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This retrospective study analyses the impact HLA heterozygosity, supertypes, and alleles have on incidence of graft versus host disease (GvHD), relapse, overall survival (OS), disease-free survival (DFS) and transplant-related mortality (TRM) after HSCT. The study included patients who underwent HSCT, typed at allele resolution level for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci. The analysis performed on the entire patient cohort (N = 232) showed that HLA-B07 supertype positive patients demonstrated decreased incidence of relapse, better OS and DFS in comparison to those negative for HLA-B07 supertype. Further, a higher incidence of TRM was observed among patients positive for HLA-B27 supertype. Significant association of the HLA-A*02:01 allele presence with decreased incidence of GvHD was found. The occurrence of HLA-A*11:01 allele was associated with a worse OS, DFS and a higher rate of TRM. The analysis of the subgroup of patients with AML or MDS (N = 148) showed an association of HLA-A24 supertype with a worse OS. The HLA-B07 supertype positive patients demonstrated a lower incidence of relapse and a better DFS. A decline in OS and a higher TRM rate were observed among patients positive for HLA-B27 supertype. The presence of HLA-A*11:01 allele was indicative of a worse OS, DFS and a higher rate of TRM. The associations of HLA and HSCT clinical outcome parameters found in this study justify further investigation of this matter., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study retrospectively investigated the association between the level of human leukocyte antigen (HLA) mismatches (MMs), direction of disparities and differences at particular HLA locus on clinical outcomes of hematopoietic stem cell transplantation (HSCT). Investigated outcomes were overall survival (OS) and disease-free survival (DFS), graft-versus-host disease (GvHD), relapse and non-relapse mortality (NRM)., Patients and Methods: Study cohort included 108 adult patients transplanted between 2011 and 2021 and their 9/10 mismatched unrelated donors (MMUD). All individuals were typed for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci using Polymerase Chain Reaction-Sequence Specific Primers, PCR-Sequence Based Typing and Next-Generation Sequencing. All statistical analyses were done in the MedCalc software, version 19.2.6., Results: Patients with MMs at HLA-B locus demonstrated worse OS (P ​= ​0.0440, HR ​= ​2.00, n ​= ​20). Absence of HLA-DRB5 was associated with a higher incidence of GvHD (P ​= ​0.0112, HR ​= ​1.93, n ​= ​67). A lower incidence of GvHD was observed in patients with HLA class II MMs compared to patients with HLA class I MMs (P ​= ​0.0166, HR ​= ​1.94, n ​= ​29). Finally, analysis of PIRCHE score (PS) impact revealed that patients with HLA class II PS ​> ​10 in GvH direction showed higher incidence of GvHD compared to patients with HLA class II PS ​< ​10 (P ​= ​0.0073, HR ​= ​2.01, n ​= ​55)., Conclusion: Obtained results undisputedly indicate the necessity to further investigate this matter on a larger patient group, with focus on specific HLA alleles to define precisely priority criteria for selecting the best donor for all patients, thus improving the outcome of HSCT with an MMUD., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2023 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant or non-malignant hematologic diseases from three Croatian treatment centers. An electrochemiluminescent assay was used to measure total anti-SARS-CoV-2 S-RBD antibody titers. After one vaccine dose, 20/66 (33%) achieved seropositivity with a median antibody titer of 6.1 U/mL. The response rate (58/90, 64.4%) and median antibody titer (>250 U/mL) were higher after two doses. Seropositivity varied with diagnosis (overall p < 0.001), with the lowest rates in lymphoma (34.6%) and chronic lymphocytic leukemia (52.5%). The overall response rate in chronic myeloproliferative neoplasms (CMPN) was 81.3% but reached 100% in chronic myeloid leukemia and other non-myelofibrosis CMPN. At univariable analysis, age > 67 years, non-Hodgkin’s lymphoma, active treatment, and anti-CD20 monoclonal antibody therapy increased the likelihood of no vaccine response, while hematopoietic stem cell recipients were more likely to respond. Age and anti-CD20 monoclonal antibody therapy remained associated with no response in a multivariable model. Patients with the hematologic disease have attenuated responses to SARS-CoV-2 vaccines, and significant variations in different disease subgroups warrant an individualized approach.

Introduction: We investigated the association of HLA on clinical outcomes in our cohort of patients in the haplo-HSCT program using the HLAMatchmaker (EM) and PIRCHE score (PS) algorithms., Methods: The group comprised 64 patients (male = 35-54.7%, female 29-45.3%; median age 43 years) and their related haplo-HSCT donors (male = 30-46.9%, female 34-53.1%). HLA-A/B/C/DRB1/DQB1/DPB1 loci were analyzed., Results: Multivariate analysis of the association between different HLA or patient/donor-related parameters and clinical outcome revealed the following associations with statistical significance: GvHD and HLA class I PS in the GvH direction (p = .0420) and relapse with diagnosis (p = .0163). For OS, the only variable showing a tendency of association was the source of HSCT (p = .0965)., Conclusion: Combined results of univariate and multivariate analysis suggest that the patients awaiting the selection of the best haplo-HSCT donor could benefit the most from the combination of all three approaches, in cases when a suitable donor can be chosen from a number of potential donors., (© 2022 John Wiley & Sons Ltd.)

Aim: To assess the correlations of B regulatory cells (Bregs) and monocyte subsets in peripheral blood with the National Institutes of Health (NIH)-consensus-defined clinical manifestations of chronic graft-vs-host disease (cGvHD), in an attempt to establish their role as cellular biomarkers., Methods: This multidisciplinary prospective study enrolled adult cGVHD patients treated in the University Hospital Center Zagreb and University of Zagreb School of Medicine. Immunophenotypic subpopulations of CD24highCD38high Bregs (CD27-, CD27+, and total) and monocyte (classical, intermediate, and non-classical) counts were correlated with demographic, transplant, and cGVHD-related data. Bivariate correlation analysis was performed to evaluate the correlations between Bregs and monocytes subsets and cGVHD organ involvement, as well as cGVHD severity and immunosuppression intensity., Results: Twenty-two adult patients (54.5% female) with cGVHD were enrolled. The median (range) age was 44.5 years (24-65). All patients were transplanted for hematologic malignancies and 40.9% had severe NIH cGVHD global score. The median time from cGVHD diagnosis to the analysis was 16.6 months (0-176). The organ most frequently affected with cGVHD were the eyes (68.2%), skin (45.5%), lungs (45.5%), and liver (40.9%). Lower total and CD27-Bregs counts were correlated with worse cGVHD severity, higher immunosuppression intensity, and lung cGVHD, in terms of cell count, but also with skin cGVHD, in terms of percentages. Patients with liver and joint/fascia cGVHD had a lower percentage of non-classical monocytes and patients with more severe global NIH score had a higher classical monocytes count., Conclusion: Different organs affected by cGVHD are differently associated with different subpopulations of Bregs and monocytes.

Purpose: This study investigated the frequency and characteristics of sarcopenia among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a specific focus on the chronic graft-versus-host disease (cGVHD) population and its association with malnutrition, vitamin D and clinical characteristics., Methods: We assessed sarcopenia, vitamin D levels, and nutritional status in 73 patients who underwent allo-HSCT, of which 45 were diagnosed with cGVHD. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria., Results: Sarcopenia was diagnosed in 19.2% of patients after allo-HSCT with statistically no significant difference between cGVHD and non-cGVHD patients. The risk factor for sarcopenia was the male gender. Sarcopenia in allo-HSCT patients correlated strongly with malnutrition and with current corticosteroid treatment (p < 0.005). Among cGVHD patients sarcopenia additionally correlated strongly with the number of prior systemic immunosuppressive therapy lines (p < 0.005) and moderately with the intensity of immunosuppression, cGVHD severity global rating assessed by both the health care provider and the patient and joint and fascia cGVHD involvement (p < 0.05). Vitamin D deficiency was found in more than 54.8% of patients, but the correlation to sarcopenia was not found., Conclusion: Sarcopenia was found to be common in long term survivors of allo-HSCT independently of the cGVHD diagnosis. Prospective longitudinal studies are needed for a better understanding of factors affecting the development of sarcopenia after allo-HSCT.

Matching for HLA-A, -B, -C, -DRB1, -DQB1 alleles is the gold standard in hematopoietic stem cell transplantation (HSCT). However, this is often not enough to prevent postransplantational complications. The HLA mismatches (MM) have been associated with higher risk of acute graft versus host disease (GvHD). Gamma block (GB) is located in central HLA region, between HLA-B/C and HLA-DRB/DQB blocks and contains many inflammatory and immune regulatory genes. Single nucleotide polymorphisms (SNPs) within that block can be considered as markers for MHC haplotype matching. Aim of the research was to test whether MM in GB impact the outcome of HSCT in 51 patients transplanted with HLA 10/10 matched unrelated donor. The recipient-donor pairs were typed using PCR SSP kit that detects 25 SNPs within GB. Fifteen out of 51 (29.41%) pairs were GT matched (GT-M) while 36 out of 51 pairs (70.59%) were mismatched (GT-MM). In a univariate analysis, GT-MM was a significant risk factor associated with aGvHD (P = 0.041), although this association was not seen in multivariate analysis. No significant difference in overall survival and relapse occurrence was seen. These results were obtained on a small sample, and it is necessary to further test the possible role of GT matching in unrelated HSCT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Chimerism status evaluation is a routine test performed in post-hematopoietic stem cell transplantation (HSCT) period. The aim of the study was to evaluate a quantitative polymerase chain reaction (qPCR) method (GenDx, Utrecht, the Netherlands) applicability for this purpose. The study included 74 recipient/donor pairs tested for informative markers: median of four and six informative markers was found for patients (related and unrelated donor, respectively). Higher sensitivity of qPCR method was confirmed by analysis of recipient post-HSCT samples (N = 800) among which microchimerism (0.1%-1% recipient DNA) was detected in 21.8% of cases. The ability to detect less than 1% of minor population, as opposed to the short tandem repeat (STR) method for which 1% is the limit, translated into earlier identification of a disease relapse for four patients in our study sample., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Thrombosis is the most common complication in Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms patients., Patients and Methods: In a cohort of 258 Ph- myeloproliferative neoplasm patients, the difference between patients with and without thrombosis was analyzed according to genetic thrombophilia factors, JAK2 V617F status and burden allele, blood count, cardiovascular risk factors and age. Patients were also divided in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) subgroups as well as by the type of thrombosis., Results: Analysis of cardiovascular risk factors regarding arterial thrombosis showed that PV patients with thrombosis had higher incidence of diabetes (P = .030), ET patients more often had hypertension (P = .003) and hyperlipidemia (P = .005), while PMF patients had hyperlipidemia (P = .046) and at least one cardiovascular risk factor (P = .044). Moreover, leukocytes > 18 × 10 9 /L and V617F burden allele > 25.7% were statistically significantly different in PV patients (P = .019 and borderline significant at P = .055, respectively), while in ET patients leukocytes > 9.2 × 10 9 /L (P < .001) and age at diagnosis of > 55 years were statistically significantly different (P = .002). PMF patients with V617F burden allele ≤ 34.8% were more prone to thrombosis (P = .032). When comparing patients with and without venous thrombosis, cutoff value of V617F burden allele > 90.4% was significant for PV patients with thrombosis (P = .036), as was > 56.7% for PMF patients with thrombosis (P = .046). Platelets ≤ 536 × 10 9 /L and age at diagnosis > 54 years showed statistically significant difference for ET patients with thrombosis (P = .015 and P = .041, respectively)., Conclusion: On the basis of our results, a new scoring system for thrombosis risk in PV could be made, while PMF prognostic model may be expanded for better recognition of potential thrombotic risk factors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Conflicting results have been reported regarding the association between early cytomegalovirus (CMV) reactivation and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This prompted us to evaluate the impact of CMV reactivation on outcomes of 155 consecutive adult patients transplanted in our institution. In our study, CMV reactivation did not affect cumulative incidence (CI) of relapse in patients with lymphoproliferative disorders. However, the CI of relapse in patients with myeloproliferative disorders (AML and MPN) was 37% (95% CI, 21-53) in patients without CMV reactivation as opposed to 17% (95% CI, 9-28) in patients with CMV reactivation (p = 0.03). An important correlation between CMV reactivation and relapse was found in patients with MPN; the CI of relapse was 50% (95% CI, 12-80) in patients without CMV reactivation as opposed to only 7% (95% CI, 0-27) in patients with CMV reactivation (p = 0.02). A substantial reduction of relapse in myeloproliferative disorders associated with CMV reactivation was confirmed by multivariate analysis (HR 2.73; 95% CI, 1.09-6.82, p = 0.03) using time-dependent covariates for high-risk disease, older age, RIC conditioning, ATG, grade II-IV acute, and chronic GVHD. To our knowledge, we are the first to show an association of CMV reactivation with relapse reduction in MPN patients. This putative virus vs myeloproliferation effect warrants further research.

Background: Oral chronic graft-versus-host disease (cGvHD) impairs oral function and patients' quality of life. Some lesions are refractory to local and systemic immunosuppressive therapy, and new therapeutic modalities are required. The aim of the study was to assess the efficacy and safety of topical application of autologous platelet gel (PG) in patients with oral cGvHD., Study Design and Methods: PG was prepared from autologous blood and applied on ulcerous lesions using an automated system. The oral cGvHD was assessed using the 273-point Oral Mucositis Rating Scale (OMRS) prior and after completion of the PG treatment. The overall response to treatment of particular topography expressed as the total score on OMRS was compared to total score on National Institutes of Health cGvHD Oral Mucosal Score (NIH OMS). The pain intensity was measured by the Numeric Pain Rating Scale (NRS)., Results: In five patients, 12 autologous blood collections were performed; median 3 (range 1-3) per patient, and 26 PG applications were performed; median 6 (range 2-8) per patient. PG applications reduced lesions in oral cGvHD: median OMRS total score was reduced for 43.2% (range 9.6%-47.3%), and median NIH OMS total score for 27.3% (range 20.0%-50.0%) from baseline values. Median of pain intensity reduction on NRS scale was 57.1% (range 50%-100%). No side effects were observed., Conclusion: Application of autologous PG in oral cGvHD showed as an efficient and safe treatment option for patients who do not respond to standard local treatment., (© 2018 AABB.)

The impact of patient/donor matching for HLA-A, -B, -C, -DRB1 and -DQB1 genes in hematopoietic stem cell transplantation (HSCT) is well-recognized, but typing for additional genes, such as HLA-DPB1, is still controversial. Based on defined T-cell epitope (TCE) groups, all HLA-DPB1 mismatches can be classified as permissive or non-permissive. In this retrospective study we analysed 82 patient-matched unrelated donor (MUD) pairs who underwent HSCT, and explored the impact of HLA-DPB1 matches, permissive and non-permissive mismatches on transplantation outcomes. Patient-MUD pairs matched for HLA-DPB1 alleles in univariate analysis were associated with a significantly higher incidence of disease relapse compared to pairs who were permissive/non-permissive HLA-DPB1 mismatched according to the TCE3 and TCE4 algorithms (P=0.025 and P=0.026, respectively), although the significance was lost in multivariate analysis. The analysis did not reveal any significant influence of HLA-DPB1 alleles on overall survival (OS), non-relapse mortality (NRM) or graft-versus-host disease (GvHD) incidence. In conclusion, our study presents evidence that HLA-DPB1 matching influenced the relapse rate in patients after HSCT so the HLA-DPB1 alleles should be implemented in the MUD search algorithm as a transplantation determinant., (Copyright © 2017. Published by Elsevier Inc.)

Killer cell immunoglobulin-like receptors (KIR) are a family of inhibitory/activating receptors expressed on NK cells. Interactions of KIR receptors with KIR ligands have been shown to modify hematopoietic stem cell transplantation (HSCT) outcome. The aim of this research was to determine the KIR2DS4 allele variants distribution among 111 patients with different hematological malignancy who underwent HSCT and their donors, and to evaluate KIR2DS4 alleles' impact on HSCT outcome. The KIR gene frequency analysis showed a significantly higher incidence of full-length KIR2DS4 alleles among patients. The impact of KIR2DS4 alleles on transplantation outcomes revealed that donors' full-length KIR2DS4 alleles is associated with lower overall survival rates, higher risk of GVHD and higher relapse incidence. The expression of full-length KIR2DS4 allele variants may contribute to a worse clinical outcome after HSCT. KIR typing for KIR2DS4 could be used as an additional criterion for selecting suitable donors in cases when more than one HLA identical donor is identified for a specific patient., (Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

The knowledge of HLA characteristics of a patient's population helps to predict the probability of finding a MUD. The study included 170 transplanted patients for whom a search for a MUD in BMDW was performed and a sample of 4000 volunteer unrelated donors from the Croatian Bone Marrow Donor Registry (CBMDR). Patients and their MUDs were typed for HLA-A, -B, -C, -DRB1, and -DQB1 loci using PCR-SSO and PCR-SSP methods while donors were typed for HLA-A, -B, -C, and -DRB1 loci using the PCR-SSO method. A comparison of allele frequencies at tested HLA loci between patients and donors from CBMDR did not reveal significant differences. The majority of patients (117, 68.8%) had a 10/10 MUD, 45 (26.5%) patients had a 9/10 MUD and eight (4.7%) patients had an 8/10 MUD. The highest number of mismatches (MM) was present at HLA-DRB1 (19; 31.1%). The presence of DRB1*11 and DRB1*04 allelic groups among patients caused allelic MMs at HLA-DRB1 in most cases. The presence of an infrequent HLA-B∼C haplotype resulted in the HLA-C MM at antigen level in the majority of cases. The present study clarified HLA factors that cause difficulties in searching for a 10/10 MUD for Croatian patients., (Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Introduction: For over a decade, imatinib has been the first-line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML). Doubts on the bioequivalence and bioavailability of emerging generic compounds have been expressed. Adequate imatinib plasma concentration ([IPC] ≥1000 μmol/L) is associated with a better chance of optimal treatment response in patients with CML. In this study, we compared the achieved IPCs between the branded compound and its 2 generic forms., Patients and Methods: IPCs were compared in 24 consecutive patients with CML in the first chronic phase who changed from branded to generic imatinib. The median age was 49 years (range, 22-76 years). Fifteen of them were male. Six patients were switched to Neopax, 13 to Imakrebin, and 5 patients received both generics consecutively. All compounds were used in an equivalent dose of 400 mg orally once daily for at least 1 month before plasma concentrations were measured. High-performance liquid chromatography was used to determine imatinib plasma concentration from a specimen collected 21 to 24 hours after the last dose., Results: The median IPC achieved with branded imatinib was 1454 μmol/L (range, 485-2707 μmol/L) with 18 patients (75%) having IPC ≥ 1000 μmol/L. For Neopax and Imakrebin, median IPCs were 1717 μmol/L (range, 1249-3630 μmol/L) and 1458 μmol/L (range, 707-880 μmol/L), respectively, with 11 of 11 (100%) and 16 of 18 (89%) patients having IPC ≥ 1000 μmol/L. No significant difference in measured IPCs between all 3 compounds was found (P > .257)., Conclusion: When taken at equivalent doses, imatinib generics are bioequivalent and comparable in clinical efficacy and have the potential for substantial savings in the treatment cost for CML., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To determine the frequency and the characteristics of cutaneous manifestations, especially vitiligo and alopecia areata, in patients with chronic graft-vs-host disease (cGVHD)., Methods: 50 patients with cGVHD were prospectively enrolled in the observational study protocol and evaluated by an experienced dermatologist. The evaluation was focused on the clinical spectrum of skin and adnexal involvement, and the cutaneous GVHD score was determined according to National Institutes of Health (NIH) Consensus criteria. The presence of vitiligo, alopecia, xerosis, nail changes, and dyspigmentation was also assessed., Results: Out of 50 cGVHD patients, 28 (56%) had skin involvement, and 27 of them (96%) had hypo and/or hyperpigmentations. 11 patients (39%) had a mild cutaneous NIH cGVHD score, 22% moderate, and 39% severe. 15 (30%) patients had nail changes and 10 (20%) had vitiligo or alopecia areata. Univariate analysis showed that patients with vitiligo/alopecia areata received more lines of prior systemic immunosuppressive therapy (P=0.043), had lower Karnofsky performance status (P=0.028), and had a higher B-cell number (P=0.005), platelet count (P=0.022), and total protein (P=0.024). Vitiligo and alopecia areata were associated with higher NIH skin score (P=0.001), higher intensity of immunosuppressive treatment (P=0.020), and total body irradiation conditioning (P=0.040). Multivariate regression model showed that patients with higher NIH skin scoring were 3.67 times more likely to have alopecia and/or vitiligo (odds ratio 3.67; 95% confidence interval 1.26-10.73), controlled for all other factors in the model (age at study entry, number of B-cells, platelet count, and global NIH score)., Conclusion: These data indicate that vitiligo and alopecia areata occur more frequently in cGVHD than previously reported.

Aim: To investigate the ability of two standard quality of life (QOL) questionnaires - The Short Form (36-item) Health Survey (SF-36) and The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ C30) to evaluate QOL in patients with chronic graft-vs-host disease (cGVHD) graded according to National Institutes of Health (NIH) consensus criteria., Methods: In this cross-sectional study, QOL was assessed in patients who underwent allogeneic stem cell transplantation (allo-SCT) at the University Hospital Centre Zagreb and were alive and in complete remission for more than one year after allo-SCT., Results: The study included 58 patients, 38 patients with cGVHD and 20 controls, patients without cGVHD. Patients with cGVHD scored according to the NIH criteria had significantly lower scores of global health status and lower QOL on all SF-36 subscales and most of QLQ C30 functional subscales (P<0.050 for all comparisons). Furthermore, patients with active cGVHD had significantly lower QOL scores than patients with inactive cGVHD, and this difference was most evident in physical functioning subscale of SF-36 (P=0.0007) and social functioning subscale of QLQ C30 (P=0.009)., Conclusion: cGVHD scored according to the NIH criteria is correlated with patient-reported QOL, particularly in the physical domains as detected by SF-36. QLQ C30 questionnaire adds more information on social functioning and should be used as a valuable tool in the evaluation of social domains in cGVHD patients.

The aim of the present study was to investigate HLA alleles and haplotypes among Croatian patients in an unrelated HSCT program, and to analyze HLA matching in patient/donor pairs. Analysis was performed on a group of 105 patients and their donors, and 4000 unrelated donors from our registry (CBMDR) served as controls. PCR-SSO and PCR-SSP high-resolution methods for HLA-A, -B, -C, -DRB1, and -DQB1 loci were used for typing patient/donor pairs. Donors from CBMDR were tested for HLA-A, -B, and -DRB1 by PCR-SSO. No difference in frequency at HLA tested loci among patients and donors from CBMDR was observed. A fully matched donor (10/10) was found for 68 (64.8%) patients, and the highest number of mismatches was found for HLA-DRB1 and HLA-C alleles. The presence of HLA-B alleles (B*15:01, B*18:01, and B*51:01) associated with two or more HLA-C alleles as well as the presence of unusual HLA-B/HLA-C (B*35:01-C*07:01 and B*35:01-C*14:02) combinations resulted in mismatches at the HLA-C locus. Additionally, mismatches at the DRB1 locus were in most cases found for DRB1*11 alleles. The results suggest that the DRB1*11:04 allele might be considered as a limiting factor in finding a 10/10 matched donor. These data may help in the improvement of the searching protocol for unrelated donors for Croatian patients., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aim: To investigate the influence of tumor necrosis factor (TNF) microsatellite polymorphisms on patient survival following hematopoietic stem cell transplantation., Methods: We analyzed TNFa, TNFb, and TNFd microsatellites among 100 patients who underwent allogeneic hematopoietic stem cell transplantation from a human leukocyte antigen (HLA)-identical sibling donor at the Internal Clinic of the University Hospital Center Zagreb in the period 2001-2009. The analysis was performed using polymerase chain reaction amplification and electrophoresis on a polyacrylamide gel in an automated sequencer., Results: There was no significant difference in patient survival with respect to the allele length at a given microsatellite. However, a significantly lower survival rate was noticed among patients who were positive for TNFa8 allele (P<0.001) and a significantly higher survival rate among those who were positive for TNFa10 allele (P=0.0220)., Conclusion: These results for the first time suggest an influence of TNFa microsatellite on patient survival following HSCT and indicate a need for further studies of this microsatellite.

Objective: A rise in infections with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is a significant contributor to increased morbidity and mortality of patients with hematologic malignancies. The aim of this study was to determine the efficacy and safety of colistin (colistimethate sodium) in the treatment of serious infections caused by MDR-PA in these patients., Patients and Methods: A matched pair analysis of renal function, toxicities, and outcome of 26 patients receiving colistin and control subjects was done. All patients had clinical signs of sepsis; P. aeruginosa was isolated from blood in 69% of patients in colistin group and 84% in control group. Patients treated with colistin received 3 million units every 8 hours for a median duration of 13 days. Additionally, patients received at least two additional antimicrobial or antifungal drugs., Results: Resolution of infection was achieved in twenty patients (76.9%) receiving colistin and in 17 (65.4%) control subjects. Mortality rate was 11% in both groups. There was no statistically significant difference in the level of serum creatinine, creatinine clearance, or potassium levels before and after treatment between groups. Only one patient receiving colistin developed de novo renal failure and one displayed transient neurologic toxicity., Conclusion: Our results suggest that in patients with hematologic malignancies, colistin is effective in treating severe infections caused by MDR-PA while maintaining an acceptable toxicity profile. Prospective randomized studies comparing efficacy and safety of colistin with those of other antipseudomonal drugs are needed.

Hematopoietic stem cell (HSC) transplantation is a standard approach in the treatment of hematological malignant diseases. For the last 15 years the main source of cells for transplantation have been peripheral blood stem cells (PBSC). With the availability of hematopoietic growth factors and understanding the advantages of treatment with PBSC, the application of bone marrow (BM) was supplanted. The aim of this survey was to explore the success of PBSC collection, the factors which influence the success of PBSC collection, the composition and the quality of graft and their influence on hematopoietic recovery and outcome after transplantation in patients with acute myeloid leukemia (AML). PBSC were collected by the method of leukapheresis after applying a combination of chemotherapy and growth factors or only growth factors. The quality of graft was determined with the clonogenic progenitor cell assay and with the flow cytometry analysis. Of the total 134 patients with AML, who were submitted to HSC mobilization, the collection was successful in 78 (58.2%) patients. The collection was more successful after the first than after the second attempt of HSC mobilization (49% vs. 11%). The criteria for effective mobilization were the number of leukocytes > 3 x 10(9)/L and the concentration of CD34+ cells > 20 x 10(3)/mL in the peripheral blood on the first day of leukapheresis. The number of CD34+ cells infused had the strongest impact on hematopoietic recovery. We noted significantly faster hematological recovery of neutrophils and platelets, fewer number of transfused units of red blood cells and platelets, shorter duration of the tranfusion support, shorter treatment with intravenous antibiotic therapy and shorter hospitalization after PBSC compared to BM transplantation. These advantages could provide their standard application in the treatment of patients with AML.