Before the COVID‐19 pandemic, common community‐acquired seasonal respiratory viruses (CARVs) were a significant threat to the health and well‐being of allogeneic hematopoietic cell transplant ...(allo‐HCT) recipients, often resulting in severe illness and even death. The pandemic has further highlighted the significant risk that immunosuppressed patients, including allo‐HCT recipients, face when infected with SARS‐CoV‐2. As preventive transmission measures are relaxed and CARVs circulate again among the community, including in allo‐HSCT recipients, it is crucial to understand the current state of knowledge, gaps, and recent advances regarding CARV infection in allo‐HCT recipients. Urgent research is needed to identify seasonal respiratory viruses as potential drivers for future pandemics.
Background and Objectives
Autologous stem cell transplant (ASCT) is a widely used therapy for lymphoma patients and can nowadays be performed on an outpatient basis. This study aimed to describe ...transfusion support in lymphoma patients undergoing ASCT and identify increased or prolonged transfusion requirement predictors.
Materials and Methods
A retrospective study of all consecutive lymphoma patients undergoing ASCT between 2010 and 2020.
Results
Out of 226 patients, 145 (64%) received red blood cell (RBC) transfusions, whereas all 226 (100%) required platelet transfusion (PT). Transfusions between Day +1 and +30 were higher in patients over 60 (2 1–4 vs. 2 0–2 RBC; p = 0.001 and 4 2–8 vs. 3 2–4 PT; p < 0.001); patients with pre‐transplant anaemia (4 2.5–6 vs. 2 0–2 RBC; p < 0.001 and 5 3–9 vs. 3 2–4 PT; p = 0.001); pre‐transplant thrombocytopenia (2 1–4 vs. 2 0–2 RBC; p < 0.001 and 4 3–8.5 vs. 2 1–3 PT; p < 0.001) or CD34+ cell dose <4 × 106/kg (2 0–4 vs. 2 0–2 RBC; p = 0.024 and 4 2–6 vs. 2 1–3.5 PT; p < 0.001). RBC transfusion independence was reached later in patients receiving carmustine, cytarabine, etoposide and melphalan (BEAM) (hazard ratio HR 1.6; confidence interval CI 1.1–2.3) and those requiring RBC before infusion and/or with pre‐transplant anaemia (HR 2.2; CI 1.4–3.4). Age above 60 (HR 1.4; CI 1.0–1.9), BEAM conditioning (HR 1.4; CI 1.0–2.0) and pre‐transplant thrombocytopenia and/or requiring PT before infusion (HR 1.8; CI 1.4–2.5) entailed longer time until PT independence.
Conclusion
These four factors (age ≥60 years; BEAM conditioning, CD34+ dose <4 × 106/kg and pre‐transplant cytopenia and/or Day −10 to 0 transfusion) allowed dividing patients into three groups with significant differences between them regarding the time until transfusion independence.
Background
Disease recurrence occurs in 20% to 40% of adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) who are treated with chemotherapy and tyrosine kinase ...inhibitors (TKIs). In the current study, the authors report the incidence, treatment, and outcome after first disease recurrence in young and older adults treated in the ALL Ph08 trial (ClinicalTrials.gov identifier NCT01491763).
Methods
Patients aged 18 to 55 years with de novo Ph+ ALL were treated with imatinib concurrently with standard‐dose induction and consolidation therapy followed by allogeneic hematopoietic stem cell transplantation (allo‐HSCT) when possible. In patients with first disease recurrence, the authors analyzed the type of recurrence, timing, location, presence of kinase domain mutations, type of treatment, and outcomes.
Results
Of the 125 patients, 28 patients (22%) developed disease recurrence before (4 patients) or after (24 patients) HSCT, with the recurrences being molecular in 11 patients (39%) and overt in 17 patients (61%). T315I was the most common mutation noted at the time of disease recurrence. Change in TKI was the most frequent treatment for patients with molecular disease recurrence whereas rescue chemotherapy and TKI change followed by second allo‐HSCT when possible were performed for the most part in patients with overt disease recurrence. A total of 20 patients (71%) achieved response. The median disease‐free survival (DFS) and overall survival (OS) were 8.5 months and 15.3 months, respectively. A trend for better DFS and OS was observed in patients with molecular recurrence compared with those with overt recurrence (median of 16.9 months vs 6.3 months P = .05 and 28.7 months vs 11.5 months P = .05 for DFS and OS, respectively).
Conclusions
Disease recurrence was frequent in young and older adults with Ph+ ALL who were treated with imatinib and chemotherapy with HSCT. Although the majority of patients responded to rescue therapy, their outcomes were poor, especially with regard to overt disease recurrence.
Outcomes after first disease recurrence in adults with Philadelphia chromosome–positive acute lymphoblastic leukemia are poor. Patients with overt disease recurrence appear to have a worse prognosis compared with those with molecular recurrence.
Summary
The prognosis of t(1;19)(q23;p13)/transcription factor 3‐pre‐B‐cell leukaemia homeobox 1 (TCF3‐PBX1) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with ...measurable residual disease (MRD)‐oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric‐inspired trials. The patients with TCF3‐PBX1 showed similar MRD clearance and did not have different survival compared with other B‐cell precursor ALL patients. However, patients with TCF3‐PBX1 had a significantly higher cumulative incidence of relapse, especially among patients aged ≥35 years carrying additional cytogenetic alterations. These patients might benefit from additional/intensified therapy (e.g. immunotherapy in first complete remission with or without subsequent haematopoietic stem cell transplantation).
Objectives
High‐dose total body irradiation (TBI) is considered a cornerstone of myeloablative conditioning for allogeneic stem cell transplantation (allo‐SCT). We retrospectively compared the main ...outcomes of an HLA matched or 1‐allele mismatched related or unrelated allo‐SCT in adult patients affected by acute leukemia (AL) or myelodysplastic syndromes (MDS).
Methods
Fifty‐nine patients received cyclophosphamide (Cy)‐TBI (13.5 Gy) and graft‐versus‐host disease (GVHD) prophylaxis with a calcineurin‐inhibitor plus methrotrexate (CyTBI group) and 28 patients received fludarabine‐TBI (8.8–13.5 Gy) and GVHD prophylaxis with PTCy and tacrolimus (FluTBI‐PTCy group).
Results
Median follow‐up for survivors was 82 and 22 months. The 12‐month probability of overall survival and progression‐free survival were similar (p = .18, p = .7). The incidence of Grades 2–4 and 3–4 acute GVHD, and the incidence of moderate‐to‐severe chronic GVHD were higher in the CyTBI group (p = .02, p < .01and p = .03). Nonrelapse mortality (NRM) at 12 months posttransplant was higher in the CyTBI group (p = 0.05), while the incidence of relapse was similar in both groups (p = 0.7). The number of GVHD‐free and relapse‐free patients without systemic immunosuppression (GRFS) at 1‐year posttransplant was higher in the FluTBI‐PTCy group (p = 0.01).
Conclusions
The study confirms the safety and efficacy of a novel FluTBI‐PTCy platform with reduced incidence of severe acute and chronic GVHD, and early improvement of NRM.
Post‐transplant lymphoproliferative disorder (PTLD) is an infrequent complication of allogeneic stem cell transplant (allo‐SCT).
Aims
To estimate the frequency and management of PTLD in Spain and to ...identify prognostic factors influencing outcomes.
Methods
Multicenter, retrospective analysis of allo‐SCT performed in 14 transplant units over a 15‐year period.
Results
102 PTLD were diagnosed among 12 641 allo‐SCT, leading to an estimated frequency of 0.8%. PTLD was diagnosed at a median of 106 days after SCT. Eighty‐seven cases (85%) were diagnosed between 2007 and 2013. At diagnosis, 22% and 17% of the patients had gastrointestinal tract and CNS involvement. Eighty‐seven (85%) received rituximab treatment, alone or in combination with immunosuppression reduction, with an ORR of 50.6%. With a median follow‐up for survivors of 58 months, the 2‐year overall survival (OS) was 33% and the PTLD‐related mortality 45%. Age ≥ 40 years, malignant underlying disease, non‐response to rituximab, and severe thrombocytopenia or lymphocytopenia at PTLD diagnosis were associated with worse overall survival.
Conclusions
Only a small proportion of allografted patients were diagnosed a PTLD. Its clinical course was highly aggressive, and prognosis poor, especially in those failing rituximab. The prognostic impact found of the platelet, and lymphocyte count at diagnosis requires further confirmation.
Objective and Methods
Severe postengraftment thrombocytopenia is a common complication after allogeneic stem cell transplantation (alloSCT). A few studies have suggested that the use of ...thrombopoietin agonists (TPOa) may be useful in this setting. Our retrospective study is the largest series published to date; we retrospectively evaluated TPOa efficacy and safety in 20 adult alloSCT recipients who received TPOa as a compassionate use for clinically relevant thrombocytopenia.
Results
Twelve of 20 patients (60%) responded, with a 180‐day cumulative incidence of successful platelet recovery to ≥30 and ≥50 × 109/L of 57% (95% CI: 44%‐71%) and 32% (95% CI: 18%‐46%), respectively, which were reached at a median of 28 and 34 days from the start of therapy. Fifty percent of the responders were able to discontinue the TPOa without recurrence of severe thrombocytopenia and its associated hemorrhagic complications. No serious adverse events were reported. Possible variables associated with higher response to TPOa were as follows: age < 40 years, presence of megakaryocytes in the bone marrow aspirate, and/or prior response to other hematopoietic growth factors.
Conclusion
This study adds further enthusiasm for continued research on the use of these agents for the treatment of persistent thrombocytopenia in alloSCT recipients.
Introduction
Increased levels of Wilms’ tumor (WT1) mRNA have been used to establish risk categories in patients with acute myeloid leukemia (AML). Raised values of WT1 have been associated with ...progression in myelodysplastic syndrome (MDS).
Methods
We retrospectively analyzed the available bone marrow (BM) samples from 115 patients with myeloid neoplasms obtained before and during treatment with 5‐azacytidine. A threshold of 100 copies in BM was used to define risk groups: group 1: patients with WT1 levels always below < 100 copies; group 2: cases with initial WT1 levels greater than 100 copies but with a conversion to sustained levels below 100; and group 3: cases with follow‐up WT1 levels greater than 100.
Results
Twenty patients were included in group 1, 17 in group 2, and 78 in group 3. Survival analysis showed statistically significant differences in terms of OS between groups (p: 0.016). Patients in group 2 showed the best 5‐year overall survival (OS). In multivariate analysis, only the cytogenetic risk category and receiving an allogeneic hematopoietic stem cell transplantation (HCT) independently predicted the survival.
Conclusions
Further studies are needed to assess whether BM WT1 levels could be useful to predict the survival of patients with myeloid neoplasms treated with 5‐azacytidine.
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