Donor's age influences outcome in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide - a single center experience.

Haploidentical stem cell transplantation (haplo-SCT) using post-transplantation cyclophosphamide (post-Cy) is considered a reasonable therapeutic option for patients who lack matched donor or who urgently need transplant procedure due to high risk disease. We analyzed the results of haplo-SCT performed in years 2018-2023. Eighty one patients (46 males) at median age of 52 years underwent haplo-SCT using peripheral blood as a stem cell source in most cases. Indications included hematological malignancies (acute leukemias in 88% of cases). In 25 cases (31%) transplantation was performed in relapsed/refractory disease. Majority of patients (61%) presented with very high and high disease risk index (DRI). Conditioning regimens were as follows: nonmyeloablative - 46 cases (57%), myeloablative - in 18 (22%) and reduced intensity - 17(20%). 90% of patients engrafted. All patients received unified immunosuppressive treatment (post-Cy/TAC/MMF). Median follow-up time was 12 months The cumulative incidence of acute and chronic GVHD was 37.5% and 37.6%, respectively. Estimated 2-year overall survival (OS) was 43.1% and donor's age was the only factor influencing survival. The 2-year progression-free survival (PFS) was 42.5%, whereas relapse incidence (RI) - 35%. The cumulative incidence of non-relapse mortality (NRM) was 44% and was mostly due to infections. Haplo-SCT is a feasible treatment option for hematological patients. Younger donor improves post-transplant survival. Strategies to reduce infection-related mortality and relapse rate remain a challenge.

Real-Life Data on the Efficacy and Safety of Letermovir for Primary Prophylaxis of Cytomegalovirus in Allogeneic Hematopoietic Stem Cell Recipients: A Single-Center Analysis

Objective: Cytomegalovirus (CMV) reactivation is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Introduction of letermovir (LMV) seems to improve post-transplant outcomes, but delayed-onset CMV reactivation still remains a challenge. In this study, we report on our first experience with LMV prophylaxis in 93 CMV-seropositive adult patients receiving HSCT in our center. Materials and Methods: We retrospectively analyzed the data of 93 adult CMV-seropositive recipients receiving LMV as CMV prophylaxis after HSCT for hematological malignancies between 2019 and 2023. The starting LMV dose was 480 mg daily, reduced to 240 mg daily for those receiving cyclosporin A co-administration. CMV DNA in the blood was measured by real-time polymerase chain reaction weekly for the first 2 months after transplantation, then every other week until the end of immunosuppressive treatment. LMV was continued to day +100 or to CMV reactivation. Results: The median recipient age at the time of transplant was 51 (range: 20-71) years. All patients received grafts from peripheral blood, mostly for acute myeloid leukemia (60%). The median time from transplantation to LMV initiation was 3 (range: 0-24) days. While 55% of patients were transplanted from matched related donors, 32% had unrelated donors and 13% underwent haploidentical HSCT. Four patients (4%) had CMV "blips" while on LMV, but the drug was continued and repeated assays were negative. Only 2 patients (2%) experienced CMV reactivation while on LMV, on days 48 and 34 after HSCT, respectively. Seven patients (7%) developed late-onset CMV reactivation after a median of 124 days after HSCT (range: 118-152 days) and they were successfully treated with ganciclovir. CMV disease was not observed. Grade III-IV acute graft-versus-host disease occurred in 6 patients (6%) during LMV treatment. LMV treatment was free of side effects. Conclusion: LMV prophylaxis was effective in preventing CMV reactivation with a favorable safety profile. CMV reactivation occurred mostly after LMV discontinuation; thus, extending the duration of prophylaxis beyond 100 days could be beneficial.

Effect of transplanted cells with CD184 and CD26 expressions and reconstitution of CD3+ lymphocyte population on long-term survival after autologous hematopoietic stem cell transplantation for multiple myeloma.

Autologous hematopoietic stem cell transplantation (auto-SCT) is the recommended treatment for responding patients with multiple myeloma (MM). However, we do not know the risk factors influencing long-term survival without progression after auto-SCT. Therefore, this prospective study aimed to investigate the influence of transplanted cells with cluster of differentiation (CD)184+ expression, CD26+ lymphocytes and monocytes, and reconstitution of CD3+ lymphocytes on overall survival (OS) and progression-free survival (PFS) after auto-SCT in MM. Forty-eight patients with MM underwent auto-SCT at our center from 2011 to 2013. The numbers of CD184+ cells, CD26+ lymphocytes, and CD26+ monocytes were measured in the harvested material. In addition, the number of lymphocyte subpopulations (CD3+ lymphocytes, helpers, suppressors, natural killer (NK), cytotoxic NK, and B lymphocytes) was measured in peripheral blood during regeneration after auto-SCT. Flow cytometry was performed in both cases. The median OS was 92 months. Our analysis revealed a statistically significant effect of the number of transplanted CD184+ cells on OS and a statistically significant correlation between PFS and the number of transplanted CD184+ cells and reconstitution of CD3+ lymphocytes. In conclusion, our study showed that the increasing numbers of transplanted CD184+ cells, CD26+ lymphocytes, and CD26+ monocytes augmented the risk of death.

Double Malignancy and Double Transplant-A Bumpy Road to Success.

The occurrence of secondary neoplasms in adult patients treated with chemotherapy in childhood is not uncommon. Prior chemotherapy is found to be an independent risk factor for the development of secondary malignancies, which are usually associated with a worse prognosis. The presented case is a 35-year-old female patient who was diagnosed with Ewing sarcoma in her late adolescence. The tumor was successfully treated with chemotherapy, but 3 years later she was diagnosed with T-cell lymphoblastic lymphoma. The patient received allogeneic hematopoietic stem cell transplantation (allo-HSCT) from human leukocyte antigen (HLA) matched related donor. The procedure was complicated by grade 2 acute graft-versus-host disease (GvHD) which resolved after implementation of immunosuppressive treatment. However, a year later, the patient developed extensive chronic GvHD (cGvHD) and required reintroduction of immunosuppressants. Prolonged immunosuppressive treatment with tacrolimus led to irreversible kidney failure. After a 2-year period of regular peritoneal dialysis, she was found to be eligible for a kidney transplant from a deceased donor. Now, 15 years after stem cell transplantation and 8 years after kidney transplantation, the patient remains in good condition overall, presenting with symptoms of limited cGvHD. The case described here presents a unique clinical scenario of a female patient who was successfully treated for her double malignancy. Moreover, she underwent effective double transplantations and was eventually found to be cured despite accompanying complications.

Allogeneic hematopoietic stem cell transplantation remains a feasible approach for elderly with acute myeloid leukemia: a 10-year experience.

The incidence of AML increases with age. The implementation of reduced intensity conditioning and progress in supportive care enabled to perform allo-HSCT in elderly patients. The main objective of the study was to assess the safety and efficacy of allotransplantation in elderly AML.Forty nine patients (33 males) at median age of 68 years were identified. Data on patients' and transplant's related variables were retrieved from our local transplant registry. Most patients (65%) were transplanted from 10/10-HLA or 9/10-HLA matched unrelated donor, seven patients (14%) received stem cells from matched related donor and ten patients (20%) from haploidentical donor. All patients received reduced-intensity conditioning (RIC). Peripheral blood was a source of stem cells in all patients except one (98%). Acute GVHD developed in 22 patients (44%) with 5 individuals presenting grade III-IV. CMV reactivation was demonstrated in 19 patients (39%) till day + 100. In total, 22 patients (45%) have died. The main causes of death included infectious complications (n = 9), relapse with subsequent chemotherapy resistance (n = 7), steroid-resistant GvHD (n = 4) and other causes (n = 2). Twenty-seven patients (55%) were alive at the last contact, presented full donor chimerism and remained in the complete remission. The probability of OS and relapse-free survival (RFS) were 57% and 81% at 2 years, respectively. Older donor age showed negative impact on relapse. CMV reactivation, the severity of acute graft versus host disease and older donor age negatively influenced survival. Allo-HSCT remains a safe, feasible and effective procedure for elderly AML patients.

Allogeneic hematopoietic stem cell transplantation for acquired severe aplastic anemia: a summary of a 20-year experience.

INTRODUCTION: Severe aplastic anemia (SAA) is a rare but potentially fatal disorder characterized by hypocellular bone marrow and resulting in pancytopenia. It can be cured with allogeneic hematopoietic stem cell transplantation (allo­HSCT), especially in young individuals. OBJECTIVES: The main objective of the study was to assess the safety of the procedure and to identify the factors influencing long­term post­transplant outcome. PATIENTS AND METHODS: Using our institutional database, we performed a retrospective analysis of the patients with SAA allotransplanted in the years 2001-2021. RESULTS: Seventy patients (49 men) at a median age of 25 years at transplantation underwent allo­HSCT. Thirty-eight patients received immunosuppressive treatment (IST) before transplantation. Twenty-one patients received grafts from human leukocyte antigen-matched sibling, 44 from unrelated donors, and 5 from haploidentical related donors. Peripheral blood remained the source of stem cells in the majority of patients. Primary graft failure was observed in 2 cases. The incidence of acute graft­versus­host disease (GVHD) was 44%, whereas chronic GVHD was observed only in 4 patients. Median follow­up was 3 years (interquartile range, 0.45-11.5). Post­transplant outcome was comparable between patients with upfront allo­HSCT and those who relapsed after IST. In the univariable analysis, only a higher Eastern Cooperative Oncology Group (ECOG) score at transplantation and infections in the post­transplant period were found to be associated with unfavorable outcome. Fifty­three patients were alive at last contact. Most transplanted patients died due to infectious complications. A 2­year overall survival was 73%. CONCLUSIONS: The results of allo­HSCT in SAA are satisfactory and offer long­term survival and good quality of life. Higher ECOG score and the presence of infections are associated with poor post­transplant outcome.

Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed/Refractory Acute Myeloid Leukemia: A Single-Centre Experience.

INTRODUCTION: Patients with relapsed/refractory acute myeloid leukemia (r/r AML) are characterized as having a poor prognosis. The only viable option of treatment for these patients is allogenic stem cell transplantation (allo-HSCT). Therefore, we have attempted to analyse factors related to both the disease itself and the transplantation procedure that could have an influence on the improvement of outcomes in this group of patients. PATIENTS AND METHODS: Sixty-four patients with r/r AML underwent allo-HSCT at our center in 2012 to 2021. Fifty-two had active disease at the beginning of theallo-HSCT procedure, with amedian number of blasts in bone marrow (BM) of 18, and 12 had therapeutic aplasia after the last reinduction (blasts < 5% in BM). RESULTS: The probability of overall survival (OS) at 2 years was 25%. The median follow-up for survivors was 21.5 months. Progression-free survival (PFS) estimates were above 46%. The main cause of death was disease progression (49%). A statistically significant effect on premature death was reported for the diagnosis of secondary AML (sAML) and cytomelovirus (CMV) reactivation post allo-HSCT. On the other hand, chronic graft versus host disease (cGVHD) decreased the risk of disease progression. sAML and CMV reactivation were found to have opposite effects.

Room for Improvement: A 20-Year Single Center Experience with Allogeneic Stem Cell Transplantation for Myelodysplastic Syndromes.

Allogeneic stem cell transplantation (allo-SCT) remains the only curative therapeutic approach for patients with myelodysplastic syndromes (MDS). The aim of the study was to assess the efficacy/safety of allo-SCT as well as to identify factors influencing post-transplant survival. One hundred and two MDS patients (median age: 48 years; 57 males) who underwent allo-SCT were retrospectively evaluated. Twenty seven patients were transplanted from HLA-matched sibling and 75 patients received grafts from unrelated donors. Peripheral blood was a source of stem cell for 79 patients. Reduced intensity conditioning was used in 64 subjects. Acute and chronic graft versus host disease (GvHD) developed in 61 and 19 of patients, respectively. In total, 61 patients have died. The causes of deaths included infectious complications (n = 30), steroid-resistant GvHD (n = 17), MDS relapse (n = 9) and transformation to AML (n = 5). Non-relapse mortality and cumulative incidence of relapse at 2 years were 49.8% and 9%, respectively. 41 patients are alive at last contact and present full donor chimerism. 38 patients remain in complete hematological remission (CHR), 3 patients had CHR with incomplete platelet recovery. Median follow-up from diagnosis of MDS and transplantation are 27.1 months and 7 months respectively. Overall survival and relapse-free survival were 41% at 2 years. Increased serum ferritin level > 1000 ng/ml, presence of acute GvHD, grades III-IV acute GvHD and high hematopoietic cell transplantation-comorbidity index were found to negatively influenced survival. Allo-SCT for MDS is feasible procedure with a proportion of patients to be cured.

Real-world experience with ruxolitinib for steroid-refractory acute graft-versus-host disease: a single center experience.

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ruxolitinib (RUX), an oral JAK1 and JAK2 inhibitor, has recently been approved for patients with SR-aGVHD. The aim of this study was to evaluate RUX efficacy and toxicity in a real-world setting. Eighteen patients received RUX at 5 mg or 10 mg twice a day after a median 3 lines of prior unsuccessful immunosuppressive therapy. Median time on RUX therapy was 28 days (range 7-129). Five patients (28%) responded to RUX, including 4 complete responses and 1 partial response. Response to RUX was irrespective of aGVHD grade and the number of involved organs. One-year overall survival (OS) was 60% for RUX-responders versus 31% for non-responders (p = ns). Treatment duration greater than 29.5 days was found to have a positive impact on OS (p < 0.007). Major adverse events during RUX treatment were grade 3-4 thrombocytopenia (61% of patients) and cytomegalovirus reactivation (50%). After median follow-up of 55 days (range 29-706), 14 patients (78%) died, mainly due to further progression of GVHD. RUX may represent a valuable therapeutic option for some patients with advanced SR-aGVHD, but more studies are warranted.

The Potential Role of Proinflammatory Cytokines and Complement Components in the Development of Drug-Induced Neuropathy in Patients with Multiple Myeloma.

The launch of novel chemotherapeutic agents-in particular, proteasome inhibitors and immunomodulatory drugs-dramatically changed multiple myeloma (MM) therapy, improving the response rate and prolonging progression-free survival. However, none of the anti-MM drugs are deprived of side effects. Peripheral neuropathy (PN) seems to be one of the most pressing problems. Despite extensive research in this area, the pathogenesis of drug-induced peripheral neuropathy (DiPN) has not yet been fully elucidated. In the present study, we aimed to assess the potential relationship between proinflammatory factors and the development of PN in MM patients with particular emphasis on the application of VTD (bortezomib, thalidomide, dexamethasone) regimen. Our analysis identified increased concentrations of CCL2, IL-1ß, and IFN-γ in plasma of MM patients during treatment, both with and without symptoms of PN, compared with untreated neuropathy-free MM patients. At the same time, the plasma concentration of IL-1ß in patients with neuropathy was significantly increased compared with patients without PN before and during treatment. Moreover, the results were enhanced at the transcript level by performing global mRNA expression analysis using microarray technology. The most significant changes were observed in the expression of genes responsible for regulating immunological and apoptotic processes. An in-depth understanding of the mechanisms responsible for the development of DiPN might in the future reduce the incidence of PN and accelerate diagnosis, allowing the choice of neuropathy-free treatment strategies for MM.

The Efficacy of Cladribine (2-CdA) in Advanced Systemic Mastocytosis.

Systemic mastocytosis (SM) is a rare clonal disorder with multi-organ involvements and shortened life expectancy. To date, no curative treatment for SM exists. Cladribine (2-CdA) is a purine analogue showing activity against neoplastic mast cells and its use was found to be effective in some patients with SM. Nine patients (six males and three females) with advanced SM at median age of 63 years (range 33-67) who received at least one course of 2-CdA were included in a retrospective analysis. Study patients were classified as having aggressive SM (ASM; n = 7) and SM with an associated hematological neoplasm (SM-AHN; n = 2). The "C" findings were as follows: (1) absolute neutrophil count (ANC) < 1 × 109/l (n = 1) and/or hemoglobin level < 10 g/dl (n = 4) and/or platelet count < 100 × 109/l (n = 4); (2) hepatomegaly with ascites (n = 4); (3) skeletal involvement (n = 2); (4) palpable splenomegaly with hypersplenism (n = 3) and (5) malabsorption with weight loss (n = 5). Treatment consisted of 2-CdA at dose 0.14 mg/kg/day intravenously over a 2-h infusion for 5 consecutive days. Median dose per cycle was 45 mg (range 35-60). Median number of cycles was 6 (range 1-7). Overall response rate (ORR) was 66% (6/9 pts) including three partial responses and three clinical improvements. ORR was 100% and 66% for SM-AHN and ASM, respectively. Median duration of response was 1.98 years (range 0.2-11.2). At the last contact, five patients died, four have little disease activity, but remain treatment- free. 2-CdA seems to be beneficial in some patients with SM, however the response is incomplete.

Pre-transplant FLT3/ITD status predicts outcome in FLT3-mutated acute myeloid leukemia following allogeneic stem cell transplantation.

Acute myeloid leukemia (AML) with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is associated with poor prognosis, and allogeneic stem cell transplantation (Allo-SCT) seems to be the preferred therapeutic approach. However, the predictors of post-transplant outcomes were not well-defined. The aim of the study was to evaluate the significance of FLT3/ITD mutation by polymerase chain reaction as minimal residual disease (MRD) marker of outcomes after transplantation. We identified 43 patients (28 females and 15 males) with FLT3-mutated AML at the median age of 45 years who were allografted between 2009 and 2019. Hematological status at transplant was as follows: the first complete remission (CR1) in 29 patients, CR2 in 5, and 9 patients were transplanted in marrow aplasia (MA). Twenty-seven patients were FLT3 MRD negative at transplant. Median time from diagnosis to transplant was 16.7 months. Post-allograft CR rate was 88%. The relapse incidence (RI) was lower for patients who were FLT3 MRD negative at transplant when compared with those with FLT3 MRD positivity (41% vs 59%; p = 0.01). The patients who eradicated FLT3/ITD at day + 30 after transplant had lower RI than those with detectable FLT3/ITD (23% vs 76%; p = <0.001). The 2-year LFS and OS were 53% and 54%, with the median OS and LFS of 28 months and 27 months, respectively. Patients with CR1/2 and FLT3 MRD(-) had a 2-year OS of 80%. The FLT3 MRD negativity at transplant prolonged LFS in multivariate analysis (HR 5.3 95%CI 1.97-14.2); p < 0.001), whereas FLT3 MRD negativity and unrelated donor predicted favorable OS.

Autologous stem cell transplantation in the treatment of multiple myeloma with 17p deletion.

INTRODUCTION: Deletion of chromosome 17p [del(17p)] in patients with multiple myeloma is associated with a poor prognosis. High­dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains the standard of treatment in this population. OBJECTIVES: The aim of the study was to compare the treatment outcomes with high­dose chemotherapy and ASCT with standard treatment in patients with del(17p). PATIENTS AND METHODS: We collected data from 12 Polish centers between 2011 and 2017. The records of 97 patients with p53 deletion were assessed, including 29 individuals treated with ACST and 68 receiving standard treatment alone. RESULTS: During the follow­up, 45 patients died and the overall survival (OS) for the whole group was 33 months (range, 1-66 months), with a median progression­free survival (PFS) of 13 months (range, 1-46 months). The prognostic factors of OS in a multivariable analysis were calcium levels at diagnosis within the reference range (hazard ratio [HR], 0.24; 95% CI, 0.12-0.48) and at least partial remission achieved after the first­line treatment (HR, 0.25; 95% CI, 0.12-0.51). Treatment with ASCT was an important factor in improving survival (HR, 3.23; 95% CI, 1.52-6.84). Abnormal kidney function at the time of diagnosis reduced the PFS (HR, 0.46; 95% CI, 0.22-0.94). When the analysis was limited only to patients who could be candidates for ASCT, the survival benefit of the procedure was lost (P = 0.21). CONCLUSIONS: Patients with multiple myeloma with del(17p) do not benefit from high­dose chemotherapy followed by ACST.

Allogeneic transplantation for high-risk chronic lymphocytic leukemia-a summary of a 16-year experience.

In the pathway inhibitor era, the number of allogeneic stem cell transplantation (ASCT) for chronic lymphocytic leukemia (CLL) continues to decrease and this approach should be offered only after careful risk-benefit assessment. Nevertheless, ASCT still remains only curative therapeutic modality for CLL, especially in countries with limited access to novel agents. Thirty patients with CLL at median age of 42 years at diagnosis (range 29-64) underwent ASCT between years 2002 and 2018. Thirteen patients were transplanted in complete remission (CR), ten patients achieved partial response (PR), and seven had stable disease. The median time from diagnosis to transplant was 4 years (range 0.5-12). Twenty-three patients received HLA-matched related donor stem cell grafts, and seven patients received either matched unrelated donor or HLA-mismatched grafts. Reduced intensity conditioning (RIC) and myeloablative regimen (MAC) were used in 24 and 6 patients, respectively. Mortality to day + 100 after transplant was 16% (8% for RIC only). Acute and chronic graft versus host disease (GVHD) developed in 40% and 63% of patients, respectively. Fifteen patients relapsed or progressed after transplant. Thirteen patients (43%) are alive at last follow-up and 10 (77%) remain in clinical CR. Median follow-up for survivors was 6.8 years (range 0.4-15.2). Three-year progression-free and overall survivals were 56% and 60%, respectively. These outcomes were better for patients who received RIC conditioning: 64% and 72%, respectively. CR at transplant was found to have favorable impact on post-allograft survival. RIC should be preferred over MAC. ASCT may remain a valuable option for some CLL patients.

Splenic irradiation before allogeneic stem cell transplantation for myelofibrosis.

Splenectomy before allogeneic stem cell transplantation (ASCT) for patients with myelofibrosis (MF) remains a matter of debate, and conflicting results have been reported to date. The procedure seems to fasten post-transplant hematological recovery, but it does not have an impact on survival. The role of pre-transplant splenic irradiation (SI) is much more difficult to evaluate. Forty-four patients (25 males and 19 females) with MF at median age of 49 years at diagnosis (range 14-67) underwent ASCT. The post-transplant outcome was compared between irradiated and non-irradiated patients. Eleven patients received irradiation before transplantation. Median dose of radiation was 1000 cGy (range 600-2400). There was no difference in median time to engraftment between patients with and without previous radiotherapy. Acute and chronic graft versus host disease (GVHD) occurred in 47% and 36% of patients, respectively. There was no difference in GVHD incidence between groups. Eight patients relapsed/progressed in irradiated group versus 17 in non-irradiated (70% vs. 51%; p = 0.3). Transformation to acute myeloid leukemia was observed in 3 patients: 2 in irradiated and 1 in non-irradiated group. In total, 22 patients died with no statistical difference in death rate between irradiated and non-irradiated subjects. The probability of overall survival after transplant for the entire cohort at 2 years was 54% (72% for irradiated and 48% for non-irradiated patients; p = 0.25). Splenic irradiation prior to ASCT for myelofibrosis has not beneficial effect on post-transplant outcome.

Real Life Data on Efficacy and Safety of Azacitidine Therapy for Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia.

The administration of azacitidine (AZA) was found to be more effective than conventional care regimen (CCR) in patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) with lower blast count. We designed a study to determine efficacy and safety of AZA therapy in "real life" patients with MDS, CMML and AML. The study included 83 patients (65% male) with a median age at diagnosis of 68 years. 43 patients were diagnosed with higher-risk MDS, 30 had AML and 10-CMML. Median AZA dose was comparable between treated groups. AZA dose reduction was required for 44% of MDS, 17% of AML and 25% of CMML patients. Complete remission (CR) was achieved in 14% of MDS, 7% of AML and 10% of CMML patients. Overall response rate was following: 27% for MDS, 20% for AML and 20% for CMML. Estimated OS at 12 months was 75% for MDS, 60% for AML and 75% for CMML. Median follow-up for MDS/AML/CMML from AZA initiation to last follow-up was 9.0, 9.4 and 9.4 months, respectively. The most common toxicity of AZA therapy was myelosuppression and infections. AZA treatment was effective in a limited number of patients with acceptable safety profile.

HLA-inferred extended haplotype disparity level is more relevant than the level of HLA mismatch alone for the patients survival and GvHD in T cell-replate hematopoietic stem cell transplantation from unrelated donor.

Serious risks in unrelated hematopoietic stem cell transplantation (HSCT) including graft versus host disease (GvHD) and mortality are associated with HLA disparity between donor and recipient. The increased risks might be dependent on disparity in not-routinely-tested multiple polymorphisms in genetically dense MHC region, being organized in combinations of two extended MHC haplotypes (Ehp). We assessed the clinical role of donor-recipient Ehp disparity levels in N = 889 patients by the population-based detection of HLA allele phase mismatch. We found increased GvHD incidences and mortality rates with increasing Ehp mismatch level even with the same HLA mismatch level. In multivariate analysis HLA mismatch levels were excluded from models and Ehp disparity level remained independent prognostic factor for high grade acute GvHD (p = 0.000037, HR = 10.68, 95%CI 5.50-32.5) and extended chronic GvHD (p < 0.000001, HR = 15.51, CI95% 5.36-44.8). In group with single HLA mismatch, patients with double Ehp disparity had worse 5-year overall survival (45% vs. 56%, p = 0.00065, HR = 4.05, CI95% 1.69-9.71) and non-relapse mortality (40% vs. 31%, p = 0.00037, HR = 5.63, CI95% 2.04-15.5) than patients with single Ehp disparity. We conclude that Ehp-linked factors contribute to the high morbidity and mortality in recipients given HLA-mismatched unrelated transplant and Ehp matching should be considered in clinical HSCT.

The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell Transplantation.

CD86 molecule is the ligand for both costimulatory (CD28) and coinhibitory (CTLA-4) molecules, and it regulates immune response after allogeneic hematopoietic stem cell transplantation (alloHSCT). Therefore, we postulate that CD86 gene variations might influence the outcome after alloHSCT. Altogether, 295 adult patients (pts) undergoing related (105 pts) and unrelated (190 pts) donor-matched HSCT were genotyped for the following CD86 gene polymorphisms: rs1129055, rs9831894, and rs2715267. Moreover, the donors' rs1129055 polymorphism was determined. None of the investigated SNPs alone were associated with aGvHD and rate of relapse. However, we showed that rs2715267 SNP influenced overall survival (OS) after alloHSCT. The 24-month OS for the rs271526GG recipients was worse than that for the recipients possessing T allelle (TT or GT genotypes) (p = 0.009). Moreover, analysis of gene-gene interaction between CD86 and CTLA-4 showed that having both the A allele for CD86 rs1129055 and the CTLA-4 CT60GG genotype in recipients increased the risk of aGvHD about 3.5 times. Interestingly, the donors' rs1129055GG genotype and the recipients' CT60GG genotype also increased the risk of aGvHD about 2.7-fold. We postulate that recipients' CD86 gene polymorphisms influence the overall survival after alloHSCT and, together with CTLA-4 polymorphisms, might be considered a risk factor for aGvHD.

Long-Term Outcome of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Acute Myeloid Leukemia (AML)- Single Center Retrospective Analysis.

For patients with acute myeloid leukemia (AML) in complete remission without an acceptable HLA donor, the autologous hematopoietic stem cell transplantation (AHSCT) may remain a therapeutic option as remission consolidation, however its role is still a subject of continued debate. One hundred and twenty patients who underwent AHSCT for AML were included in this retrospective single center analysis. The procedure was performed over a 19 years period and transplanted patients were in first complete remission (CR1; n = 109) or in second CR (CR2; n = 11). The median age at transplant was 37 years (range 18-64). The source of stem cells was bone marrow (n = 61; 50.8%), peripheral blood (n = 36; 30%) and bone marrow with peripheral blood (n = 23; 19.2%). The median time from AML diagnosis to AHSCT was 0.8 year (range 0.3-4.4) and the median follow-up after AHSCT for surviving patients was 12.8 years (range 3.1-20.5). The median LFS was 1.1 year. The probability of LFS calculated at 5 years and 10 years after transplantation was 28% (95%CI, 22%-32%) and 21% (95%CI, 18%-24%), respectively. The last relapse occurred 14.8 years after AHSCT and among patients who survived >2 years, 28.4% (27/95) had leukemia recurrence. The median OS was 1.7 years. The probability of OS after 5 years and 10 years was 29% and 22%, respectively. There was a tendency for increased LFS for patients younger than 50 years at transplant if compared to older population. AHSCT for AML was safe with acceptable toxicity profile. Leukemia recurrence remained the leading cause of death.

Safety profile of autologous hematopoietic stem cell mobilization and transplantation in patients with systemic sclerosis.

Autologous hematopoietic stem cell transplantation (AHSCT) is thought to be effective therapeutic approach in patients with poor prognosis systemic sclerosis; however, the toxicity remains a challenge. Between years 2003 and 2016, we enrolled 18 patients with systemic sclerosis at median age at transplant of 52 years (range 24-68). The median duration of disease before AHSCT was 14 months (range 2-85). Peripheral blood stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. Conditioning regimen included CY (200 mg/kg) and alemtuzumab (median dose, 60 mg) [n = 11], melphalan (MEL; 140 mg/m2) and alemtuzumab [n = 2], CY and rabbit anti-thymocyte globulin (rATG; 7.5 mg/kg) [n = 4], and CY alone (n = 1). Four deaths occurred early after transplant. There were three males and one female at median age at death of 51 years (range 24-68). The AHSCT-related deaths have been observed on days + 1, + 4, + 9, and + 15 after procedure. The causes of death included bilateral pneumonia followed by multi-organ failure in three patients and myocardial infarction in one. Three patients expired late during post-transplant follow-up, after 5, 21, and 42 months. The causes of death were disease progression in two patients and sudden heart attack in one. Eleven patients are alive after median follow-up after AHSCT of 42.0 months (range 0-95). Before proceeding to AHSCT in systemic sclerosis, there is a strong need to optimize patient selection to reduce toxicity. The administration of alemtuzumab should be avoided due to high risk of life-threatening infectious complications.