Comparision of benefits of early, delayed, and no administration of G-CSF after autologous peripheral blood stem cell transplantation in lymphoma patients.

BACKGROUND: Autologous peripheral blood stem cell transplantation (PBSCT) is commonly used in the treatment of lymphoma patients. G-CSF is widely used to boost white blood cell recovery. However, there are no clear data indicating which strategy of using G-CSF provides the most benefit. The aim of our study was to compare 3 strategies of G-CSF administration: from day +1, from day +5, and no administration. MATERIAL AND METHODS: Data from 211 patients treated at 3 centers were gathered retrospectively. The patients in the 3 analyzed groups were not different in regard to type of disease, age, sex, and number of CD34+ cells received. RESULTS: The 3 strategies of G-CSF dosage had very similar results. G-CSF boosted the recovery of white blood cells and shortened the time of neutropenia. However, there were no differences in confirmed infections and the duration of hospitalization after transplantation. CONCLUSIONS: Our results question the use of G-CSF in a post-PBSCT setting, as it does not provide significant benefits in reducing the number of infections or shortening the duration of hospitalization.

Pure red-cell aplasia following major and bi-directional ABO-incompatible allogeneic stem-cell transplantation: recovery of donor-derived erythropoiesis after long-term treatment using different therapeutic strategies.

Blood group incompatibility between donor and recipient of allogeneic stem cell transplants may be associated with post-transplant erythroid aplasia. A total of 548 patients (pts) received allogeneic transplant for malignant and non-malignant hematologic disorders. In a retrospective analysis, the prevalence and outcome of pure red-cell aplasia (PRCA) in 44 pts with major and bi-directional ABO-mismatch were investigated. Bone marrow grafts were major ABO incompatible in 30 pts; there was bi-directional mismatch in the remaining 14 pts. The median number of transplanted mononuclear cells (NC) was 4.74 x 10(8)/kg (range 0.1-26.4) including CD34+ cells, 3.02 x 10(6)/kg (range 0.9-21.7). Granulocyte engraftment >0.5 x 10e9/l occurred after a median of 21 days (7-32), and platelet exceeded >50 x 10e9/l after a median of 23.5 days (12-109). Acute and chronic graft vs host disease (GVHD) developed in 23 (52%) and 26 (59%) of the patients, respectively. Six (13%) patients transplanted with major and bi-directional ABO-incompatibility developed PRCA. The treatment of PRCA consisted of plasmapheresis (PEX), rapid cyclosporine (CsA) discontinuation, donor lymphocyte infusions (DLI), erythropoietin (EPO), azathioprine, and rituximab. The therapy resulted in erythroid recovery in five out of six patients after a median of 13 months (range 3-16). The median number of transfused red blood cells (RBCs) was 36 U (range 8-57). With a median follow-up of 37 months, the 5-year probability of overall survival (OS) for the PRCA group was 66%. Major ABO mismatch may lead to delayed donor erythroid engraftment. It results in long-term transfusion dependence and, therefore, the risk of iron overload. The therapy is long lasting, but usually effective in majority of patients.

Acute graft-versus-host disease. The incidence and risk factors.

OBJECTIVES: Acute graft-versus-host-disease (aGvHD) is a major cause of mortality after allogeneic hematopoietic cell transplantation (alloHCT). The goal of this study was to evaluate the incidence and risk factors for this complication. METHODS: 330 consecutive patients (183 male and 147 female), aged 29 (10-56) years, treated with alloHCT in a single center between 1992-2003 were included in the analysis. AlloHCT was performed after myeloablative conditioning from either related donor (rel-HCT) (n=223) or unrelated voulnteer (URD-HCT) (n=107). GVHD prophylaxis consisted of cyclosporin, methotrexate +/- prednisolone. RESULTS: Cumulative incidence of grade II-IV and grade III-IV aGvHD equaled 31% and 17%, respectively. In multivariate analysis the following factors were associated with increased risk of grade II-IV aGvHD: the diagnosis of chronic myeloid leukemia (CML) or myelodysplastic syndrome (MDS) (vs. other diagnoses), URD-HCT (vs. Rel-HCT), years of alloHCT 1992-2001 (vs. 2002-2003), donor age > or =35 years, and CD34+ cell dose > or = 4.0 x 10(6)/kg. Increased risk of grade III-IV aGVHD was associated with: the use of prednisolone for aGvHD prophylaxis, the diagnosis of CML or MDS, and CD3+ cell dose > or =100 x l0(6)/kg. CONCLUSIONS: Incidence of aGvHD depends on various recipient-, donor-, and procedure-related factors. This should be taken into account when planning treatment for every individual patient.

[Impact of chronic graft-versus-host disease on long-term outcome after allogeneic hematopoietic cell transplantation in adult acute lymphoblastic leukemia]. / Wplyw przewleklej choroby przeszczep-przeciw-gospodarzowi na odlegle wyniki allogenicznej transplantacji komórek krwiotwórczych u doroslych chorych na ostra bialaczke limfoblastyczna.

Chronic graft-versus-host-disease (cGVHD) is a major cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation (alloHCT). However, it may be accompanied by graft-versus-leukemia (GVL) reaction contributing to decreased risk of relapse. The aim of this study was to evaluate the influence of cGVHD on outcome of adult acute lymphoblastic leukemia (ALL) patients treated with alloHCT. Fifty-five ALL patients, aged 24 (18-54) years, who survived without progression at least 100 days after alloHCT from HLA-identical sibling (n = 40, 73%) or an unrelated volunteer (n = 15, 27%) were included in the analysis. 24 patients 44% were given alloHCT in first complete remission, whereas the remaining 31 patients (44%) were in more advanced disease. The probability of overall survival (OS) and disease-free survival (DFS) equaled 57% and 48% at 8 years, respectively. Cumulative incidence of relapse and non-relapse mortality (NRM) was 39% and 13%, respectively. OS rate equaled 51% for patients without cGVHD, 94% for patients with limited cGVHD, and 38% for those with extensive cGVHD. In the respective subgroups relapse incidence was 60%, 9% and 0%, whereas the incidence of NRM equaled 3%, 6% and 62%. In multivariate analysis the lack of cGVHD was the most important factor associated with increased risk of relapse and deteriorated DFS. Extensive, but not limited cGVHD was associated with increased risk of NMR. Our findings confirm that in adults with ALL, cGVHD is accompanied by a strong GVL reaction. Induction of limited cGVHD may constitute the most effective prophylaxis of relapse in this group of patients.

Treosulfan, cyclophosphamide and antithymocyte globulin for allogeneic hematopoietic cell transplantation in acquired severe aplastic anemia.

To reduce the risk of graft rejection after allogeneic hematopoietic cell transplantation (alloHCT) for patients with acquired severe aplastic anemia (SAA), we introduced an intensified preparative regimen consisting of treosulfan 10 g/m2/d on days -7, -6, cyclophosphamide 40 mg/kg/d on days -5, -4, -3, -2 and anti-thymocyte globulin 2 mg/kg/d on days -3, -2, -1. Six patients with the history of multiple transfusions were treated with alloHCT from either HLA-identical sibling (n=3) or an unrelated volunteer (n=3). Each, bone marrow and peripheral blood was used as a source of stem cells in three cases. All patients engrafted and achieved complete donor chimerism. None of the patients experienced severe organ toxicity. No severe acute graft-versus-host-disease (GVHD) was observed; two patients experienced extensive chronic GVHD. At the median follow-up of 14.5 (13-27) months all patients remained alive and disease-free. Our observation indicates that treosulfan + cyclophosphamide + antithymocyte globulin conditioning is well-tolerated and allows stable engraftment in acquired SAA.

Homozygosity for human leucocyte antigen-C ligands of KIR2DL1 is associated with increased risk of relapse after human leucocyte antigen-C-matched unrelated donor haematopoietic stem cell transplantation.

Human leucocyte antigen (HLA)-C molecules regulate the function of natural killer cells and may be subdivided into two groups, C(1) and C(2), based on their specificity for inhibitory killer immunoglobulin-like receptors. We analysed the impact of the HLA-C genotype on outcome of HLA-C-matched unrelated donor haematopoietic stem cell transplantation (URD-HSCT) recipients. HLA-C(2) homozygous patients (n = 18) had lower probability of overall survival (P = 0.01) and disease-free survival (P = 0.02), resulting from increased relapse rate (P = 0.02) when compared with both HLA-C(1) homozygous (n = 43) and HLA-C(1),C(2) heterozygous (n = 50) subgroups. Patients lacking HLA-C(1) should, therefore, be considered at increased risk of relapse following HLA-C-matched URD-HSCT.

The impact of immunosuppressive therapy on an early quantitative NK cell reconstitution after allogeneic haematopoietic cell transplantation.

OBJECTIVES: The goal of this study was to examine the impact of various immunosuppressive regimens on an early NK cell recovery following haematopoietic cell transplantation (alloHCT). METHODS: The number of peripheral blood NK cells was analysed with the use of flow cytometry on day +30 (+/-2) after alloHCT from an HLA identical sibling (n=43) or an unrelated (n=34) donor. RESULTS: Patients receiving prednisolone as a prophylaxis of acute graft-versus-host disease had lower number of NK cells compared to those not given steroids prophylactically (110(10-694) vs. 212(33-890) x 10(6)/L, p = 0.005). In contrast, administration of anti-thymocyte globulin (ATG) (7.5-15 mg/kg) as a part of preparative regimen was not found to influence the NK cell recovery. Similarly, no effect on the number of peripheral blood NK cells was observed with regard to other analysed factors: cell dose, type of myeloablative conditioning, source of stem cells, patient and donor characteristics, number of post-transplant methotrexate doses. CONCLUSIONS: Immunosuppressive therapy may affect NK cell recovery following alloHCT. Since NK cells are considered a potential tool for cellular therapy of haematological malignancies, our findings should be taken into account when planning this kind of treatment in the context of allotransplantation.

First two successful unrelated donor bone marrow transplantations for paroxysmal nocturnal hemoglobinuria in Poland.

OBJECTIVES: The experience with bone marrow transplantation (BMT) from matched unrelated donors (MUD) for paroxysmal nocturnal hemoglobinuria (PNH) is limited and optimal preparative regimen has been not established. METHODS: We report first two MUD BMTs for patients with PNH in Poland. Preparative regimen consisted of Treosulfan, Fludarabine and Thymoglobulin. We also present the review of published reports on allogeneic transplantations for PNH and discuss important transplant-related issues. RESULTS: Both patients are alive and are doing well over 12 and over 4 months following BMT. Regeneration is complete with full 100% donor chimerism and the eradication of PNH clone. CONCLUSIONS: MUD BMT is an effective treatment for PNH. Treosulfan, Fludarabine and Thymoglobulin treatment can be safely and effectively used for conditioning in PNH.

Assessment of chosen parameters of the immune system in children with acute lymphoblastic leukemia.

The immunosuppressive effect of cytostatics, basic therapeutic agents in the treatment of proliferative diseases of the hematopoietic system, and the rising number of children cured from acute leukaemias form together a need to monitor the status of the immune system following cessation of therapy. Surface antigens in lymphocytes from peripheral blood were assessed in 16 children directly after intensive chemotherapy (i.e., after protocol II of the BMF program) and in 25 children 12-13 months following conclusion of acute lymphoblastic leukemia treatment. The results were compared to data obtained from children never afflicted with neoplastic disease. A significant decrease in the average number of lymphocyte subpopulations was noted in the case of the treated children directly after intensive chemotherapy. The average values of lymphocyte subpopulations in children with concluded treatment are within the norm, with the exception of NK and TS lymphocytes.

[T lymphocyte alpha/beta and gamma/delta in peripheral blood of children with acute lymphoblastic leukemia]. / Limfocyty T alfa/beta i gamma/delta we krwi obwodowej u dzieci chorych na ostra bialaczke limfoblastyczna.

The improvement in acute lymphoblastic leukemia (ALL) children treatment results in the need of examining their immune system after therapy. The purpose of the research was the immune system evaluation in children with low risk ALL diagnosis, during the treatment and twelve months after therapy. The examined material included 41 children. A group of 16 patients was examined during the above the treatment, immediately after intensive chemotherapy. The other 25 patients were examined twelve months after the completion of therapy. The lymphocyte immune phenotype was examined with FACScan flow cytometer using monoclonal antibodies. The study confirmed the intensive chemotherapy significantly decreases the number of leukocytes, lymphocytes and their subpopulations. The period of 12 months after cessation of the chemotherapy is sufficient to recover the immune system function in all examined low risk ALL children.