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.

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.

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.

Differential Function of a Novel Population of the CD19+CD24hiCD38hi Bregs in Psoriasis and Multiple Myeloma.

Psoriasis (Ps), an autoimmune disease, and multiple myeloma (MM), a blood neoplasm, are characterized by immune dysregulation resulting from the imbalance between the effector and regulatory cells, including B regulatory (Breg) lymphocytes. Peripheral blood samples from 80 Ps patients, 17 relapsed/refractory MM patients before and after daratumumab (anti-CD38 monoclonal antibody) treatment, 23 healthy volunteers (HVs), and bone marrow samples from 59 MM patients were used in the study. Bregs were determined by flow cytometry using CD19, CD24, and CD38. Intracellular production of interleukin-10 (IL-10) was assessed by flow cytometry after CD40L, LPS, and CpG stimulation. IL-10 serum or plasma concentrations were tested using ELISA method. The percentage of CD19+CD24hiCD38hi Bregs was not different whereas the production of IL-10 in Bregs was significantly higher in Ps patients in comparison with HVs. The percentage of CD19+CD24hiCD38hi Bregs in MM patients was significantly higher than in HVs (p < 0.0001). The percentage of CD19+CD24hiCD38hi Bregs was significantly higher in MM patients with the ISS stage I (p = 0.0233) while IL-10 production in Bregs was significantly higher in ISS stage III (p = 0.0165). IL-10 serum or plasma concentration was significantly higher in Ps and MM patients when compared to HVs (p < 0.0001). Following the treatment with daratumumab the percentages of CD19+CD24hiCD38hi Bregs significantly decreased (p < 0.0003). Here, in the two opposite immune conditions, despite the differences in percentages of Bregs in Ps and MM we have identified some similarities in the IL-10 producing Bregs. Effective treatment of daratumumab besides the anti-myeloma effect was accompanied by the eradication of Bregs.

Efficacy of daratumumab monotherapy in real-world heavily pretreated patients with relapsed or refractory multiple myeloma.

PURPOSE: Daratumumab is a promising new agent for relapsed/refractory multiple myeloma (RRMM). However, there are limited data on its clinical activity and tolerability in the real-world patients. The purpose of this study is to determine the efficacy and toxicity profile of daratumumab monotherapy in the real-life setting. PATIENTS AND METHODS: Thirty RRMM patients treated with daratumumab who had previously received at least three treatment lines including a proteasome inhibitor and an immunomodulatory drug or had been double refractory (DRMM) were included to the Polish Myeloma Group observational study. RESULTS: The objective response rate to daratumumab was 42.8%. Median progression-free survival (PFS) and overall survival reached 9.5 and 13.8 months, respectively. Importantly, patients with DR-MM had a significantly shorter PFS than other patients (median PFS of 4.1 vs. 12.1 months). Daratumumab was generally well tolerated, however two patients had their therapy interrupted due to adverse events. CONCLUSION: Daratumumab monotherapy has significant activity and good tolerance in heavily pretreated RRMM patients.

[An attempt to assess women's knowledge about caesarean section in the questionnaire survey].

OBJECTIVE: Introduction: In last year the proportion of caesarean sections constantly growing. The aim: To evaluate the knowledge in the questionnaire survey of women about the Caesarean section. PATIENTS AND METHODS: Materials and methods: 1462 women in age 18-57 were tested by the method of diagnostic survey. The tool of research was own survey composed of 26 question. RESULTS: Results: Among 1462 of women, which was poll, 79,6% described anxiety as the main factor to make a decision to have a caesarean section. The most frequently mentioned disease in 93,6%, which may appear among women after surgery were adhesions, while a delay of lactation in 59,36% has a negative influence on newborn children. CONCLUSION: Conclusions: 1. The percentage increase of elective caesarean sections is related to the extension of procedures related to psychiatric indications. However, most women, still prefer a natural birth because of safety for the mother and the child. 2. The awareness of women with higher education causes a higher percentage of cesarian sections, because of the greater anxiety about their own health, health of the newborn and safety of a natural birth. 3. Women in a reproductive age should have access to literature and antenatal schools, but also to psychoeducational meetings and a detailed discussion on this subject of both forms of delivery. 4. Increasing the number of cesarean sections to avoid criminal, civil and professional liability contributes to the increase of awareness and claims and by the knowledge of the law by the society.

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.

Selected psychological aspects of functioning of a patient after repeated miscarriages − case study

The purpose of our case study was to identify psychological and medical dependencies affecting subsequent pregnancies of women after early pregnancy loss. The patient miscarried three times, gave birth to two children. The case study describes her state of health, emotional reactions and social support in these situations. Based on medical information, psychological interview and questionnaires (STAI, CISS, BHI-R, ISEL) are described factors influencing the patient's coping with such a difficult situation as the loss of pregnancy.

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.

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.

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.

Treating oral mucositis with a supersaturated calcium phosphate rinse: comparison with control in patients undergoing allogeneic hematopoietic stem cell transplantation.

PURPOSE: Of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), 75% or more experience oral mucositis, a painful acute complication that can delay discharge, interrupt treatment, and threaten life. To evaluate the efficacy of a supersaturated calcium phosphate rinse (SCPR), we compared it with customary care--topical mouth solutions--on measures of severity and consequent interventions and complications. METHODS: In this randomized controlled trial, 40 patients undergoing allogeneic HSCT were randomized: 20 to SCPR four times daily and 20 to solutions made with salvia leaf extract, iodine-povidine, and fluconazole. Treatment extended from initiation of conditioning treatment until the granulocyte count was ≥0.2 g/L. Mucositis severity was measured daily by a hematologist according to a World Health Organization (WHO) scale and self-assessed by patients. Need for interventions [analgesics, total parenteral nutrition (TPN), and granulocyte colony-stimulating factor] and complications (acute graft-versus-host disease and infections) were also assessed. RESULTS: In comparison with the control group, the SCPR group had significantly lower mean measures of WHO oral toxicity (0.9 vs. 1.8; P = 0.02), disease course (3.2 vs. 7.1 days; P = 0.02), and peak mouth pain (0.85 vs. 1.75; P = 0.005). Analgesic need was significantly shorter (1.1 vs. 3.4 days; P = 0.047) and the need for TPN significantly lower (0 vs. 6 patients; P = 0.02; 0 vs. 1.9 mean days; P = 0.009). Measures of complications were lower in the SCPR group, but not significantly so. Trial limitations include the impracticality of achieving double blinding with agents so different in appearance and in preadministration preparation. CONCLUSIONS: Compared with the control group, the SCPR group had significantly lower mean measures of oral toxicity, peak mouth pain, and disease course duration. These results warrant confirmation in controlled, multicenter, randomized trials.

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.

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-beta1) 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-beta1. TGF-beta1 serum concentration was assessed using a commercial ELISA. RESULTS: In all patients, a prompt decrease in TGF-beta1 mRNA expression and its serum concentration was demonstrated after conditioning. In patients with acute GVHD, TGF-beta1 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-beta1 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-beta1 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-beta1 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-beta1 in graft-versus-host disease pathophysiology.

Hematopoietic stem cell mobilization with the reversible CXCR4 receptor inhibitor plerixafor (AMD3100)-Polish compassionate use experience.

Recent developments in the field of targeted therapy have led to the discovery of a new drug, plerixafor, that is a specific inhibitor of the CXCR4 receptor. Plerixafor acts in concert with granulocyte colony-stimulating factor (G-CSF) to increase the number of stem cells circulating in the peripheral blood (PB). Therefore, it has been applied in the field of hematopoietic stem cell mobilization. We analyzed retrospectively data regarding stem cell mobilization with plerixafor in a cohort of 61 patients suffering from multiple myeloma (N = 23), non-Hodgkin's lymphoma (N = 20), or Hodgkin's lymphoma (N = 18). At least one previous mobilization attempt had failed in 83.6% of these patients, whereas 16.4% were predicted to be poor mobilizers. The median number of CD34+ cells in the PB after the first administration of plerixafor was 22/µL (range of 0-121). In total, 85.2% of the patients proceeded to cell collection, and a median of two (range of 0-4) aphereses were performed. A minimum of 2.0 × 10(6) CD34+ cells per kilogram of the patient's body weight (cells/kg b.w.) was collected from 65.6% of patients, and the median number of cells collected was 2.67 × 10(6) CD34+ cells/kg b.w. (0-8.0). Of the patients, 55.7% had already undergone autologous stem cell transplantation, and the median time to neutrophil and platelet reconstitution was 12 and 14 days, respectively. Cases of late graft failure were not observed. We identified the diagnosis of non-Hodgkin's lymphoma and previous radiotherapy as independent factors that contributed to failure of mobilization. The current report demonstrates the satisfactory efficacy of plerixafor plus G-CSF for stem cell mobilization in heavily pre-treated poor or predicted poor mobilizers.