BACKGROUND:Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a rare but highly fatal complication after allogeneic hematopoietic cell transplantation (allo-HCT), frequently diagnosed under conditions of clinical uncertainty. We aimed to characterize post-transplant sHLH/MAS and to identify clinically accessible factors associated with early mortality. METHODS:We retrospectively analyzed adult patients who developed sHLH/MAS after allo-HCT between 2018 and 2025. Inclusion required an HScore ≥ 169. Overall survival within 60 days from sHLH/MAS onset was the primary endpoint. Clinical and laboratory variables were evaluated using Cox proportional-hazards models, and patients were stratified according to the number of adverse prognostic factors identified. RESULTS:Seventy-two patients met inclusion criteria. Median time from allo-HCT to sHLH/MAS onset was 22 days. Sixty-day overall survival was poor. In univariable and multivariable analyses, vasopressor-dependent sepsis (HR 7.77, p < 0.001) and ferritin > 15 000 μg/L (HR 3.48, p = 0.002) were independently associated with early mortality. Stratification based on these two factors separated patients into low-, intermediate-, and high-risk groups with 60-day survival of 92%, 52%, and 9%, respectively (p < 0.001). CONCLUSIONS:Post-transplant sHLH/MAS is associated with extremely high early mortality. Vasopressor-dependent sepsis and extreme hyperferritinemia identify patients at particularly high risk. These findings require confirmation in independent cohorts.

The introduction of the complement component C5 inhibitor eculizumab has radically changed the prognosis and quality of life of patients with paroxysmal nocturnal hemoglobinuria. Up to 30 % of patients develop only a suboptimal response to C5 inhibition. One reason for this is activation of extravascular hemolysis, due to opsonization of erythrocytes with fragments of the C3 component. Pegcetacoplan, the first ever registered C3 inhibitor, is aimed at solving this problem.In Russia, 2 patients received pegcetacoplan as part of a phase 3, randomized, open-label, active-comparator controlled trial PEGASUS. The analysis includes data from the first year of therapy: the run-in period (pegcetacoplan 1080 mg SC twice weekly in addition to the current dose of eculizumab, 4 weeks), the randomized controlled period (both patients were randomized to eculizumab monotherapy, 16 weeks), and the open-label period of pegcetacoplan therapy (32 weeks). Data from the extension study to evaluate the long-term safety and efficacy of pegcetacoplan are also presented. The duration of follow-up on pegcetacoplan therapy in both patients exceeded 4 years.

We have evaluated clinical outcomes in 49 patients who received unmanipulated allogeneic hematopoietic stem cell transplantation (allo-HSCT) as a salvage treatment for primary (PGF) and secondary graft failure (SGF).The median age of patients was 31 years.Indications for the first allo-HSCT were malignant (n=43, 88%) and nonmalignant diseases (n=6, 12%).Thirteen patients with malignant diseases (27%) were in the active phase of disease.Patients with PGF received a second graft, at a median interval of 43 days (34-82) after allo-HSCT.The second allo-HSCT (HSCT2) were performed from haploidentical (n=42, 86%), HLA-matched related (n=2, 4%) and unrelated (n=5, 10%) donors.Donor-specific antibodies (DSA) before the 1 st allo-HSCT (HSCT1) were examined in 21 cases, and detected in 7 patients.Donor change in 2 nd HSCT was performed in 23 cases.Following HSCT2, the neutrophil counts exceeding 0.5×10 9 /L were achieved in 21(43%) patients with a cumulative incidence (CI) of 33% (95% CI, 19-48) and median engraftment time of 29 (1-41) days; blood platelet counts over 50×10 9 /L were achieved in 11(22%) patients.The 3 rd allo-HSCT was required in 14 patients.A total of 34 patients died, the cause of death in 31 cases was infection, in three cases -relapse of the underlying disease.The one-year relapse-free survival rate after HSCT2 was 65% (95% CI 51-79), the one-year event-free survival rate) was 20% (95%CI, 11-37) with relapce, acute graft-versus-host disease (aGvHD) grade 3-4 considered as event.One-year overall survival (OS) was 33% (95% CI, 22-50), 5 year OS was 28% (95% CI, 18-45).Source of the graft was the only factor which showed an association with OS: usage of peripheral blood stem cells (50%; 95%, CI 31-66) versus bone marrow (26%; 95% CI 2-65, p=0.049).

The article contains a short overview of reports and poster communications

Asciminib is a novel BCR::ABL1inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP) showing effectiveness and good safety profile according to the results of a phase I and III studies in patients with Ph-positive chronic myeloid leukemia (CML) failing prior tyrosine kinase inhibitors (TKIs).Pre-transplant use of 2 nd generation TKIs (nilotinib/dasatinib) does not change the risk of complications associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT).However, there are no appropriate data for the patients who received asciminib prior to transplant.In Russia, asciminib is available under the Managed Access Program (MAP) approved by Novartis.In the MAP program 68 patients with CML were enrolled.We reviewed data of 12 patients across 2 contributing centers, who underwent allo-HSCT between August 2021 and August 2022.Our aim was to evaluate the safety and effectiveness of preand post-transplant asciminib in allo-HSCT candidates.The median duration of asciminib before allo-HSCT was 194 days (61-377 days).92% of patients did not develop adverse events (AEs) of any grade.Median day of engraftment was D+20 (range 18-24).The 1-year overall survival was 70%.The cumulative incidence of acute GvHD (grade 1-3 until D+100) was 18%.Non-relapse mortality was 18% at 12 months.Eight patients (67%) are alive with median follow-up after allo-HSCT of 135 days and achieved deep molecular response.In our observation (limited with small dataset) asciminib was effective as a bridge therapy before allo-HSCT in highly pretreated patients with low rate of severe toxicity and acceptable rate of aGvHD.

Allogeneic stem cell transplantation (allo-HSCT) is used worldwide for long-term management and cure of hematological malignancies, still remaining a valuable option for treatment of chronic myeloid leukemia (CML) in all fit patients who are unable to achieve a durable complete cytogenetic response after treatment with tyrosine kinase inhibitors (TKIs), and in advanced-phase disease.Along with relapse risk, the unfavorable HSCT results may be associated with primary graft failure (PrGF), or poor graft function (PoGF).Hence, the aim of our study was to assess frequency and outcome of PrGF and severe poor graft function (sPGF) after allo-HSCT in CML patients. Patients and methodsWe performed a retrospective analysis of 121 consecutive patients with CML who received allo-HSCT in the RM Gorbacheva Research Institute at the Pavlov University over 25 years.HSCT was indicated in cases of advanced-phase disease, or TKI resistance/intolerance of CML patients.BCR/ABL transcript levels and additional chromosomal abnormalities were used as laboratory markers of advanced disease.80 patients (66%) were transplanted in chronic phase (CP); 41 patients (34%) were in acceleration phase (AP), or blast crisis (BC) at the time of HSCT.Matched unrelated donors were used in 65% of the cases; matched related donors, in 28%, and haploidentical donors, in 7% of cases. ResultsEngraftment was documented in 106 (88%) patients.Post-transplant relapses were registered in 31 patients within 15-333 days after HSCT.PrGF was documented in 8 cases (7%).Two patients developed secondary graft failure within two months after initial engraftment, with lethal infectious complications.Severe poor graft function (PoGF) was diagnosed in 11 cases (9%) at cumulative incidence of 10% within 1 year post-transplant.Among various pre-transplant characteristics, age factor, and, especially, presence of additional chromosomal abnormalities (ACA) were associated with cumulative incidence of PrGF and sPGF after HSCT.I.e., PrGF was 14% in the group with detectable ACA versus 3% in the group without ACA, (p=0.02),whereas incidence of sPGF in patients with ACA was 2% versus 12% in those without ACA (p=0.09).The incidence of post-transplant relapses did not differ in the patients with PrGF and sPGF.

Aim. To comparatively analyze myelofibrosis treatment outcomes with the use of ruxolitinib versus ruxolitinib with subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT) as well as to assess the efficacy of ruxolitinib in pre- and post-transplantation periods. Materials & Methods. The study enrolled 78 myelofibrosis patients who were referred to the RM Gorbacheva Scientific Research Institute to determine the indications for allo-HSCT. Allo-HSCT was performed in 33 patients, among them 32 patients with ruxolitinib pre-conditioning (ruxolitinib + allo-HSCT group). They received reduced intensity conditioning (fludarabine 180 mg/m2 and busulfan 10 mg/kg). Graft-versus-host disease (GVHD) prophylaxis included cyclophosphamide 50 mg/kg on Day +3 and Day +4, ruxolitinib 10 mg per day from Day +5 to Day +100 (n = 31), rabbit antithymocyte globulin, tacrolimus, and mycophenolate mofetil (n = 2). Ruxolitinib without allo-HSCT was administered to 45 patients (ruxolitinib group). Between the groups there were no significant differences with respect to gender, age, diagnosis, and molecular genetic variant. Results. Median therapy duration in ruxolitinib group was 16 months (range 2-78 months). In 2 (4 %) patients partial response was achieved, 8 (20 %) patients showed clinical improvement, in 16 (39 %) patients stable disease (SD) was reported, in 15 (37 %) patients disease progression (DP) was detected. The treatment succeeded in reducing the spleen size in 8 (20 %) patients and in relieving disease symptoms in 16 (39 %) patients. Cumulative incidence of progression within 3 years was 44 % (95% confidence interval [95% CI] 27-60 %). In ruxolitinib + allo-HSCT group median ruxolitinib therapy duration was 7 months (range 3-22 months). As a result, clinical improvement in 9 (28 %) cases, SD in 17 cases (53 %), and DP in 6 (19 %) cases were observed. In 5 (20 %) patients acute GVHD of grade 2-4, in 3 (12 %) patients acute GVHD of grade 3-4, and in 6 (24 %) patients chronic medium severity GVHD were identified. Within 1 year nonrelapse mortality was 28 % (95% CI 14-44 %). The 3-year cumulative incidence of relapse was 12 % (95% CI 3-28 %) in ruxolitinib + allo-HSCT group. According to the landmark analysis performed throughout 6 months from the first visit to the center, the 3-year overall survival in the group with allo-HSCT was 80 %, whereas in ruxolitinib group it was 41 % (p = 0.022), 12-month landmark analysis resulted in 77 % and 43 % (p = 0.028), and 18-month landmark analysis showed 86 % and 46 % (p = 0.015) in two groups, respectively. Conclusion. Despite the efficacy of JAK1/2 inhibitor ruxolitinib, the risk of myelofibrosis progression is not to be underestimated. Therefore, in DIPSS intermediate-2 and high-risk patients the issue about performing allo-HSCT should be promptly clarified.

cttjournal.com 60 CTT JOURNAL | VOLUME 10 | NUMBER 2 | jULy-AUgUst 2021 Alexey Yu. Polushin 1, Ksenia S. Afanasyeva 1, Bella I. Ayubova 1, Sergey N. Bardakov 2, Dmitry I. Skulyabin 2, Andrey O. Agafonov 1, Olga V. Sergiyenya 3, Yaroslav B. Skiba 1, Vladimir S. Krasnov 1, Мikhail М. Кanunnikov 1, Тatiana А. Rudakova 1, Anna G. Smirnova 1, Sergey N. Bondarenko 1, Maria D. Vladovskaya 1, Ivan S. Moiseev 1, Alexander D. Kulagin 1 1 Pavlov University, St. Petersburg, Russia 2 S. M. Kirov Military Medical Academy, St. Petersburg, Russia 3 V. A. Almazov National Medical Research Center, St. Petersburg, Russia Differential diagnosis of myelopathy in a patient with relapsed acute lymphoblastic leukemia Cellular Therapy and Transplantation (CTT). Vol. 10, No. 2, 2021 doi: 10.18620/ctt-1866-8836-2021-10-2-60-68 Submitted: 23 June 2021, accepted: 30 July 2021

Acute and chronic steroid-refractory graft-versus-host disease (srGVHD) is a life-threatening complication of allogeneic stem cell transplantation. There are a number of reports on case series describing efficacy of ruxolitinib in both acute and chronic srGVHD. We conducted a prospective study (NCT02997280) in 75 patients with srGVHD (32 acute, 43 chronic, 41 adults, and 34 children). Patients with chronic GVHD had severe disease in 83% of cases, and acute GVHD patients had grade III–IV disease in 66% of cases. The overall response rate (ORR) was 75% (95% CI 57–89%) in acute GVHD and 81% (95% CI 67–92%) in chronic. Overall survival was 59% (95% CI 49–74%) in acute group and 85% (95% CI 70–93%). The major risk factors for lower survival were grade III–IV gastrointestinal involvement (29% vs 93%, p = 0.0001) in acute form and high disease risk score in chronic (65% vs 90%, p = 0.038). Toxicity was predominantly hematologic with 79% and 44% of grade III–IV neutropenia in acute and chronic groups, respectively. There was no difference between adults and children in terms of ORR (p = 0.31, p = 0.35), survival (p = 0.44, p = 0.12) and toxicity (p > 0.93). The study demonstrated that ruxolitinib is an effective option in acute and chronic srGVHD and can be used both in adults and children.

Allogeneic HSCT (allo-HSCT) is potentially curative option for a wide variety of malignant and nonmalignant disorders of hematopoiesis.For patients who lack an HLA-matched sibling, HLA-haploidentical related donors (haplo-HSCT) can be considered as alternative sources of donor graft s.Th e benefi ts of haplo-HSCT include immediate donor availability for patients who are in urgent need of the transplant.Besides, an availability of a related donor makes post-transplant donor-derived cellular therapy more easily accessible.In addition, the greater HLA mismatch associated with haploidentical HSCT (haplo-HSCT) may potentiate graft -versus-tumor (GVT) eff ects.Th e aim of our study was to summarize our single-center experience of haplo-HSCT performed with non-manipulated graft s in adult patients with different malignant diseases.Th e study included a total of 119 patients with diff erent hematological disorders subjected to haplo-HSCT.At the time of analysis, median follow-up was 371 days (1-2219).Most frequent diagnosis in transplanted patients was acute leukemia.67 (56%) patients received haplo-HSCT as salvage therapy.Overall survival with an observation term of 2 years was 40.3% for the general group.In particular, the two-year OS in patients transplanted in remissions of ALL and AML was 57% and 46% respectively as compared to 22% and 15% for the patients transplanted in adverse disease status).Two-year event-free survival (EFS) and GVHD-free/relapse-free survival (GRFS) group proved to be 35.7% and 21% respectively.Th e cumulative incidence of acute GVHD grade II-IV and severe aGVHD grade III-IV was 19% and 10% respectively.Th e cumulative incidence of chronic GVHD (cGVHD) was 16%.Th e cumulative incidence of relapse was 21%.Th e overall transplant-associated mortality was 43% in the studied group.In conclusion, our results show that unmanipulated haplo-HSCT is reasonable treatment option for adult patients with diff erent malignant disorders of hematopoiesis.However, such problems as higher rate graft failure, increased nonrelapse mortality (NRM) and post-transplant relapses remain extremely relevant.