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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

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.

Infections are still a major reason of morbidity and one of the most common causes of death after hematopoietic cell transplantation (HCT). Antimicrobial prophylaxis plays a crucial role in decreasing non-relapse mortality after HCT. The objective of this guideline paper is presentation of current recommendations of antimicrobial prophylaxis for children and adults after hematopoietic cell transplantation, prepared in cooperation of Polish scientific hematological societies. Recommendations were prepared by the working group and finally approved by all 23 Polish transplant centers for children and adults. Existing ECIL (European Conference on Infections in Leukemia) and EBMT (European Society of Blood and Marrow Transplantation) guidelines, as well as results of survey performed among all Polish transplant centers, were the background material for working group. Recommendations are presented in sections dedicated to antibacterial prophylaxis, antifungal prophylaxis, antiviral prophylaxis, as well as prophylaxis of toxoplasmosis and infections with Pneumocystis jiroveci. Recommendations on principles of vaccination against COVID-19 are provided based on the state of knowledge in September 2021. A section on guidelines of environmental prophylaxis is also presented.

Thymus and activation-regulated chemokine (TARC) is expressed on Reed-Sternberg cells of patients with classical Hodgkin lymphoma (HL) and may serve as a marker in response assessment. In our study, we correlated serum TARC levels with early response to treatment measured by PET/CT in 19 newly diagnosed patients with HL who received ABVD (Adriblastin, Bleomycin, Vinblastine, Dacarbazine) regimen. Finally, 17 patients were analyzed and six of them (35%) achieved PET/CT negativity defined as Deauville (D) 1 or 2 after 2 cycles of ABVD; 11 pts (65%) had D3 on PET/CT. None of the patients presented D 4/5. Median serum TARC levels at diagnosis were significantly higher when compared with healthy controls: 5718 pg/ml vs 76.1 pg/ml (p p = 0.049. There was a tendency to higher baseline serum TARC levels in patients with an increased LDH (lactate dehydrogenase) activity (p = 0.08) and in those who progressed when compared with those who maintained response (p = 0.09). Serum TARC levels decrease after chemotherapy and may serve as a marker of response assessment.

Ruxolitinib is widely used in myelofibrosis (MF). However, some patients do not optimally respond and require more efficacious treatment. Our analysis aimed to establish predictors of ruxolitinib response.We designed a multicenter, retrospective analysis of the efficacy of ruxolitinib treatment in patients with MF in 15 Polish hematology centers. As responses to ruxolitinib occur within the first 6 months, we used this point to evaluate the efficacy of treatment. Symptoms response was defined as ≥50% reduction of the MF constitutional symptoms assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Spleen response was defined as ≥50% reduction of the difference between the spleen's baseline length and the upper limit norm measured by ultrasonography.320 MF patients were enrolled. At 6 months of therapy, the spleen response was detected in 140 (50%) patients, and symptoms response in 241 patients (76%). Multivariable analysis identified leukocytosis25 G/L (OR 2.06, 95%CI: 1.12-3.88, P = .0200), and reticulin fibrosis MF 1 (OR 2.22, 95%CI: 1.11-4.46, P = .0249) contributed to better spleen response. The time interval between MF diagnosis and ruxolitinib administration shorter than 3 months, and platelets ≥150 G/L (OR 1.69, 95% CI 1.01-2.83, P = .0466) influenced symptoms response.Establishing predictive factors for ruxolitinib response is particularly important given the potential for new therapies in MF. In patients with a low likelihood of responding to ruxolitinib, using other JAK inhibitors or adding a drug with a different mechanism of action to ruxolitinib may be of clinical benefit.

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-AML

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.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 (blasts5% in BM).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.

The number of newly diagnosed haematological malignancies in Polish adults and children is about 9,000 a year, which constitutes about 5.5% of all malignancies in the country. Adult patients with haematological malignancies are diagnosed and treated in 42 institutions in Poland. The scientific and educational support for this activity is provided under the umbrella of the Polish Society of Haematologists and Transfusiologists (PTHiT, Polskie Towarzystwo Hematologow i Transfuzjologow ), the Polish Adult Leukemia Group (PALG), the Polish Lymphoma Research Group (PLRG), the Polish Myeloma Study Group (PMSG), the Polish Myeloma Consortium (PMC), and consultants in haematology. The aim of this position paper is to present the current status and progress in therapy of haematological malignancies in Polish haematology adult centres, focusing on the activity of PALG, PLRG, and PMSG. The achievements of Polish haemato-oncology at the beginning of the third decade of the 21 st century are set out in this paper. Polish haemato-oncology today has an important international position based on contributions to the development of knowledge, international cooperation, and a high quality of patient care. In many instances, clinical trials run by Polish collaborative groups have influenced international standards. Polish haematologists have been the authors of treatment recommendations, and their research has indicated areas for further research.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) remains a valuable therapeutic approach for relapsed and refractory (R/R) patients with diffuse large B-cell lymphoma (DLBCL). The aim of the study was to evaluate the safety and clinical outcome of ASCT for R/R DLBCL. We present a retrospective series of ASCT for 53 DLBCL patients (30 males and 23 females) at the median age of 51 years. Patients were eligible for transplantation if they achieved partial, second, or subsequent response or remained stable to at least 2 prior treatments. Median overall (OS) and progression-free (PFS) survivals were 9 and 6.3 years, respectively. The estimated 4-year OS and PFS were found to be 75% and 69%, respectively. In univariate analysis liver involvement, clinical stage at diagnosis, lymphocyte/monocyte count, and status of clinical response at ASCT were found to influence OS, however, only absolute lymphocyte count remained significant in multivariate analysis (HR 1.42 [95% CI: 1.08-1.87]; p=0.01). Median follow-up from ASCT to the last contact was 4.4 years (range 0.03-18.7). In total, 26 patients died from disease progression and subsequent resistance to chemotherapy. At the last contact, 27 patients were alive in remission. Only a single patient died shortly after ASCT due to infectious complications. Grade 3 or 4 non-hematological side effects were not observed in the remaining patients. ASCT for RR DLBCL is a safe procedure with a high probability of overall and progression-free survival.

Systemic mastocytosis (SM) is a rare hematological malignancy characterized by an abnormal expansion and accumulation of pathological mast cells in bone marrow and other organs including skin, liver, spleen and lymph nodes. The clinical manifestation can be extremely heterogeneous, from limited skin changes to multi-organ involvement or mast cell tumors. The median survival of patients diagnosed with indolent form is comparable to healthy population, while prognosis for patients with advanced disease is poor, with an estimated survival ranging from several months to several years. In most patients (> 90%), a somatic mutation in codon 816 of the c-KIT gene encoding tyrosine kinase receptor is detected. Additional molecular abnormalities and even coexistence of other hematological cancers, e.g . acute leukemia, are also observed. Regardless of the form of disease or serum tryptase concentration, patients are exposed to symptoms resulting from the release of mast cell mediators — most often itching, paroxysmal redness and blisters, and general mediator-induced symptoms — such as nausea, vomiting, diarrhea, abdominal pain, hypotensive episodes, fatigue, headache, fever, shortness of breath, osteopenia, osteoporosis and severe anaphylactic reactions. This paper presents current outlook on the diagnostic and treatment process of SM, taking into account the interdisciplinary aspects of the disease.

Purpose In this multicenter retrospective analysis of the Polish Myeloma Group we assessed the real-life application of allogeneic transplantations (alloHCT) in multiple myeloma (MM) outside clinical trials in Poland. Methods Anonymized clinical data of patients who underwent alloHCT were retrospectively collected from eight transplant centers and analyzed to identify factors affecting the outcome. Results Sixty patients (34 males, 26 females) at median age of 45 (22–59) years who received alloHCT between 1993 and 2016 were included. In this group, 16 (27%) patients underwent myeloablative conditioning and 44 (73%) reduced-intensity conditioning alloHCT. Acute graft versus host disease (GvHD) occurred in 27 (45%) patients, while chronic GvHD was diagnosed in 13 (22%) patients. With the median observation time after alloHCT of 10 months, the relapse rate was 38%. Median progression-free survival (PFS) reached 9 months (0–183) while median overall survival (OS) was 23 months (0–183). Main causes of death included disease progression in 16 (43%), infections in 10 (27%), and GvHD in 7 patients (19%). Presence of chronic GvHD was the only factor associated with prolonged PFS (28 vs. 6 months; p = 0.05), however its impact on OS was not statistically significant (73 vs. 8 months; p = 0.09). Conclusions In this relatively small and heterogeneous study we observed that alloHCT was associated with high risk of severe complications, but resulted in long-term survival in a proportion of patients. Decisions on optimal indications and timing of the alloHCT in MM need to be taken in the broader context of reported outcomes including data from large studies.

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.

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.

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 = p

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) 9/l (n = 1) and/or hemoglobin level n = 4) and/or platelet count 9/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.

IntroductionSystemic mastocytosis (SM) with an associated hematological neoplasm (SM-AHN) constitutes about 40% of all patients with SM. AHN commonly includes myeloid neoplasms and chronic myelomonocytic leukemia (CMML) is seen in about 30% of these patients.Case reportA 67-year-old male presented to hematologist with fatigue and significant weight loss. Abdominal ultrasound and computed tomography (CT) detected hepatosplenomegaly, abdominal lymphadenopathy, and ascites. He was anemic with leukocytosis and eosinophilia. Trephine biopsy showed > 30% of spindle-shaped mast cells. The KITD816V mutation was present. Serum tryptase level was elevated to 62 ng/mL. The patient was diagnosed with aggressive SM and received six cycles of cladribine with partial response. Three years later, he developed severe anemia. Eosinophilia and monocytosis (5.6 × 109/L) were demonstrated in blood film. Hepatosplenomegaly and abdominal lymphadenopathy were also present. Trephine biopsy did not demonstrate the presence of spindle-shaped mast cells, but dysplasia in erythroid and myeloid lineages was evident. The histological result of lymph node biopsy as well as blood and bone marrow findings were in line with CMML. He received hydroxyurea, but he transformed soon into fatal acute monocytic leukemia.ConclusionsThe prognosis of SM-AHN depends on AHN component. Leukemic transformation of AHN component may occur in a proportion of patients.

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 × 106 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.

Bing-Neel syndrome (BNS) is a rare presentation of Waldenström macroglobulinemia (WM). BNS is a consequence of the central nervous system (CNS) involvement by lymphoplasmacytic lymphoma (LPL) and, rarely, the peripheral nervous system. The data on BNS are extremely scarce. Therefore, we performed a multicenter retrospective analysis of BNS patients diagnosed and treated in centers aligned with the Polish Lymphoma Research Group. The analysis covers the years 2014–2021. Eleven patients were included, 55% females and the median age at BNS diagnosis was 61 years. The median time from WM to BNS was 3.5 years; 27% of patients did have a diagnosis of WM and BNS made simultaneously or within 30 days from each other. Isolated parenchymal involvement was the least frequent (20%). Patients were treated with different regimens, mostly able to cross the blood-brain barrier, including 18% treated with ibrutinib first line. The cumulative objective response to treatment was 73%. With the median follow-up of 20 months (95% CI, 2–32), the 36-month estimates were: overall survival (OS) 47%, progression-free survival (PFS) 33%, and cumulative incidence of BNS-associated death 41%. The performance status according to ECOG was significant for PFS (HR = 7.79) and the hemoglobin concentration below 11 g/dL was correlated with PFS. To conclude, BNS is a very rare manifestation of WM. It is associated with a poor outcome with most patients succumbing to BNS.

Michał Janowski,1,* Zofia Ulańczyk,2,* Karolina Łuczkowska,2 Anna Sobuś,2 Dorota Rogińska,2 Ewa Pius-Sadowska,2 Michał Gniot,3 Krzysztof Kozłowski,4 Krzysztof Lewandowski,3 Grzegorz Helbig,5 Bogusław Machaliński,2 Edyta Paczkowska2 1Department of Hematology and Transplantology, Pomeranian Medical University, Szczecin, Poland; 2Department of General Pathology, Pomeranian Medical University, Szczecin, Poland; 3Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznań, Poland; 4Department of Constitutional Law, Faculty of Law and Administration, Jagiellonian University in Krakow, Krakow, Poland; 5Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland*These authors contributed equally to this workCorrespondence: Edyta Paczkowska, Email edyta.paczkowska@pum.edu.plIntroduction: The aim of our research was to investigate changes in the molecular background of the immune response in the chronic phase (CP) of chronic myeloid leukaemia (CML) during treatment with tyrosine kinase inhibitors (TKIs).Methods: Global gene and miRNA expression profiles were assessed using genome-wide RNA and miRNA microarray technology in bone marrow mononuclear cells. Fifty-one patients were recruited, and bone marrow samples were taken at diagnosis before treatment with TKIs and after 3, 6, and 12 months of treatment with TKIs. The largest number of upregulated genes was observed when the 0-month group (time of diagnosis) was compared to the 3-month group; 1774 genes were significantly upregulated, and 390 genes were significantly downregulated.Discussion: Upregulated biological processes according to gene ontology (GO) classification involved basic cellular processes such as cell division, cell cycle, cell–cell adhesion, protein transport, mitotic nuclear division, apoptosis, and DNA replication. Differentially expressed miRNAs were annotated using GO classification to several immunity-related processes, including the T cell receptor signalling pathway, T cell costimulation, immune response, and inflammatory response. TKI therapy exerts a significant impact on cellular cycle processes and T-cell activation, which was proven at the molecular level.Keywords: chronic myeloid leukaemia, tyrosine kinase inhibitor, immune response, gene microarrays, miRNAs

Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease.We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response.A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy.Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.).