the dose of Dex. Accordingly, it is probably wise to further lower the dose of Dex in future studies. (This study is registered with NIH PRS # 00263484.) Disclosures No relevant conflicts of interest to declare.

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Correlation Between Severity of cGvHD and Transplant Outcome: A Retrospective Monocenter Study Based on NIH Classification,

Blood ◽

10.1182/blood.v118.21.4088.4088 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4088-4088

Author(s):

Colombe Saillard ◽

Roberto Crocchiolo ◽

Sabine Furst ◽

Jean El-Cheikh ◽

Luca Castagna ◽

...

Keyword(s):

Stem Cells ◽

Disease Risk ◽

Conflicts Of Interest ◽

Immunosuppressive Treatment ◽

Conditioning Regimen ◽

Unrelated Donor ◽

Extensive Form ◽

Hematopoietic Stem ◽

Transplant Outcome ◽

Significant Difference

Abstract Abstract 4088 Background: Chronic graft-versus-host disease (cGvHD) after allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies is associated with lower relapse rate, due to graft-versus-tumor effect. We know that the extensive form is associated with higher transplant-related mortality after myeloablative conditioning regimen, mainly due to infectious complications as a consequence of immunosuppressive treatment. Beside the “classical” Seattle classification (limited or extensive form), a recent classification (from National Institute of Health, NIH) distinguishes three levels of severity: limited, moderate and severe. We compare here both classifications for patients receiving reduced-intensity conditioning (RIC) transplant and looked for any association of cGvHD severity with transplant outcome. Patients and Methods: We evaluated data on all adult patients with hematological lymphoid or myeloid malignancies who received HSCT from related or unrelated donor, using peripheral blood stem cells, after RIC regimens (with fludarabine-busulfan-ATG) between 1998 and 2010 at the Institut Paoli-Calmettes (Marseille, France). Data on main pre- and post-transplant variables were collected; cGvHD was classified according to its presentation and severity (with both Seattle and NIH classifications) and was correlated with overall survival (OS), non relapse mortality (NRM), and relapse. cGvHD was considered as time-dependent variable, and was included in uni- and multivariate models, after adjusting for age, disease risk, HLA compatibility, graft source and comorbidity score. Relapse or death before cGvHD was considered as a competing event. Results: 283 patients were evaluated, 121 have developed cGvHD (27 limited forms and 94 extensive forms), 162 have not, for an incidence rate of 10% and 33% of limited and extensive forms respectively. Median follow up was 607 days, patients had a median age of 50 years, transplanted for acute leukemia (55), lymphoma (78), multiple myeloma (49), myelodysplastic syndrome (24), CLL (12), CML (16) or others malignancies (19). Peripheral stem cells were mostly used (294 versus 20 bone marrow graft). We had 241 related donors and 77 unrelated donors. The median day of cGvHD occurrence was 132, we found 52 de novo forms, 40 quiescent and 26 progressive forms. After reclassification with NIH criteria, we obtained 28 mild, 52 moderate and 41 severe forms. 22 of 27 limited forms were classified as mild, the extensive forms were divided into 49 moderate and 39 severe forms. In multivariate analysis, mild and moderate forms were associated with better OS compared with other groups. Severe cGvHD was associated with significant increase in NRM. Among the other variables, only age was statistically significative in OS and NRM models. Although the incidence of relapse was lower in patients with cGvHD compared with those without, no significant difference was seen between the 3 groups of patients presenting it. Conclusion: Following a fludarabine-busulfan-ATG RIC, it seems that mild to moderate cGVHD forms are associated with better OS than patients without or with severe cGVHD. This is related to lower NRM than patients with severe cGVHD and at least a comparable antitumoral effect with respect to patients without cGVHD. This invites developing strategies limiting severity but not abrogating the effect of cGVHD. Disclosures: No relevant conflicts of interest to declare.

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Favorable Results of Allo-HSCT from MRD in Patients with Myelofibrosis

Blood ◽

10.1182/blood.v124.21.5934.5934 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5934-5934

Author(s):

Miroslaw Markiewicz ◽

Monika Dzierzak-Mietla ◽

Patrycja Zielinska ◽

Agata Wieczorkiewicz-Kabut ◽

Sylwia Mizia ◽

...

Keyword(s):

Bone Marrow ◽

Collagen Type ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Graft Loss ◽

Chronic Phase ◽

Curative Treatment ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Post Transplant

Abstract Introduction: Myelofibrosis (MF), chronic myeloid malignancy associated with shortened survival, in majority of patients develops de novo as Primary MF, but also polycythemia vera (PV) or essential thrombocythemia (ET) may progress into post-PV or post-ET MF. Although management of MF includes several treatment options, the only potentially curative treatment approach in MF is allogeneic hematopoietic stem cell transplantation (allo-HSCT). Aim of this study was to evaluate the results of allo-HSCT in patients with MF treated in Katowice, Poland. Material and Methods: 27 pts (14 male and 13 female) with median age 51 years (range 21–63) were treated with allo-HCT due to PMF (20), post-PV (4) or post-ET (3) MF. 11,7,11,26 and 41% of pts had DIPSS 0,1,2,3 and 4, respectively. Median bone marrow cellularity was 70% (10-100%), fibrosis was collagen-type (14 pts including 2 with osteosclerosis), reticulin (10) or it was not specified (3). Splenomegaly was present in all pts: 13-20 cm (14 pts), > 20 cm (13 pts). JAK2V617F point mutation was present in 18 pts. Karyotype was available in 14 pts: in 9 normal, in 5 with variable abnormalities. Median time from diagnosis to allo-HCT was 1.5 (0.4–9.5) years. 16 pts (59.3%) received cells from HLA-matched related donor (MRD), 11 pts (40.7%) from unrelated donor: 10/10 (9) or 9/10 (2) HLA-A,B,C,DR,DQ alleles matched. Reduced intensity conditioning (RIC) was used in 26 pts, 1 patient received myeloablative conditioning (MC). Sources of stem cells were: peripheral blood (21), bone marrow (4) and both (2). All pts but one had chronic phase of MF at time of transplantation. Results: 14/27 (52%) pts are alive at median 3.4 (0.4-5.4) years after allo-HSCT: 11/16(69%) from MRD and 3/11(27%) from MUD, p=0.032. Graft failure, graft loss or PRCA were observed in 3, 5 and 1 pt, respectively. Absolute neutrophil count >0.5×109/L and platelet count >50×109/L were achieved at median 16 and 28 days, respectively. 12/27 (44%) pts reached complete blood count of Hb>10 g/dl, Plt>100 G/l and WBC>3.5 G/l; 11 of them (92%) are alive. 6/27 (22%) pts remained either RBC or PLT transfusions dependent post-transplant; 3 of them (50%) died. 9/27 (33%) pts remained both RBC and PLT transfusion dependent and all of them died. JAK2V617F mutation was completely eradicated in 11/16 evaluated previously positive patients (69%), decreased in 4 (25%) and stable in 1(6%) pt. Acute graft-versus-host disease (aGVHD) III-IV developed in 5/27 (19%) and extensive chronic GVHD in 5/19 (26%) pts. Relapse occurred in 4 pts and was treated with subsequent second transplant (in 1 pt thereafter by 3-rd allo-HSCT). Spleen length decreased at median by 5 (0.3-9.2) cm. Out of 7 pts with initial collagen fibrosis who were evaluated post-transplant, 1 had no fibrosis, 5 reticulin type and only in 1 pt collagen fibrosis was stable. Out of 3 pts with initial reticulin fibrosis it disappeared in 2 and progressed to collagen type in 1. Causes of death were GVHD (5 pts: 3 aGVHD, 2 cGVHD) and pancytopenia with either infection (7 pts) or CNS hemorrhage (1 pt). Conclusions: Allo-HSCT, the only curative treatment of myelofibrosis, provides chance of long survival, regression of the disease (lower stage of fibrosis, JAK2V617F eradication) and improved quality of life (transfusion independency, decreased splenomegaly). Transfusion independency may indicate good outcome. Favorable results are observed after allo-HSCT from MRD. Disclosures No relevant conflicts of interest to declare.

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HLA and Kir Mismatch Transplant Affect Cytopenia Beyond Day 28 after Thalassemia Transplant: A Primary Manifestation of Chronic Graft Versus Host Disease

Blood ◽

10.1182/blood.v124.21.5929.5929 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5929-5929

Author(s):

Xiaohui Zhou ◽

Chunfu Li ◽

Jianyun Liao ◽

Xiangjun Liu

Keyword(s):

Conflicts Of Interest ◽

Hla Class I ◽

Thalassemia Major ◽

Class I ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Graft Versus Host ◽

Hla Antibody ◽

Cmv Status

Abstract Background Cytopenia beyond day 28 post-transplant (CB-28PT) following hematopoietic stem cell transplantation (HSCT) with β-thalassemia major (TM) rarely was reported. The exact mechanism for the development of CB-28PT is not well known. Aim To find out causes of CB-28PT cytopenia. Method We retrospectively analyzed data (HLA mismatch status, HLA antibody status of patients, KIR gene mismatch status, KIR-ligand matching status, donor/patient CMV status, donor/patient age and sex) of 93 TM patients underwent HLA 8/8 fully matched or 7/8 matched unrelated donor HSCT. All the patients used sole NF-08-TM protocol with median follow-up time of 19 (r: 2-44) months. Results Results show a significant association between DRB1 mismatch and CB-28PT (P = 0.012). In addition, presence of Class I HLA antibody in the patient’s sera seems increase the chance of CB-28PT. Finally, the matching between inhibitory KIR2DL1 and their corresponding ligand HLA-C2 has a protective effect for CB-28PT. Conclusion We propose that CB-28PT may be a primary manifestation of cGVHD in pediatric TM patients undergoing HSCT positive influenced by HLA DRB1 mismatch, HLA class I antibody and negatively affected by KIR-ligand match. Disclosures No relevant conflicts of interest to declare.

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Low Density Granulocytes in Patients after Allogeneic Hematopoietic Stem Cells Transplantation (allo-HSCT): A Distinct Class of Neutrophils in Systemic Alloimmunity

Blood ◽

10.1182/blood.v126.23.4614.4614 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4614-4614

Author(s):

Ekaterina Mikhaltsova ◽

Valeri G. Savchenko ◽

Larisa A. Kuzmina ◽

Mikhail Drokov ◽

Vera Vasilyeva ◽

...

Keyword(s):

Lupus Erythematosus ◽

Peripheral Blood ◽

Hematological Malignancies ◽

Mononuclear Cells ◽

Conflicts Of Interest ◽

Human Peripheral Blood ◽

Unrelated Donor ◽

Low Density ◽

Hematopoietic Stem

Abstract Introduction It's generally considered that all alloimmune process such as acute graft-versus host disease (aGVHD) after allo-HSCT are mostly controlled by lymphocytes. The role of neutrophils in systemic alloimmunity after allo-HSCT is still illusive. In 1987 a distinct subset of proinflammatory, low-density granulocytes (LDGs) isolated from the peripheral blood mononuclear cell fractions of patients with system lupus erythematosus has been described. There is no LDG's in healthy donors. While the origin and role of LDGs still needs to be fully characterized, we try to describe this population in patients with hematological malignancies after allo-HSCT Patients and methods. Peripheral blood samples were collected in EDTA-tubes before allo-HSCT, on day +30,+60,+90 after allo-HSCT and at day of aGVHD from 47 patients with hematological malignancies (AML=22, ALL n=17, LPD=3, MDS =2; CML=2; 17 with active disease, 30 - in CR) after allo-HSCT (from matched unrelated donor n=34, from matched related donor n=13; MAC = 13, RIC=34). Isolation of mononuclear cells from human peripheral blood was made by standard protocol using Lympholyte®-M Cell Separation Media (Cedarlane Labs). The anti-CD66b-PE (Biolegend, USA) antibodies and FSC/SSC were used to determine LDGs cells as FSChigh \SSChigh \CD66b+. 100000 of cells were analyzed on a BD FACSCanto II (Becton Dickinson, USA). Results. Results of blood evaluation of 47 patients with hematological malignancies, whose blood was examined after allo-HSCT presented in table 1. Conclusion Despite the fact that we don't get significant differences. LDG's detection in allo-HSCT patients need further investigation. Table 1. Incidence of LDG after allo-HSCT in patients with and without aGVHD Table 1. Incidence of LDG after allo-HSCT in patients with and without aGVHD Disclosures No relevant conflicts of interest to declare.

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