Patrycja Zielinska

The Impact of H-Y Mismatches on Results of HLA-Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation

We searched for immunogenic mismatches of H-Y minor histocompatibility antigens among unrelated HLA-matched donor-recipient pairs and for their association with transplant outcomes. We included 92 patients who were treated with 10/10 HLA allele-matched, unrelated allogeneic hematopoietic stem cell transplantation (alloHSCT). H-Y genotyping was performed in the Regional Blood Center with use of the Dynal Minor Histocompatibility Antigen Typing Kit. H-Y mismatches in the graft-versus-host direction of female donor to male recipient decreased the relapse rate (6% vs 23%; P=.046) and tended to improve disease-free survival (79% vs 44%; P=.067), but it also increased the incidence of chronic graft-versus-host disease (66% vs 38%; P=.02). Thus it influenced the results of alloHSCT from HLA-matched unrelated donors. The results of this study may help to explain the impact of gender differences between donor and recipient in alloHSCT.

The Presence of Anti-HLA Antibodies before and after Allogeneic Hematopoietic Stem Cells Transplantation from HLA-Mismatched Unrelated Donors

Although anti-human leukocyte antigen antibodies (anti-HLA Abs) are important factors responsible for graft rejection in solid organ transplantation and play a role in post-transfusion complications, their role in allogeneic hematopoietic stem cell transplantation (allo-HSCT) has not been finally defined. Enormous polymorphism of HLA-genes, their immunogenicity and heterogeneity of antibodies, as well as the growing number of allo-HSCTs from partially HLA-mismatched donors, increase the probability that anti-HLA antibodies could be important factors responsible for the treatment outcomes. We have examined the incidence of anti-HLA antibodies in a group of 30 allo-HSCT recipients from HLA-mismatched unrelated donors. Anti-HLA Abs were identified in sera collected before and after allo-HSCT. We have used automated DynaChip assay utilizing microchips bearing purified class I and II HLA antigens for detection of anti-HLA Abs. We have detected anit-HLA antibodies against HLA-A, B, C, DR, DQ and DP, but no donor or recipient-specific anti-HLA Abs were detected in the studied group. The preliminary results indicate that anti-HLA antibodies are present before and after allo-HSCT in HLA-mismatched recipients.

Occurrence and Impact of Minor Histocompatibility Antigens' Disparities on Outcomes of Hematopoietic Stem Cell Transplantation from HLA-Matched Sibling Donors

We have examined the alleles of eleven minor histocompatibility antigens (MiHAs) and investigated the occurrence of immunogenic MiHA disparities in 62 recipients of allogeneic hematopoietic cell transplantation (allo-HCT) with myeloablative conditioning performed between 2000 and 2008 and in their HLA-matched sibling donors. Immunogenic MiHA mismatches were detected in 42 donor-recipient pairs: in 29% MiHA was mismatched in HVG direction, in another 29% in GVH direction; bidirectional MiHA disparity was detected in 10% and no MiHA mismatches in 32%. Patients with GVH-directed HY mismatches had lower both overall survival and disease-free survival at 3 years than patients with compatible HY; also higher incidence of both severe acute GvHD and extensive chronic GVHD was observed in patients with GVH-directed HY mismatch. On contrary, GVH-directed mismatches of autosomally encoded MiHAs had no negative effect on overall survival. Results of our study help to understand why posttransplant courses of allo-HCT from siblings may vary despite the complete high-resolution HLA matching of a donor and a recipient.

The kinetics of mRNA transforming growth factor beta1 expression and its serum concentration in graft-versus-host disease after allogeneic hemopoietic stem cell transplantation for myeloid leukemias

Summary Background Graft-versus-host disease (GVHD) is still a major complication following allogeneic hematopoietic stem cell transplantation (alloHSCT). Recent data indicates that transforming growth factor beta1 (TGF-β1) may play a role in development of GVH reaction. Material/Methods Forty patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) were included. Quantitative real time polymerase chain reaction (RT-qPCR) was performed to assess the expression of mRNA TGF-β1. TGF-β1 serum concentration was assessed using a commercial ELISA. Results In all patients, a prompt decrease in TGF-β1 mRNA expression and its serum concentration was demonstrated after conditioning. In patients with acute GVHD, TGF-β1 mRNA expression and its serum concentration remained low until day +30 after transplant as compared to the day of transplant (p<0.03 and p<0.006, respectively). TGF-β1 mRNA expression and its serum concentration significantly increased on day +100 in patients who developed chronic GVHD as compared to the day of transplant (p<0.0009 and p<0.02, respectively). Conclusions TGF-β1 seems to be an additional regulator of donor engraftment; its low levels probably being one of the factors contributing to the development of acute GVHD. On the other hand, chronic GVHD symptoms seem to correlate with high TGF-β1 mRNA expression and its serum concentration in patients who underwent bone marrow transplantation for myeloid leukemias. Nevertheless, further studies with greater numbers of patients are needed to establish the role of TGF-β1 in graft-versus-host disease pathophysiology.

Case-adjusted bortezomib-based strategy in routine therapy of relapsed/refractory multiple myeloma shown to be highly effective—A report by Polish Myeloma Study Group

The observational study was aimed at evaluating response, survival and toxicity of bortezomib-based, case-adjusted regimens in real-life therapy of 708 relapsed/refractory MM patients. Bortezomib was combined with anthracyclines, steroids, thalidomide, alkylators or given in monotherapy. The ORR was 67.9% for refractory and 69.9% for relapsed MM. The median PFS was 14 months and OS 57 months. Patients responding to the therapy had the probability of a 4-year OS at 67.0%. No toxicity was noted in 33.1% of patients. Severe events (grade 3/4) were reported in 35.9% of patients: neurotoxicity (16.7%), neutropenia (9.2%), thrombocytopenia (8.5%), and infections (6.5%). Bortezomib-based, case-adjusted regimens are in real-life practice effective in salvage therapy offering reliable survival with acceptable toxicity for relapsed/refractory MM patients.

Progress in Hematopoietic Stem Cell Transplantation

Transplantation of autologous or allogeneic hematopoietic stem cells is a method currently used to treat many malignant and nonmalignant hematological diseases. The indications, methods, goals of therapy have evolved since the introduction of transplantation to the clini‐ cal practice. Progress that has been achieved allowed for the improvement of results. Thanks to the availability of various conditioning regimens, various hematopoietic cells sources as well as variable possibilities of anti-GvHD prophylaxis the individualization of the trans‐ plantation procedure has been more and more widely used in the recent years. This chapter summarizes current clinical practices and presents major clinical problems that have to be optimally managed in order to improve the outcomes of transplantation.

Early assessment of donor CD34 + positive cells chimerism after allogeneic stem cell transplantation in acute myeloid leukemia/myelodysplastic syndrome patients – pilot study

Introduction. In high-risk acute myeloid leukaemia/myelodysplastic syndrome patients, relapse remains the major cause of treatment failure after allogeneic stem cell transplantation (alloSCT). The investigation of lineage-specific chimerism has become an important tool in the management of patients during the post-transplant period. Aim. Early assessment of lineage specific chimerism in patients who underwent allogeneic hematopoietic stem cell transplantation. Material and methods. 55 patients with acute myeloid leukemia and myelodysplastic syndrome who underwent alloSCT were included in the study. Flow cytometric analysis and cell sorting was performed in bone marrow collected at day 30 after alloSCT. For the purpose of this study we analyzed sorted immature progenitor cells (CD34+CD19-) using STR method. Results. All patients who relapsed presented with lower donor chimerism in CD34+ positive cells in comparison to the group of patients in remission of the underlying disease. Median value of chimerism in CD34+ positive cells in the group of patients who relapsed was 14.5% (range 0-51%), whereas in patients who remained in remission of the underlying disease, chimerism in CD34+ never fell below 97% (median 100%, range 97-100%). All relapses occurred during the first year after alloSCT. Median time to relapse was 107 days (range 28-323). Conclusions. Early assessment of chimerism in CD34+ cells sorted out of bone marrow is a sensitive technique to detect residual or reoccurring disease after allogeneic SCT. The assessment of donor chimerism in CD34+ cells in day +30 after alloSCT seems to be relevant in post-transplant care of high risk patients.

Coexistence of Chronic Lymphocytic Leukemia and Myeloproliferative Neoplasm

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world. Host immune surveillance caused mainly by the disease itself is speculated to be responsible for high incidence of secondary neoplasms. However, the simultaneous occurrence of CLL and myeloproliferative disorder in the same patient is extremely rare. In the present report, a case of an 81-year-old man who was diagnosed with chronic lymphocytic leukemia and concomitant essential thrombocythemia is presented. We describe the morphologic, immunophenotypic, cytogenetic, and molecular findings in this patient. We also review the current literature.

Analiza występowania oraz wpływu przeciwciał anty-HLA u pacjentów po allogenicznym przeszczepieniu komórek krwiotwórczych od częściowo niezgodnych w układzie HLA dawców niespokrewnionych

Streszczenie Przeciwciala skierowane przeciw glownemu ukladowi zgodności tkankowej są istotnym czynnikiem odpowiedzialnym za odrzucenie przeszczepu w przypadku transplantacji narządow litych. Ich wplyw na wyniki allogenicznego przeszczepienia komorek krwiotworczych, szczegolnie od dawcy niezgodnego w ukladzie HLA, nie zostal dotychczas poznany. Wobec wzrastającej liczby allotransplantacji komorek krwiotworczych od dawcow niespokrewnionych nie w pelni zgodnych w ukladzie HLA, zaistniala potrzeba zbadania wystepowania oraz wplywu przeciwcial anty-HLA na wyniki procedury przeszczepowej. Celem naszej pracy bylo zbadanie wystepowania, swoistości oraz wplywu przeciwcial anty-HLA na wyniki przeszczepienia macierzystych komorek krwiotworczych od dawcow niespokrewnionych nie w pelni zgodnych w ukladzie HLA z biorcą przeszczepu. Do badania wlączono 30 pacjentow poddanych transplantacji komorek krwiotworczych w Klinice Hematologii i Transplantacji Szpiku SUM w Katowicach w latach 2001–2007. Przeciwciala anty-HLA byly wykrywane przy uzyciu techniki DynaChip w surowicach pobranych od chorych w roznym czasie od przeprowadzonej procedury przeszczepowej. Technika DynaChip lączy w sobie zmodyfikowaną metode ELISA z techniką microchipow wykorzystującą rozpuszczalne, oczyszczone glikoproteiny HLA zarowno klasy I, jak i II, oplaszczone na powierzchni studzienek. Wstepne obserwacje wskazują, ze po allotransplantacji są wytwarzane przeciwciala skierowane przeciw glownemu ukladowi zgodności tkankowej i mogą one miec potencjalny wplyw na wyniki procedury transplantacyjnej.