Graft-versus-host disease as an unusual complication following autologous stem cell transplantation

IntroductionGraft-versus-host disease (GVHD) is a common and serious complication after allogeneic stem cell transplantation (allo-SCT). However, a similar syndrome has been reported after autologous stem cell transplantation (ASCT) as well. Case reportA 61-year-old female diagnosed with immunoglobulin (Ig) G lambda multiple myeloma completed 10 cycles of bortezomib, thalidomide, and dexamethasone (VTD) and 2 cycles of cyclophosphamide, thalidomide, and dexamethasone (CTD). High-dose of melphalan (200 mg/kg) was given as conditioning, followed by an infusion of 2.5 × 10 CD34+ cells/kg. Three months later, she received her second ASCT. On Day +25 after tandem ASCT, the patient developed a maculopapular, itchy skin rash, which covered her face, trunk, and limbs. A skin biopsy was in line with the diagnosis of GVHD. The other organs were not involved. Treatment with systemic and local corticosteroids (CSs) resulted in the improvement of skin lesions, but the CSs were slowly tapered due to toxicity. In the following weeks, she developed symptoms of liver and gut involvement, which were resistant to steroids. The introduction of other immunosuppressive agents failed to achieve a response. As a consequence, she had cytomegalovirus (CMV) reactivation, as well as pancytopenia, and eventually, she died of infectious complications. ConclusionsGVHD after ASCT remains a rare but life-threatening complication with poor prognosis

Allogeneic stem cell transplantation remains an effective therapeutic approach for patients with therapy-related acute myeloid leukemia

Introduction: Therapy-related acute myeloid leukemia (t-AML) remains a late consequence of exposure to cytotoxic chemo- and/or radiotherapy for prior malignant or non-malignant disorders. The prognosis of t-AML is extremely poor, and allogeneic stem cell transplantation (allo-SCT) seems to be the most effective therapeutic approach.We evaluated the efficacy and safety of allo-SCT for t-AML preceded by solid tumors and lymphomas. Material and methods: Study patients were retrospectively identified using our institutional database. Nineteen patients (12 female, 7 male), median age 53 years, underwent allo-SCT for t-AML between 2006 and 2018. Results: Prior malignancy was diagnosed at median age of 43.9 years. Among 19 patients included in the study, 6 (32%) had prior breast cancer, 2 (11%) were diagnosed with papillary thyroid cancer, and 2 (11%) were treated for lymphoma. A variety of other cancers were diagnosed in the remaining 9 patients. Median time from previous malignancy to devel­opment of t-AML was 4.9 years. Fourteen patients (74%) were transplanted in first complete remission (CR1), 4 patients (21%) were in CR2, and 1 patient received graft being in active disease. 10 patients (53%) are alive at last contact in CR. Patients died mainly from infectious complications. Median follow-up from prior malignancy and from transplanta­tion was 9.5 years and 1.82 years, respectively. The 2-year overall survival (OS) was 57%. Median OS for survivors is 4.08 years. Grafts from unrelated donors and the presence of acute graft-versus-host disease affected OS. Conclusions: Allo-SCT remains an effective therapy for t-AM

Feasibility of up-front autologous stem cell transplantation for high risk diffuse large B-cell lymphoma – non-randomized analysis of 58 consecutive patients

IntroductionHigh-dose chemotherapy supported by autologous stem cell transplantation (ASCT) continues to be a standard of care for relapsed diffuse large B-cell lymphoma (DLBCL) and may be considered as a frontline consolidation for a proportion of patients with high-risk features. AimWe evaluated the feasibility and safety of ASCT for high-risk DLBCL who are in first complete remission after standard treatment with chemotherapy ± rituximab. Material and methodsA retrospective analysis of 58 patients (36 males and 22 females) receiving up-front ASCT between 1996 and 2018 for remission consolidation. ResultsOf the diagnosed, fifty patients were in clinical stage ≥ III. Forty-two (72%) of transplanted patients had age-adjusted IPI ≥ 2. The “B” symptoms were present in 34 patients. The conditioning consisted of cyclophosphamide, carmustine, etoposide (CBV) in 32 patients, carmustine, cytarabine, etoposide, melphalan (BEAM) in 18, and 8 patients received bendamustine, cytarabine, etoposide, melphalan (BeEAM). The transplant-related mortality was 0% at day +30 and +100 after ASCT. Median overall survival (OS) was 4.2 years whereas progression-free survival (PFS) reached 3.0 years. The estimated 5-year OS and PFS were found to be 66% and 64%, respectively. The presence of “B” symptoms remained significance in multivariate analysis (HR 4.17 [95% CI: 1.19–14.5]; = 0.02). No grade 3 or 4 non-hematological adverse events were observed. ConclusionsUp-front ASCT was found to be a safe and feasible procedure with long-term remission in approximately 70% of patients

The outcome of primary mediastinal B-cell lymphoma in a single center experience

IntroductionPrimary mediastinal B-cell lymphoma (PMBCL) is an aggressive distinct subtype of diffuse large B-cell lymphoma (DLBCL). There is no standard treatment for PMBCL and the value of mediastinal radiotherapy and autologous hematopoietic stem cell transplantation (AHSCT) remains to be elucidated.Material and methodsA retrospective analysis of 12 patients with PMBCL (8 male and 4 female) at median age of 36 years has been performed. Induction chemotherapy consisted of R-DA-EPOCH (n=7), R-CHOP (n=4) and R-CVP (n=1). Second and third line treatments were administered in 6 and 2 patients, respectively. Nine patients were given involved field mediastinal radiotherapy. Finally, 8 patients were proceeded to AHSCT.ResultsFour patients achieved CR and 4 PR after induction therapy with an overall response rate of 66%. In total, after completion all lines of the combined chemotherapy, the following disease responses have been observed: complete response (CR) in 4 patients, partial response (PR) in 6 and no response/disease progression (NR/PD) in 2. The overall response rate was 83%. Eight patients were proceeded to AHSCT (4 in CR and 4 in PR). The transplant-related mortality was 0% at day 100. Median follow-ups from diagnosis and from AHSCT were 39.5 months (range 8–106) and 32 months (range 3–95), respectively. All transplanted patients are alive with CR confirmed in PET scans.ConclusionsThe vast majority of PMBCL patients are susceptible to immunochemotherapy with a high response rate achieved after R-DA-EPOCH/R-CHOP regimens. AHSCT seems to be an option for fit patients with disease chemosensitivity

Multiparameter flow cytometry for assessment of minimal residual disease in patients with myelodysplastic syndromes treated with allogeneic stem cell transplantation

BackgroundMyelodysplastic syndromes (MDSs) are a heterogeneous group of clonal myeloid neoplasms. Allogeneic stem cell transplantation (allo-SCT) remains the curative method for MDS treatment. Little is known about the monitoring of minimal residual disease (MRD) in patients with MDS after allo-SCT. AimWe aimed to evaluate the significance of leukemia-associated immunophenotypes (LAIPs) identified in acute myeloid leukemia (AML) for MRD monitoring in patients with MDS after allo-SCT. Material and methodsSeven males and 4 females with a median age of 55 years were included. The diagnosis of MDS was established according to 2016 World Health Organization (WHO) criteria. The significance of eight LAIPs in bone marrow samples using multiparameter flow cytometry (MFC) was evaluated for MRD. ResultsEight patients were positive for several LAIPs before allo-SCT. The identified LAIPs included the presence of aberrant lymphoid antigens on myeloblasts and lack of CD33 expression on myeloblasts. All studied MDS patients were negative for LAIPs at Day +30 after the procedure. This was followed by full-donor chimerism in all cases. The Ogata score after allo-SCT decreased in all patients in whom it was indicative for MDS before allo-SCT. ConclusionsMFC could be useful in monitoring MRD in MDS patients after allo-SCT. Further studies in this field are needed

Pierwsza w Polsce allogeniczna transplantacja komórek macierzystych u chorego z oporną postacią białaczki włochatokomórkowej

Introduction. Hairy cell leukemia (HCL) is an uncommon B-cell lymphoproliferative disorder characterized by distinctive cells present in bone marrow, peripheral blood and spleen. Treatment of relapsed and/or refractory (R/R) HCL remains a challenge. Case report. A 28-year-old male was treated with cladribine +/- rituximab for his newly diagnosed BRAF-V600 mutated HCL. A year later leukemia relapsed and he received interferon alfa with poor response. Subsequently, vemurafenib was continued for 5 months but this treatment also failed. Then, he received bendamustine with rituximab but significant response was not achieved. Finally, he was found eligible for allogeneic stem cell transplantation (Allo-SCT) from a 9/10-matched unrelated donor. He was conditioned with total body irradiation (TBI) and cyclophosphamide. Cyclosporine and methotrexate were used as graft-versus-host prophylaxis (GVHD). He engrafted and achieved full donor chimerism. There were 0.4% of hairy cells in bone marrow sample by flow cytometry at discharge. 3 months after transplantation he developed neurological and psychiatric deficits which remained unexplained despite a detailed work-up. The symptoms partly resolved after steroids implementation. At the last contact, 14 months after transplantation he remained in complete remission and his neurological condition improved substantially. Conclusions. Allo-SCT seems to be a promising treatment option for R/R HCL.Wprowadzenie. Białaczka włochatokomórkowa (HCL) to rzadki nowotwór limfoproliferacyjny, z obecnością charakterystycznych komórek w krwi obwodowej, szpiku oraz śledzionie. Leczenie postaci nawrotowej i opornej białaczki włochatokomórkowej stanowi istotne wyzwanie. Opis przypadku. 28-letni mężczyzna otrzymał kladrybinę z rytuksymabem z powodu noworozpoznanej białaczki włochatokomórkowej z obecną mutacją BRAF-V600. Rok później z powodu nawrotu białaczki włączono interferon alfa z niewielką skutecznością. Następnie, podano wemurafenib, który chory kontynuował przez 5 miesięcy, jednak ostatecznie terapia ta również była nieskuteczna. Jako kolejna linię leczenia zastosowano bendamustynę z rytuksymabem, ponownie nie uzyskując istotnej odpowiedzi. Ostatecznie u chorego wykonano allogeniczne przeszczepienie od dawcy niespokrewnionego zgodnego w 9/10 antygenach HLA. Jako kondycjonowanie otrzymał naświetlanie całego ciała oraz cyklofosfamid. W profilaktyce choroby przeszczep przeciwko gospodarzowi podawano cyklosporynę i metotreksat. Obserwowano cechy wszczepu i chory uzyskał chimeryzm dawcy. Przy wypisie odsetek komórek włochatych w szpiku wynosił 0.4% w badaniu cytometrem przepływowym. 3 miesiące po przeszczepieniu u pacjenta zaobserwowano objawy neurologiczne i psychiatryczne, których przyczyna pozostała niejasna pomimo wytężonej diagnostyki. Objawy częściowo ustąpiły w wyniku leczenia sterydami. Obecnie 14 miesięcy po transplantacji chory pozostaje w całkowitej remisji, a obserwowane objawy neurologiczne ulegają istotnej poprawie. Wnioski. Transplantacja allogeniczna wydaje się być obiecującą opcją terapeutyczną u chorych z nawrotową i oporną białaczką włochatokomórkową

Ruxolitinib for steroid-refractory acute graft versus host disease: case series and literature review

Not require

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 posttransplant 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: 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