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  • 1
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3113-3113
    Abstract: The function of NK cells is regulated by a balance between signals transmitted via actvating and inhibitory receptors, including killer-immunoglobulin-like receptors (KIRs). Activating KIRs (KIR2DS1 and KIR2DS2) are also present on subsets of T cells, which has recently been demonstrated to play a role in several autoimmune conditions. The goal of this analysis was to determine the relationship between donor activating KIRs genotype and outcome after unrelated donor hematopoietic stem cell transplantation (URD-HSCT). Seventy five patients (age 30y; range 14–57) with hematological malignancies treated with URD-HSCT in a single centre between 2000 and 2006 were included in the analysis. Donors were selected using DNA-high resolution typing for both HLA class I and II alleles. KIR2DS1 and KIR2DS2 genes were examined in all donors. Additionally, in 16 cases a subpopulation of KIR2DS2/DL2/DL3-positive T cells in peripheral blood was monitored in donors as well as in recipients for 6 months after transplantation. The conditioning regimen was myeloablative and based on chemotherapy alone (n=56) or TBI (n=19). Graft-vs-host disease (GVHD) prophylaxis was uniform and consisted of cyclosporin, methotrexate, and pre-transplant anti-thymocyte globulin. Twenty-five % of donors were positive for both KIR2DS1 and KIR2DS2 gene, 18% were positive for KIR2DS1 only, 25% - for KIR2DS2 only, and 32% were negative for both KIR2DS1 and KIR2DS2. In univariate and multivariate analysis, including other potential risk factors, the presence of both KIR2DS1 and KIR2DS2 genes of the donor was associated with decreased overall survival (0% vs. 80%, RR 3.2, p=0,01) and disease free survival (0% vs. 64%, RR 2.5, p=0,03), compared to the remaining subgroups. Furthermore, simultanous KIR2DS1 and KIR2DS2 positivity resulted in increased GVHD-related mortality (70% vs. 8%, p=0.01) in univariate analysis (incidence of both acute and chronic GVHD contributed to this effect). KIR2DS2/DL2/DL3-positive T cells were detected in 3/16 donors before URD-HSCT and in all recipients between day +28 and +180 after URD-HSCT. KIR-positive T cells were particularily frequent (32%–42% of all CD3 cells) in three patients who developed acute GVHD, and for whom the donors were KIR2DS2-positive. We conclude that the simultaneous presence of both KIR2DS1 and KIR2DS2 in the donor is associated with decreased survival following URD-HSCT. The mortality may result from higher incidence of lethal GVHD. Preliminary observation suggests the role of KIR-bearing T lymphocytes in this effect.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3156-3156
    Abstract: Factors contributing to relapses and GVHD following allogeneic Hematopoietic Stem Cell Transplantations (HSCT) from HLA-matched unrelated donors are not well established. We analyzed 35 patients (pts) transplanted from HLA 10/10 alleles (A, B, C, DRB1, DQB1) matched unrelated donors (URD) in the Dept. of Hematology and BMT, Katowice, Poland, with use of the same standard operating procedure from January 2004 until March 2006. Indication for HSCT was AML (13 pts), ALL (8), CML (7), MDS (2), PNH (3), CLL (1), myeloid sarcoma (1). Preparative regimen was Treosulfan+Fludarabine (23 pts), TBI+Cy (9) and Bu+Cy (3). Alleles encoding 11 minor Histocompatibility Antigens (mHA: HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, HwA-9, HwA-10, UGT2B17, HY) were analyzed for each donor-recipient pair with use of Dynal AllSet mHA typing kit and PCR-SSP method. Only immunogenic mHA mismatches were analyzed. Information on whether mHA mismatches might result in Host-versus-Graft or Graft-versus-Host responses was established with use of the minor Histocompatibility Knowledge Database of Leiden University Medical Center’s minor Histocompatibility Workshop. Patients transplanted from donors with mHA mismatched in HVG direction had significantly higher probability of relapse (64+/− 8% versus 10+/− 9%, p=0.003) when compared to pairs without mHA HVG immonogenicity. Patients transplanted from donors with mHA mismatched in GVH direction had higher probability of aGVHD (88+/− 8% versus 53+/− 11%, p=0.14) and cGVHD (41+/− 16% versus 37+/− 17%, p=0.65) when compared to pairs without GVH immunogenicity. GVHD was also observed more often on day +100 (33% versus 6%, p=0.06) when mHA mismatch in GVH direction was present. Observed influence of HVG and GVH immonogenicity on probability of relapse and GVHD did not lead to significantly different survival in observed groups of pts. These results indicate that mHA immunogenic mismatches in HVG and GVH direction may be responsible for relapse and GVHD, respectively, in HSCT recipients from HLA-matched unrelated donors. The study is being continued to confirm these primary observations and to establish the associations of specific mHA mismatches with HSCT outcomes. Impact of mHA mismatch on probability of relapse and GVHD Immunogenicity of mHA mismatches HVG no HVG p # of patients 18 17 Relapse at 1 year 64%+/−8 10%+/−9 0.003 Immunogenicity of mHA mismatches GVH no GVH p # of patients 16 19 aGVHD 88%+/− 8 53%+/−11 0.14 cGVHD at 1 year 41%+/−16 37%+/−17 0.65 Impact of mHA mismatch on probability of survival Immunogenicity of mHA mismatches HVG GVH only HVG only GVH no HVG no GVH p # of patients 9 9 7 10 Survival at 9 months 63%+/−17 57%+/−25 83%+/−15 69%+/−15 0.86
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 5394-5394
    Abstract: Extramedullary (EM) relapses of acute leukaemia (AL) without concomitant bone marrow (BM) involvement are rare after allogeneic hematopoietic stem cell transplantation (alloHSCT) and little is known about their incidence in larger series of patients (pts) and long-term outcome. We retrospectively analysed this mode of leukemia recurrence in a cohort of 220 consecutive pts with AL (88 with ALL, 132 with AML) who underwent alloHSCT in our institution between June 1993 and May 2005. 5 out of 48 pts who relapsed (4 B-line ALL, 1 45 X, -Y, t,(8;21) AML, F/M 4/1, median age 29 years, range 28–38 years) developed isolated EM infiltrates after a median time of 13 months (range, 8–23 months) post alloHSCT. There was no evidence of leukaemic BM involvement at relapse in 5/5 pts. We revealed complete donor chimerism in 4/4 studied pts. The leukaemic origin of pathologic massess was confirmed in each case by immunohistochemical methods or flow cytometry with the use of appropriate combination of the following markers: CD10, CD19, CD20, CD45, CD79a, CD34, TdT, MPO. Our data indicate that isolated EM disease following alloBMT affects predominantly high-risk ALL pts. Sites of EM relapses varies widely among the pts, however, in most of them are localised outside the well-defined sanctuaries (i.e. CNS or testis). Local radiation therapy seems to be the most effective treatment option, however, the long-term ouctomes of the pts with EM tumors remain poor. According to our experience in selected pts individualized menagement, such as intraarterially administered anthracyclines or “total skin irradiation” may be of value. Characteristics and clinical course of pts with isolated EM relapse post alloHSCT are summarized in the table below. The extramedullar relapses after AlloHSCT Patient no Age/sex Disease/subtype, cytogenetics Sites of relapse (post-allHSCT months) Treatment after relapse Survival post relapse (months) Outcome ND = not done, CNS = central nervous system, DLI = donor lymphocyte infusion 1 30/F ALL/CD10+; t(9;22) skin of the head (13) imatinib, chemotherapy 18 Progressive disease with systemic relapse; hypoplastic death following induction 2 29/F ALL/pre-pre B, ND Left distal tibia with soft tissue (23), then soft tissues of the left hand, right forearm, skin at various sites, cervical and axillary lymph nodes (30-52) Radiotherapy (including “total skin irradiation”), IFN-alpha, DLI, daunorubicine injections to the left femoral artery, chemotherapy 30 Systemic relapse; hypoplastic death following palliative chemotherapy 3 28/F ALL/pre-preB; t(4;11) Subcutaneous tissue of the left arm (17) Radiotherapy, oral cytostatics (mercaptopurine, methotrexate), IFN-alpha 17 Systemic relapse, death during induction treatment due to pneumonia 4 28/F ALL/CD10+;t(9;22) CNS, leptomeningeal (8) Chemotherapy (high-dose cytarabine), methotrexate +steroids intrathecally, imatinib 10 Death due to fulminant gastrointestinal infection 5 38/M AML/M2, 45, X,-Y, t(8;21) Small intestine and the root of mesentery (8) Surgery 1 Immediate systemic relapse; death due to infectious complications
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 5444-5444
    Abstract: The significance of additional transplant-related risk factors for hemolysis, including potentially severe hemolysis due to Kidd group incompatibility, is unknown in BMT from matched unrelated donors (MUD). We report MUD BMT for 35y old male PNH patient (pt) diagnosed 1,5y before, with CD59 defect on 95% of erythrocytes (Er), with refractory hemolysis (LDH 1886 U/l, haptoglobin 0.08 g/l) and IgG autoantibodies on Er, previously treated with steroids and multiple transfusions with increasing frequency. BMT-related risk factors for hemolysis were: major Kidd incompatibility (Jk(b)+ donor and detectable anti-Jk(b) alloantibodies in titer 2 in pt), minor AB0 incompatibility (pt B, donor 0 with anti-B titer 1:16) and different Rh (pt−, donor+). Other risk factors included CMV seronegativity of the donor and seropositivity of the pt, arterial hypertension, steroid-related diabetes mellitus and probable former thrombotic episode leading to nasal septum perforation. MUD was ten alleles HLA-matched 38y old male. Myeloablative conditioning consisted of Treosulfan, Fludarabine and Thymoglobulin. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin-A and methotrexate. Gancyclovir and IgG were used for CMV-reactivation prophylaxis. Transplanted bone marrow was depleted of Er on Fenwall CS3000 plus and contained 0.5x10(8) NC/kg, 2.1x10(6) CD34+ cells/kg and 12.5x10(6) CD3+ cells/kg. No serious complications were observed during the treatment and post-transplant aplasia. Filtered washed Er 0Rh-Jk(b)- were transfused 7x and single-donor platelets 7x. Following 11 days of absolute agranulocytosis full reconstitution of haematopoiesis was achieved with granulocyte count of 1.0x10(9)/l and platelets 50x10(9)/l on day +22, Hb 10 g/dl on day +26. Acute GVHD grade II was transiently present since day +21 and responded well to low-dose methylprednisolone. No chronic GVHD was observed. CMV reactivation with transient severe pancytopenia developed after day +70 and was overcome with ganciclovir, foscarnet and immunoglobulins. Hemolysis gradually decreased (LDH less than 400 U/L since day +5, normal haptoglobin & gt;0.7 g/l since day +38). Anti-Jk(b) alloantibodies titer reached 0 on day +31 and since then they were detectable only with use of a micro-method. Full 100% donor chimerism was achieved on day +28 and was re-confirmed on days +71 and +99. Recipient-type population of erythrocytes gradually decreased (24%, 7% and 1% on days +30, +70 and +98, respectively). Complete eradication of PNH clone was confirmed by absence of complement inhibitor CD55 (DAF) and CD59 (MIRL) defects on 100% of erythrocytes and granulocytes in flow-cytometric evaluation performed on day +160. The patient stays at home without any signs of GVHD, hemolysis nor PNH over 9 months following BMT. We conclude that MUD BMT can be offered as an effective treatment option despite multiple transplant-related risk factors for hemolysis including Kidd group incompatibility.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 2948-2948
    Abstract: Unrelated donor - hematopoietic stem cell transplantation (URD-HSCT) is the treatment of proved long-term efficacy for chronic myeloid leukemia (CML) patients not having an HLA-identical sibling. However, high procedure-related toxicity observed after oral busulfan- or TBI-based conditioning limits its applicability and deteriorates outcome [Radich, Blood2003, 102, 31–5]. This is of increasing importance in the presence of challanging options offered by tyrosine kinase inhibitors. Between 2003–2006 we introduced a new preparetive regimen consisting of Treosulfan (a soluble alkylyting agent) 14 g/m2/d on days -6, -5, -4, Fludarabine 30 mg/m2/d on days -6, -5, -4, -3, -2, and, anti-thymocyte globulin (ATG) at a total dose of 6 mg/kg. Thirty patients (age 32, range 16–48 years) with CML in the 1st chronic phase (n=29) or in 2nd chronic phase (n=1) were included in the study. Median interval from diagnosis to alloHSCT equaled 1.0 (0.5–12.0) years. 63% of patients had previously been treated with Imatinib. The donors were selected based on high resolution typing for both HLA class I and II. 43% of donors were mismatched for a single HLA-C (n=9), HLA-DQB1 (n=3) or HLA-B locus (n=1). Bone marrow was used a source of stem cells in 19 patients, peripheral blood - in 11 cases. GVHD prophylaxis consisted of Cyclosporin A and short-course Methotrexate. All patients engrafted with the median time to neutrophil recovery 〉 0.5 G/L and PLT 〉 50 G/L of 19 (10–30) days and 18 (12–29) days, respectively. Complete donor chimerism was achieved until day +100 in all but one patient. Grade 3–4 neutropenic infections occurred in 13% of patients. Grade 3–4 mucositis as well as hepatic toxicity including VOD were not observed. The incidence of grade II acute GVHD was 23%, whereas grade III-IV acute GVHD was not observed. The incidence of extensive chronic GVHD was 10%. At 3 years the probability of the overall survival and hematological relapse-free survival equaled 82% (+/−7%). The cumulative incidence of non-relapse moratlity was 18% (+/−7%) (fungal infection n=3, bacterial infection n=1, EBV-LPD n=1). Four patients required donor lymphocyte infusion or additional interferon or imatinib treatment because of incomplete donor chimerism or molecular/cytogenetic relapse after initial response. We conclude that treosulfan + fludarabine + ATG conditioning is associated with low organ toxicity, low incidence of severe GVHD and NRM. The regimen is feasible option for CML patients referred for URD-HSCT in tyrosine kinase inhibitors era.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    Online Resource
    Online Resource
    VM Media Group sp. z o.o ; 2018
    In:  Nowotwory. Journal of Oncology Vol. 68, No. 2 ( 2018-08-08), p. 97-100
    In: Nowotwory. Journal of Oncology, VM Media Group sp. z o.o, Vol. 68, No. 2 ( 2018-08-08), p. 97-100
    Type of Medium: Online Resource
    ISSN: 2300-2115 , 0029-540X
    Language: Unknown
    Publisher: VM Media Group sp. z o.o
    Publication Date: 2018
    detail.hit.zdb_id: 2595174-9
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  • 7
    Online Resource
    Online Resource
    VM Media Group sp. z o.o ; 2016
    In:  Nowotwory. Journal of Oncology Vol. 66, No. 2 ( 2016-06-03), p. 160-166
    In: Nowotwory. Journal of Oncology, VM Media Group sp. z o.o, Vol. 66, No. 2 ( 2016-06-03), p. 160-166
    Type of Medium: Online Resource
    ISSN: 2300-2115 , 0029-540X
    Language: Unknown
    Publisher: VM Media Group sp. z o.o
    Publication Date: 2016
    detail.hit.zdb_id: 2595174-9
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  • 8
    In: Biomedicines, MDPI AG, Vol. 11, No. 7 ( 2023-07-18), p. 2014-
    Abstract: The prediction of colorectal cancer (CRC) response to palliative chemotherapy (CTH) is still difficult. Patients at a higher risk of progression may benefit from more aggressive treatment. This study assessed the predictive value of prolactin (PRL) and a panel of cytokines, chemokines, and growth factors for the risk of rapid progression in CRC patients starting palliative CTH. This study included 51 CRC patients initiating palliative CTH with up to 5-year follow-up, divided into rapid and non-rapid progressors. Serum samples were collected before CTH for assessment of a large panel of cytokines, chemokines, growth factors, and PRL via a multiplex method. Rapid progressors (N = 19) were characterized by increased baseline values of IL-8 and IP10 but decreased PRL levels. In addition, PRL below 18.2 ng/mL was a strong predictor of weight loss during CTH. Grade 3 (HR = 2.97; 95%CI: 1.48–5.98) and PRL level (HR = 0.96; 95%CI: 0.91–1.01) were independent risk factors of progression. We showed that CRC rapid progressors are characterized by decreased baseline PRL levels. In addition, increased baseline levels of IP-10, sHER-2, IL-6, and IL-8 may be associated with longer survival; however, larger studies are needed to confirm their predictive role in CRC patients.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2720867-9
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  • 9
    In: The Prostate, Wiley, Vol. 73, No. 5 ( 2013-04), p. 542-548
    Abstract: The G84E mutation in the HOXB13 gene has been associated with a high lifetime risk of prostate cancer in North America (about 20‐fold). The geographical and ethnic extent of this recurrent allele has not yet been determined. METHODS We assayed for the presence of the G84E mutation in 3,515 prostate cancer patients and 2,604 controls from Poland and estimated the odds ratio for prostate cancer associated with the allele. RESULTS The G84E mutation was detected in 3 of 2,604 (0.1%) individuals from the general population in Poland and in 20 of 3,515 (0.6%) men with prostate cancer (Odds ratio [OR] = 5.0; 95% CI: 1.5–16.7; P = 0.008). The allele was present in 4 of 416 (1.0%) men with familial prostate cancer (OR = 8.4, 95% CI: 1.9–37.7; P = 0.005). CONCLUSIONS The G84E mutation predisposes to prostate cancer in Poland, but accounts for only a small proportion of cases. We expect that the G84E founder mutation might be present in other Slavic populations. Prostate 73: 542–548, 2013. © 2013 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 0270-4137 , 1097-0045
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 1494709-2
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  • 10
    Online Resource
    Online Resource
    Walter de Gruyter GmbH ; 2016
    In:  Postępy Higieny i Medycyny Doświadczalnej Vol. 70 ( 2016-5-21), p. 534-541
    In: Postępy Higieny i Medycyny Doświadczalnej, Walter de Gruyter GmbH, Vol. 70 ( 2016-5-21), p. 534-541
    Type of Medium: Online Resource
    ISSN: 1732-2693
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2016
    detail.hit.zdb_id: 2150116-6
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