Background
Recombinant human granulocyte–colony‐stimulating factor (G‐CSF) is used to mobilize hematopoietic stem cells for both autologous and allogeneic hematopoietic stem cell transplantation. The ...recombinant products clinically available are lenograstim and filgrastim, which differ from a biologic point of view as well as from their economical impact. In this regard, some studies have shown different in vitro activities although clinical studies comparing both drugs in the allogeneic transplant setting are scanty.
Study Design and Methods
In the current study we compare the efficacy of lenograstim and filgrastim in terms of number of circulating CD34+ cells/μL during the fifth day of G‐CSF administration, the number of days of apheresis required to obtain the target cell dose, the median of CD34+ cells collected on the first day of apheresis, or the median number of total CD34+ cells collected at the end of the procedure, in a series of 146 healthy donors undergoing hematopoietic stem cell mobilization for allogeneic transplantation.
Results
We observed that, using a comparable dose for the two products, no significant differences were observed between the two groups.
Conclusion
In conclusion, the current retrospective study shows that lenograstim and filgrastim are similar in terms of efficacy for the mobilization of hematopoietic stem cells in healthy donors.
Severe infections and their attributable mortality are major complications in recipients of allogeneic hematopoietic stem cell transplantation (alloSCT). We herein report 236 adult patients who ...received haploSCT with PTCy. The median follow-up for survivors was 37 months. The overall incidence of bloodstream infections by gram-positive and gram-negative bacteria at 37 months was 51% and 46%, respectively. The incidence of cytomegalovirus infection was 69%, while Epstein Barr virus infections occurred in 10% of patients and hemorrhagic cystitis in 35% of cases. Invasive fungal infections occurred in 11% at 17 months. The 3-year incidence of infection-related mortality was 19%. The median interval from transplant to IRM was 3 months (range 1-30), 53% of IRM occurred >100 days post-haploSCT. Risk factors for IRM included age >50 years, lymphoid malignancy, and developing grade III-IV acute GvHD. Bacterial infections were the most common causes of IRM (51%), mainly due to gram-negative bacilli BSI. In conclusion, severe infections are the most common causes of NRM after haploSCT with PTCy, with a reemergence of gram-negative bacilli as the most lethal pathogens. More studies focusing on the severe infections after haploSCT with PTCy and differences with other types of alloSCT in adults are clearly warranted.
Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined.
This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective ...observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020.
We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p = 0.011; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p < 0.0001); ECOG 3-4 (OR, 2.56, 95% CI 1.4-4.7, p = 0.003); neutropenia (< 0.5 × 10
/L) (OR 2.8, 95% CI 1.3-6.1, p = 0.01); and a C-reactive protein (CRP) > 20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P = 0.1).
In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19.
Background. The benefit of the combination of serum galactomannan (GM) assay and polymerase chain reaction (PCR)–based detection of serum Aspergillus DNA for the early diagnosis and therapy of ...invasive aspergillosis (IA) in high-risk hematological patients remains unclear. Methods. We performed an open-label, controlled, parallel-group randomized trial in 13 Spanish centers. Adult patients with acute myeloid leukemia and myelodysplastic syndrome on induction therapy or allogeneic hematopoietic stem cell transplant recipients were randomized (1:1 ratio) to 1 of 2 arms: "GM-PCR group" (the results of serial serum GM and PCR assays were provided to treating physicians) and "GM group" (only the results of serum GM were informed). Positivity in either assay prompted thoracic computed tomography scan and initiation of antifungal therapy. No antimold prophylaxis was permitted. Results. Overall, 219 patients underwent randomization (105 in the GM-PCR group and 114 in the GM group). The cumulative incidence of "proven" or "probable" IA (primary study outcome) was lower in the GM-PCR group (4.2% vs 13.1%; odds ratio, 0.29 95% confidence interval, .09–.91). The median interval from the start of monitoring to the diagnosis of IA was lower in the GM-PCR group (13 vs 20 days; P = .022), as well as the use of empirical antifungal therapy (16.7% vs 29.0%; P = .038). Patients in the GM-PCR group had higher proven or probable IA–free survival (P = .027). Conclusions. A combined monitoring strategy based on serum GM and Aspergillus DNA was associated with an earlier diagnosis and a lower incidence of IA in high-risk hematological patients.
Continuation of empirical antimicrobial therapy (EAT) for febrile neutropenia in patients with haematological malignancies until neutrophil recovery could prolong the therapy unnecessarily. We aimed ...to establish whether EAT discontinuation driven by a clinical approach regardless of neutrophil recovery would optimise the duration of therapy.
We did an investigator-driven, superiority, open-label, randomised, controlled phase 4 clinical trial in six academic hospitals in Spain. Eligible patients were adults with haematological malignancies or haemopoietic stem-cell transplantation recipients, with high-risk febrile neutropenia without aetiological diagnosis. An independent, computer-generated randomisation sequence was used to randomly enrol patients (1:1) to the experimental or control group. Investigators were masked to assignment only before randomisation. EAT based on an antipseudomonal β-lactam drug as monotherapy (ceftazidime or cefepime, meropenem or imipenem, or piperacillin-tazobactam) or as combination therapy (with an aminoglycoside, fluoroquinolone, or glycopeptide) was started according to local protocols and following international guidelines and recommendations. For the experimental group, EAT was withdrawn after 72 h or more of apyrexia plus clinical recovery; for the control group, treatment was withdrawn when the neutrophil count was also 0·5 × 10
cells per L or higher. The primary efficacy endpoint was the number of EAT-free days. Primary analyses were done in the intention-to-treat population. Efficacy and safety analyses were done in the intention-to-treat population and the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT01581333.
Between April 10, 2012, and May 31, 2016, 157 episodes among 709 patients assessed for eligibility were included in analyses. 78 patients were randomly assigned to the experimental group and 79 to the control group. The mean number of EAT-free days was significantly higher in the experimental group than in the control group (16·1 SD 6·3 vs 13·6 7·2, absolute difference -2·4 95% CI -4·6 to -0·3; p=0·026). 636 adverse events were reported (341 in the experimental group vs 295 in the control group; p=0·057) and most (580 91%; 323 in the experimental group vs 257 in the control group) were considered mild or moderate (grade 1-2). The most common adverse events in the experimental versus the control group were mucositis (28 36% of 78 patients vs 20 25% of 79 patients), diarrhoea (23 29% of 78 vs 24 30% of 79), and nausea and vomiting (20 26% of 78 vs 22 28% of 79). 56 severe adverse events were reported, 18 in the experimental group and 38 in the control group. One patient died in the experimental group (from hepatic veno-occlusive disease after an allogeneic haemopoietic stem-cell transplantation) and three died in the control group (one from multiorgan failure, one from invasive pulmonary aspergillosis, and one from a post-chemotherapy intestinal perforation).
In high-risk patients with haematological malignancies and febrile neutropenia, EAT can be discontinued after 72 h of apyrexia and clinical recovery irrespective of their neutrophil count. This clinical approach reduces unnecessary exposure to antimicrobials and it is safe.
Instituto de Salud Carlos III, Spanish Ministry of Economy (PI11/02674).
Transformation of follicular lymphoma into an aggressive lymphoma (tFL) worsens the prognosis and the standard treatment is not completely defined. Allogeneic hematopoietic stem cell transplantation ...(alloSCT) could be a potentially curative option for these patients, but it has not been widely explored.
We designed a retrospective multicenter study to analyze the efficacy and toxicity of alloSCT in tFL patients and potential prognostic factors of survival.
A total of 43 patients diagnosed with tFL who underwent alloSCT in 14 Spanish centers between January 2000 and January 2019 were included. Median age was 44 (31-67) years. After a median follow-up of 58 months, estimated 5-year overall survival (OS) and progression-free survival (PFS) were both 35%. Estimated 100-day and 1-year non-relapse mortality (NRM) were 20% and 34%, respectively. The type of conditioning regimen (3-year OS of 52% vs. 20%, respectively, for reduced-intensity vs. myeloablative conditioning) and development of chronic graft versus host disease (cGVHD) (3-year OS of 75% vs. 40%) were the only factors significantly associated with OS. The only variable with an independent association with OS was cGVHD (HR, 3.4; 95% CI, 1.2-9.6).
Our results indicate that alloSCT continues to be a potentially curative option for patients with tFL.
Background. Isolated case reports have shown that recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who develop toxoplasmosis may have circulating Toxoplasma gondii DNA in ...peripheral blood before the onset of clinical symptoms. Methods. We prospectively studied 106 T. gondii—seropositive adult recipients of HSCTs for the incidence of reactivation of toxoplasmosis in the first 6 months after transplantation. Toxoplasmosis infection (TI) was defined by a positive result of polymerase chain reaction (PCR) of peripheral blood specimens, whereas toxoplasmosis disease (TD) was defined as an invasive infection. Results. The incidence of TI was 16% (95% confidence interval CI, 8%–21%), whereas the incidence of TD was 6% (95% CI, 1%–10%). In the 16 patients with TI, the incidence of disease was 38%, whereas it was 0% in patients without TI (P < .0001). In most patients, the onset of TD or treatment for TI was preceded by an increase in the parasite load in peripheral blood samples, as determined by quantitative PCR. Conclusions. Toxoplasmosis occurs more commonly after HSCT than has previously been suggested, and routine PCR testing of peripheral blood specimens may be an appropriate tool for guiding preemptive therapy in patients at very high risk of developing invasive disease.
The use of checkpoint blockade therapy (CBT) has shown impressive results for the treatment of relapsed/refractory Hodgkin lymphoma (cHL). The impact of CBT depends on the reversal of an exhausted ...T-cell immune phenotype and a consequential increase in the immunological, anti-tumor effect derived from a patient's adaptive immunity. As most patients with classical Hodgkin lymphoma will relapse during or after this treatment, clinicians often provide consolidation with allogeneic hematopoietic cell transplantation (alloHCT) in fit patients. However, the mechanisms responsible for CBT efficacy can also be those that increase the risk of immunological complications after alloHCT.
We carried out in-depth research on the current medical literature to report and discuss the mechanism of action of CBT within a cHL setting; clinical results of CBT in cHL setting pre-alloHCT and post-alloHCT; interactions between CBT and alloHCT; and further clinical considerations.
Checkpoint blockade therapy is an effective strategy for relapsed/refractory cHL. Its use is associated with higher immunological toxicities when administered before or after alloHCT. Whenever alloHCT is planned, clinicians should follow international recommendations such as using post-transplant cyclophosphamide GVHD prophylaxis.
PDF
