Blastic plasmacytoid dendritic cell neoplasm: First retrospective study in the Czech Republic.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with aggressive behavior and poor prognosis. We present the first retrospective analysis mapping its incidence and therapeutic outcomes in patients diagnosed and treated from 2000 to 2017 in the Czech Republic. The cohort comprised 14 patients (10 males, 4 females) with a median age at diagnosis of 39 years (range, 5-68 years). Initially, skin involvement was noted in 10 (71%) patients and bone marrow infiltration was present in 9 (64%). The first complete remission was achieved in 6/14 (43%) patients after acute lymphoblastic leukemia/lymphoma induction therapy and in 3/14 (21%) patients after acute myeloid leukemia regimen. Nine patients underwent allogeneic hematopoietic cell transplantation, with two patients achieving the first complete remission only after allogeneic transplantation. Patients undergoing allogeneic hematopoietic cell transplantation had longer overall survival than those treated without transplantation (the median survival over the period 16.4 vs. 8.1 months). Relapse of the disease was a significant predictor of mortality (p=0.05). Over the study period, patients' survival ranged from 3.3 to 44.2 months, with a median overall survival of 13 months. Our results revealed an effectivity of allogeneic hematopoietic cell transplantation on complete remission achievement in refractory/relapsed disease. The study aimed to present the actual data from the Czech Republic and thus contribute to a global understanding of BPDCN.

Comparison of the immunomodulatory effect of single MSC batches versus pooled MSC products.

Severe corticosteroid-refractory graft-versus-host-disease (GVHD) is a major non-relapse cause of mortality and morbidity after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). One of the most promising treatment options is using advanced therapy medicinal products based on mesenchymal stem cells (MSCs) immunomodulation ability. The protocols of MSC application differ in many parameters including a source of MSC, a dose, a number of doses or way of preparation of the medicinal product. The process is limited by the need for laborious and expensive manufacturing processes fraught with batch-to-batch variability. In our study, we compared the immunomodulatory effects of different MSC batches versus pooled MSC, specifically the influence on lymphocyte proliferation, the metabolic activity, and the expression of activation markers on T cells. Our goal was to determine whether the effect depends on donor-to-donor heterogeneity and if pooling of MSCs could increase their immunomodulatory ability. All tested batches showed an immunomodulatory effect, with no significant differences between the groups. Our study suggests that immunosuppressive potential is comparable in single batches and pooled products, and the use of products got from individual donors is suitable to treat corticosteroid-refractory GVHD.

Development of Resistant GvHD in a Patient Treated with Nivolumab for Hodgkins Lymphoma Relapse after Allogeneic Unrelated Transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation is one of the therapeutic options for patients with relapsed or refractory classic Hodgkins lymphoma (cHL). In the case of dis-ease relapse after transplant, other treatment options are still limited (for example donor lymphocyte infusion, and chemother-apy with brentuximab, bendamustine, or other agents) with uncertain outcomes in terms of patient tolerance and long-term dis-ease remission. One way to achieve remission is administration of the PD-1 inhibitor nivolumab, a PD-1 checkpoint inhibitor. Nivolumab is also indicated for the treatment of cHL relapses after autologous hematopoietic stem cell transplantation. Since September 2018, nivolumab has been approved by the State Institute for Drug Control in the Czech Republic for treatment of cHL autologous hematopoietic stem cell transplantation relapse; however, treatment with nivolumab is accompanied by an increased risk of develop-ing fatal, acute graft-versus-host dis-ease. CASE: The article describes the development of resistant acute graft-versus-host disease in a patient who had received allogeneic-unrelated transplantation and nivolumab treatment for Hodgkins lymphoma relapse. CONCLUSION: Our case study, as well as the literature review, demonstrates the excellent efficacy of PD-1 inhibitors, but also cautions against the administration of these agents in patients follow-ing allogeneic hematopoietic stem cell transplantation. Administration of nivolumab to these patients should be done on a strictly individual basis in the context of known risks, and consideration should be given to other treatment options. Key words Hodgkins lymphoma -  PD-1 inhibitor -  nivolumab -  GvHD -  transplantation.

Comparison of autologous hematopoietic cell transplantation performed in tandem and in disease relapse in multiple myeloma patients.

Multiple myeloma is a malignant hemato-oncological malignancy that affects up to 600 people in the Czech Republic every year. Treatment options are under constant improvement and the autologous hematopoietic cell transplantation (Tx) remains a part of treatment protocols. Despite modern drug administration, the autologous Tx keeps its irreplaceable position and when ensuring two autologous Tx, the studies confirm a survival time more than twice as long as in non-transplant patients. However, there are no standardized procedures specifying the period in between the transplantations in more detail. Within our group, we compared the total of 66 patients who were administered a double transplant. One group underwent both planned tandem autologous Tx within a median of six months and mostly achieved just partial remission (PR) and less after the first transplant and out of disease progression. The other group only underwent the second Tx within a median of up to 14 months during a progression period or disease relapse. Both groups were comparable as far as basic parameters are concerned (age, type of induction therapy and cytogenetic risk). A significantly better treatment free survival (TFX) and overall survival (OS) were observed in the group where tandem Tx was administered. TFS was 18 months and median OS was not reached for the group of patients who received tandem Tx, while TFS was 10 months (p=0.04) and median OS was 57 months (p=0.005) for those who received delayed second Tx. In the group of patients who received second Tx during relapse, we observed that TFS and OS were shorter in those with a higher paraprotein level, thus suggesting the potential role of paraprotein level as a prognostic marker. The TFS in the subgroup with a high initial level was 4 months vs. 11 months (p=0.0016) and OS 44 months vs. 65 months (p=0.03).

Association of HLA-DRB1 and HLA-DQB1 with red-blood-cell alloimmunization in the Czech population.

BACKGROUND AND OBJECTIVES: Alloimmune antibodies against red-blood-cell (RBC) antigens induced in susceptible individuals (responders) by transfusion, pregnancy or transplantation may have serious clinical consequences. The aim of this study was to investigate association of alloimmunization against selected RBC antigens with HLA-Class II. MATERIALS AND METHODS: A total of 230 responders (106 monoresponders and 124 multiresponders) were enrolled into the study. HLA-DRB1 and HLA-DQB1 variants were determined by PCR-SSO and their frequencies compared between the patients (patient subgroups) and 375 ethnically and regionally matched controls. RESULTS: Development of multiple RBC antibodies was associated with HLA-DRB1*15 and HLA-DQB1*06 allelic groups in the patients, with the relationship being particularly apparent in those with anti-C+D antibodies. Furthermore, DRB1*13 and DQB1*06 were more frequent in multiresponders with anti-E+c antibodies and DRB1*03 and DQB1*02 in those with anti-E+Cw. CONCLUSION: For the first time, we confirmed the association of HLA-DRB1*15 with RBC antibody multiresponder status and found HLA-Class II associations for three frequent RBC antibody combinations. Our data support the concept that HLA restriction plays an important role in the response to RBC alloantigens.

Prognostic factors to predict outcome of reduced intensity allogeneic haematopoietic cell transplantation for chronic lymphocytic leukemia.

Despite advances in immunochemotherapy CLL remains an incurable disease.. Allogeneic haematopoietic cell transplantation (HCT) has proven curative potential with ability to overcome adverse prognostic factors, however due to its toxicity it is generally perceived as the last option. We performed retrospective study to explore the outcomes and possible determinants of survival in the unselected consecutive cohort of 68 CLL patients (median age 59 years) receiving reduced intensity HCT as a part of salvage therapy in 2 Czech centers. The median interval from diagnosis to HCT was 69 months with median 3 of prior regimens, all patients were refractory to purine analogues. 49% of patients were transplanted with advanced (i.e. refractory or progressive disease or CR/PR>3), 38% had high risk cytogenetics. With median follow-up of 35 months the 3-year Kaplan-Meier survival probability for OS and PFS were 39% and 26%, respectively. Altogether 18 patients (26%) have relapsed or progressed. During the follow-up 41 patients died, 32 (78%) of transplant related factors (NRM), the others of relapse or disease progression.Univariate analysis failed to identify any clinical and pre- or post-transplant variables having clear prognostic significance for OS or PFS. The marginal OS advantage favoring HCT performed recently was detected (3-year OS: 31% for HCT until 2006 and 47% thereafter, p=0.0923). In multivariable hazards model only the female donors were associated with shorter OS (HR 2.278, p=0.016) whereas transplanted T-cell> 2.75x108/kg predicted inferior PFS(HR 1.957, p=0.035). No prognostic impact of donor type, age of donor and recipient, HLA mismatch, disease status pre-HCT, number of previous therapy lines, interval from dg. to HCT and number of transplanted hematopoietic cells was found. Our findings support the conclusion that alloHCT is able to overcome well known negative cytogenetic prognostic factors and that preferring male to female donors could be beneficial.

The Quality Control of Mesenchymal Stromal Cells by in Vitro Testing of Their Immunomodulatory Effect on Allogeneic Lymphocytes.

Mesenchymal stromal cells (MSC) represent a promising treatment of graft-versus-host disease (GVHD) in patients after allogeneic haematopoietic stem cell transplantation. We performed co-cultivation experiments with non-specifically stimulated lymphocytes to characterize the immunosuppressive activity of MSC. MSC influenced expression of some activation antigens. CD25 expression was lower with MSC and reached 55.2 % vs. 84.9 % (CD4+, P = 0.0006) and 38.8 % vs. 86.6 % (CD8+, P = 0.0003) on day +4. Conversely, CD69 antigen expression remained higher with MSC (73.3 % vs. 56.8 %, P = 0.0009; 59.5 % vs. 49.7 %, ns) and its down-regulation along with the culture time was less pronounced. MSC reduced proliferation of the stimulated lymphocytes. The cell percentages detected in daughter generations were decreased (32.82 % vs. 10.68 % in generation 4, P = 0.0004 and 29.85 % vs. 10.09 % in generation 5, P = 0.0008), resulting in a lower proliferation index with MSC (1.84 vs. 3.65, P < 0.0001). The addition of MSC affected expression of some cytokines. Production of pro-inflammatory cytokines was decreased: IL-6 (19.5 vs. 16.3 MFI; P < 0.0001 in CD3+/CD4+ and 14.5 vs. 13.2 MFI; P = 0.0128 in CD3+/CD8+), IFN-γ (13.5 vs. 12.0 MFI; P = 0.0096 in CD3+/CD4+). Expression of anti-inflammatory IL-10 was only slightly increased after the addition of MSC (ns). The analysis confirmed the immunomodulatory activity of MSC. The functional tests have proved to be an important part of the quality control of the advanced therapy cellular product intended for GVHD treatment. Future research should focus on the interaction between MSC and the patient immune environment more closely.

[Radiotherapy Indications in Patients with Hematological Malignancies During the Five Years Course of Modernized Center of Oncology and Radiotherapy Clinic in Pilsen]. / Indikace radioterapie u pacientu s hematologickými malignitami v prubehu peti let provozu modernizovaného centra Onkologické a radioterapeutické kliniky v Plzni.

Submitted: 27. 2. 2016.

Sequential vs myeloablative vs reduced intensity conditioning for patients with myelodysplastic syndromes with an excess of blasts at time of allogeneic haematopoietic cell transplantation: a retrospective study by the chronic malignancies working party of the EBMT.

The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.

Tolerance to MHC class II disparate allografts through genetic modification of bone marrow.

Induction of molecular chimerism through genetic modification of bone marrow is a powerful tool for the induction of tolerance. Here, we demonstrate for the first time that expression of an allogeneic MHC class II gene in autologous bone marrow cells, resulting in a state of molecular chimerism, induces tolerance to MHC class II mismatched skin grafts, a stringent test of transplant tolerance. Reconstitution of recipients with syngeneic bone marrow transduced with retrovirus encoding H-2I-A(b) (I-A(b)) resulted the long-term expression of the retroviral gene product on the surface of MHC class II-expressing bone marrow-derived cell types. Mechanistically, tolerance was maintained by the presence of regulatory T cells, which prevented proliferation and cytokine production by alloreactive host T cells. Thus, the introduction of MHC class II genes into bone marrow-derived cells through genetic engineering results in tolerance. These results have the potential to extend the clinical applicability of molecular chimerism for tolerance induction.

A novel HLA-A null allele (A*02:395N) with stop codon in exon 2 generated by single nucleotide exchange.

The new HLA-A*02:395N allele differs from A*02:01:01 at one nucleotide position in the exon 2.

The outcome of allogeneic HSCT in older AML patients is determined by disease biology and not by the donor type: an analysis of 96 allografted AML patients ≥ 50 years from the Czech acute leukaemia clinical register (alert).

Older patients with AML have poor prognosis after chemotherapy and allo-SCT was historically limited to the young patients. In the multicentre retrospective study we analyzed 96 consecutive AML patients ≥ 50 years allografted with related (n=59) or unrelated (n=37) donor. The 2- year OS and DFS rates were 45 % and 42 % for the whole group. The corresponding figures for related patients were 48% and 42% whereas for unrelated 42% and 42%, respectively (OS p=0,721, DFS p= 0,896). The cumulative incidences of relapse (28% of all patients) and NRM mortality (26%) were low with no significant differences among related and unrelated cohorts. Multivariate analysis revealed the only major independent variables associated with an inferior OS were unfavourable cytogenetics (RR 3.36; CI 1.66-6.83; p=0.001) and advanced disease status (RR 2.30; CI 1.21-4.37; p=0.011). Unfavourable cytogenetics (RR 3.00; CI 1.50-5.99; p=0.002) and advanced disease at SCT (RR 2.27; CI 1.22-4.22; p=0.009) were also the only independent variables associated with inferior DFS. In conclusion, our analysis indicates that outcomes of allografted AML patients aged ≥ 50 years are determined by cytogenetic risk category and disease status at transplantation and not by the type of donor.

[Ultra high risk chronic lymphocytic leukemia -  characteristics and treatment options]. / Vysoce riziková chronická lymfocytární leukemie -  charakteristika a lécebné moznosti.

Chronic lymphocytic leukemia (CLL) is the most common form adult leukemia in western world. The disease is typically cha-racterized by heterogeneous clinical behavior ranging from indolent course to rapidly progressive disease. Using clinical and bio-logical factors we can stratify patients with CLL and prospectively identify those who can be expected unfavorable course. There is a special group known as ultra highrisk chronic lymphocytic leukemia with an extremely poor prognosis. These are about 10- 15% of all patients with CLL. They do not respond to standard treatment and their survival is short with a median of 2- 3 years. For highrisk patients are considered: patients with a proven TP53 defect, refractory to purine analogues or with early relapse after chemoimmunotherapy based on fludarabine ( 24 months). While the standard 1st line treatment protocol in younger patients is chemoimmunotherapy FCR, in case of ultra highrisk CLL other methods like allogeneic hematopoietic stem cell transplantation or clinical trials testing the new drugs should be considered. In particular, allogeneic hematopoietic stem cell transplantation is a very promising treatment modality that offers longterm disease control and cure regardless of the unfavorable CLL subtype. Transplantation treatment should be therefore considered in all younger patients with ultra highrisk CLL, who should be without delay referred to a center for intensive hematological treatment.

[The clinical, histopathological and imaging methods characteristics of Non-Hodgkin lymphomas in patients with brain involvement]. / Klinické, histopatologické a zobrazovací charakteristiky nonhodgkinských lymfomu u pacientu s postizením mozku.

BACKGROUND: The Non- Hodgkin-lymphoma (NHL) brain infiltration carries a poor prognosis. Because of relatively rare incidence, we decided to share our experience. PATIENTS AND METHODS: Retrospective analysis of patients with NHL brain infiltration dia-gnosed in 2001- 2011 at our university hospital. RESULTS: Twenty -seven patients with median age of 61 (range 42- 82) years were analyzed. The primary diffuse large cell B cell lymphoma of CNS was defined in 22/ 27 (81%) patients, in the others systemic NHL was present. Median positivity of the proliferative marker Ki 67 was 80%, the number of NHL lesions 1 (1- 8), diameter 28 × 30 × 29 (11 × 16 × 20 to 85 × 76 × 65) mm. The fundamental finding in brain lymphoma MRI imaging was lesion with predominantly homogenous contrast enhancement, diffusion restriction and collateral edema. Thirteen out of 27 (48%) patients underwent lumbar puncture, and lymphoma presence in fluid was detected in only two of them. The most frequent symptoms were limb paresis or hemiparesis (55%), bradypsichysm (22%), expressive aphasia (22%), cephalea (18%). Corticosteroid therapy, as a primary treatment option, was indicated in 15% of patients with a median overall survival of one month, CNS radiotherapy in 37% with a median survival of three months, and chemotherapy in 48% patients with a median overall survival 10 (2- 45) months. CONCLUSION: The brain lymphomas are rare and prognostically very unfavorable affection. When specifying brain focal lesions on MRI, it is necessary to consider this etiology and to elect imaging protocols with contrast agents and diffusion weighted sequence. Biopsy should be performed prior to start of corticosteroid therapy. Intensive chemotherapy or radiotherapy indication must be individually considered, and proposed treatment should be initiated immediately with a potential for somewhat prolonged survival.

[Spontaneous remission of acute myeloid leukemia - a single center case reports]. / Spontánní remise akutní myeloidní leukemie - klinické prípady jednoho centra.

BACKGROUND: Acute myeloid leukemia is a malignant disease characterized by clonal expansion of immature hematopoietic cells - myeloblasts - in the bone marrow. Intensive chemotherapy treatment in elderly patients (over 60) has disappointing results. In these patients, conservative treatment, including compensation of deficiency of red blood cells and platelets by transfusions and treatment of infectious complications is recommended. Also, relatively new treatment with hypometyl agents (azacytidine, decitabine) could be used. DESIGN: The idea of this article is to present a spontaneous remission phenomenon, which has not been published in Czech literature yet. In this article, we present 2 case studies of our patients who were diagnosed with acute myeloid leukemia, were not treated with chemotherapy and spontaneously reached remission of acute myeloid leukemia. CONCLUSION: The mechanisms of the spontaneous remission remain unclear, but we assume positive effect of a severe systemic infection or previous applications of blood transfusions. Antibodies in blood transfusions and a strong immune response to sepsis may have contributed to spontaneous remission.

CD34⁺ cell content in unrelated allogeneic peripheral blood stem cell grafts transported internationally. Does the inter-laboratory variability affect comparability of graft quality data?

BACKGROUND: Increasing numbers of unrelated hematopoietic stem cell grafts are transported internationally and evaluated concurrently in different laboratories. The graft quality assessment using the CD34(+) enumeration could be influenced by inter-laboratory variability. METHODS: We retrospectively analyzed the content of CD34(+) cells in 154 consecutive collections being performed in different transplant centers during two periods (2003-2004, 2007-2010). All samples were tested twice in our own and partner laboratories. CD34(+) percentage and absolute number were compared. RESULTS: The percentage and the total CD34(+) content correlated well in both observed periods (CD34(+)%: r=0.899 and r=0.922; CD34(+)×10(8)/kg: r=0.966 and r=0.880; p<0.0001). Median CD34(+) percentages obtained in our centre in comparison with other laboratories were 0.54% vs. 0.46% in 2003-2004 and 0.69% vs. 0.70% in 2007-2010 period. The degree of laboratory compliance was affected by the laboratory identity. CD34(+) percentage reported by one laboratory and CD34(+)×10(8)/kg reported by three from twelve laboratories lacked statistically significant correlation with our own data. CONCLUSIONS: The study documented that results of CD34(+) cell dose assessment of the same grafts reported by different transplant centers are comparable. The graft quality data and the CD34(+) enumeration possess a limited level of inter-laboratory variability.

[Angioimmunoblastic T-cell lymphoma as a very poor-prognosis malignancy--a single centre experience]. / Angioimunoblastický T-lymfom (AITL) jako velmi nepríznivá malignita - zkusenost centra.

BACKGROUND: Angioimmunoblastic T-lymphoma (AITL) is a poor prognosis malignancy. Because of relatively rare incidence and lack of publications in Czech, we decided to share our experience. PATIENTS AND METHODS: Retrospective analysis of newly diagnosed AITL patients treated at our institution between 1/2000-12/2010. RESULTS: Twelve patients with median age of 64 (43-82) years were analysed. Two patients over 80 years were treated with corticosteroids. Ten patients were treated with 6 cycles of CHOP-21 chemotherapy resulting in: 2/10 (20%) stable disease, 5/10 (50%) partial remission and 3/10 (30%) complete remission. The median EFS and OS of chemotherapy-treated patients were 8 and 10 months, resp. The EFS and OS were both significantly longer in patients who achieved complete remission within the first line of CHOP or autologous stem cells transplantation therapy: 43 vs 6 (p = 0.0052) and 46 vs 6 months (p = 0.0023), respectively. It was not possible to perform autologous transplantation in 4/7 (57%) patients in need for further reduction of the disease because of poor performance status or early progression of lymphoma and death during salvage chemotherapy. CONCLUSION: AITL is a poor prognosis malignancy with a very high risk of early relapse after CHOP induction chemotherapy. In fit patients, autologous transplantation should be performed immediately after induction chemotherapy; information about availability of stem cells donor, both in the family or any available register, should be found during the induction treatment.

[Patient with B-CLL with a history of unrelated hematopoietic cells donation--retrospective analysis of CLL development and implication for the recipient]. / Pacient s B-CLL s anamnézou darování krvetvorných bunek nepríbuznému pacientovi - retrospektivní sledování vývoje nemoci a dusledky pro príjemce.

BACKGROUND: Donor cell leukemia (DCL) is a relatively rare but well documented complication of hematopoietic stem cell transplantation. So far, publications described only DCL arising de novo in the recipient. OBSERVATION: In this study, we describe a case of chronic lymphocytic leukemia (B-CLL) developing in a volunteer unrelated donor from the Czech National Marrow Donors Registry (CNMDR) several years after donation. From archival DNA sample, we have retrospectively found that subclinical CLL clone was already present at the time of donation but early death of recipient prevented eventual development of DCL. This case documents well the long period between detection of B-CLL clone and full development of clinical-laboratory symptomatology. The medical and ethical questions posed by an isolated case of detection of hematological malignancy present either only in the donor or only in the recipient are discussed. CONCLUSION: The case demonstrates the increasing risk of development of various forms of DCL and thus highlights the need for long-term monitoring of stem cell donor, not only in terms of health of donor but also in terms of potential risks for the recipient.

[The incidence of malignancies and surveillance of hematopoietic stem cells donors--the results of the Haemato-Oncology Department University Hospital in Plzen (Pilsen) and Czech National Marrow Donors Registry observation]. / Výskyt malignit a dispenzarizace dárcu krvetvorných bunek--výsledky sledování Hematologicko-onkologického oddelení FN Plzen a Ceského národního registru dárcu drene

BACKGROUNDS: Granulopoesis colony-stimulating factor filgrastim is used to mobilize peripheral stem cells but there are concerns regarding an elevated risk of haematological malignancies. We analyzed the incidence of malignancies and the system of haematopoietic stem cells donor surveillance. PATIENTS AND METHODS: prospective observation of sibling donors of the Haemato-Oncology Department University Hospital in Plzen (Pilsen) and of unrelated donors of the Czech National Marrow Donors Registry (CNMDR) in 2001-2010. RESULTS: No malignancy was observed in a group of 344 unrelated CNMDR donors, providing 753 person-years; one case of chronic lymphocytic leukaemia manifested 6 years after bone marrow donation, with leukaemia clone retrospectively detected by DNA analysis in blood samples taken prior to the marrow donation. Acute myeloid leukaemia, non-Hodgkin lymphoma, renal and colorectal carcinoma were observed in a group of 84 peripheral stem cells sibling donors, providing 337 person-years observation. The respective incidence of the two haematologic malignancies was 593 cases and the expected incidence rate was 143 per 100,000. The sibling (related) donors age was significantly higher: 48 (16-75) vs. 31 (20-42) years, (p<0.0001). Significantly more lost-to-follow-up donors were among the related donors (32% vs. 3%, p<0.0001), even though active surveillance system was implemented. CONCLUSION: The development of malignancies in hematopoietic stem cells donors can naturally be expected. Related (sibling) donors are at higher risk because of their generally older age, and higher susceptibility to haematological malignancies developed within the family. The contribution of filgrastim exposure needs to be further investigated. The follow-up cooperation with related (sibling) donors is limited.

Detection of A B acute lymphoblastic leukaemia blast-specific mutation in HLA-B*39:01.

Human leucocyte antigen (HLA) modifications observed in blast cells in haematologic malignancies can play an important role in disease progression and its therapy. Here we describe an insertion/deletion mutation in the second exon of HLA-B*39:01 that occurred in the blast cells of a patient with B-ALL. This mutation was not present in the nonleukemic cells, in which HLA-B*39:01 was normally expressed.