A combination of three post-transplant drugs, cyclophosphamide (PTCy), a calcineurin inhibitor, and mycophenolate mofetil, has long been used for prophylaxis of graft-versus-host-disease (GVHD) after ...HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT). Recently, this combination has been used following HLA-matched allo-HCT as well, but the optimal combination of drugs for GVHD prophylaxis in an HLA-matched setting remains unclear. This prospective phase II study evaluated the safety and efficacy of PTCy plus tacrolimus (TAC) for GVHD prophylaxis after allo-HCT from HLA-matched related donors (MRD) or HLA-matched unrelated donors (MUD). The cumulative incidences of grades II–IV and III–IV acute GVHD at 100 days post-transplantation were 18% and 5.9%, respectively, in the MRD group, and 18% and 9.1%, respectively, in the MUD group. The cumulative incidences of moderate to severe chronic GVHD at 1 year were 12% and 9.1% in the MRD and MUD groups, respectively. The 1-year overall survival rates in the MRD and MUD groups were 88% and 64%, respectively, and the 1-year GVHD-free, relapse free survival rates were 59% and 50%, respectively. These results suggest that GVHD prophylaxis with a less intensive double drug combination (PT/Cy and TAC) might be feasible after HLA-matched allo-HCT.
Clinical Trial Notation
This trial was a prospective single-center trial registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification number: UMIN000023890) and the Japan Registry of Clinical Trials (jRCTs051180143).
High-dose cytarabine (HD-AraC) or anthracycline-containing chemotherapies are used as post-remission therapy for acute myeloid leukemia (AML) patients. However, it remains unclear which regimen would ...be better as post-remission therapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thus, we compared the incidence of cardiac events and event-free survival (EFS) after allo-HSCT at two Japanese hospitals between HD-AraC and anthracycline-containing post-remission therapy to clarify the safety of post-remission therapy. Of a total of 132 patients, 68 received HD-AraC (HD-AraC group) and 64 received anthracycline-containing chemotherapy (ANT group). HD-AraC was preferentially selected for core-binding factor AML patients (
p
= 0.008). The median cumulative anthracycline dose was 115.2 mg/m
2
in the HD-AraC group and 318.7 mg/m
2
in the ANT group (
p
< 0.0001). Cardiac events were observed in 18 (13.6%) patients during the follow-up period. The 3-year cumulative incidence of cardiac events was 9.1% in the HD-AraC group and 11.0% in the ANT group (
p
= 0.70). EFS at 3 years after allo-HSCT was 40.9% in the HD-AraC group and 39.6% in the ANT group (
p
= 0.51). In conclusion, incidence of cardiac events did not differ significantly between post-remission therapy regimens in AML patients who underwent allo-HSCT.
Hyperviscosity syndrome (HVS) is a complication of monoclonal plasma cell tumors. The frequency of HVS depends on the type of monoclonal protein. Immunoglobulin M (IgM) is more closely associated ...with HVS than IgG, and among IgG subclass monoclonal proteins, IgG3 is most frequently associated with HVS. We herein report a 44-year-old woman with multiple myeloma (MM), HVS, and cryoglobulinemia. Her monoclonal protein and cryoglobulin were IgG1-lambda (λ). She developed HVS at a lower monoclonal protein level because of the properties of the IgG1-derived monoclonal protein and cryoglobulin. Our case highlights the fact that identifying the IgG subclass is useful in predicting the risk of complicating HVS.
Bone marrow necrosis (BMN) is a rare but important complication of hematological malignancies. We report the case of a 52-year-old male patient with a recurrence of acute lymphoblastic leukemia (ALL) ...accompanied by BMN. After re-induction therapy, bone marrow aspiration (BMA) and biopsy from the iliac bone showed necrotic cells and eosinophilic debris, respectively. Magnetic resonance imaging (MRI) showed heterogeneous signals in the bilateral iliac bone, possibly reflecting various stages of BMN. BMA from the sternum eventually revealed the recurrence of ALL after a few weeks. Comprehensive assessments, including MRI and repeated bone marrow tests, are required when evaluating the underlying hematological malignancies of patients with BMN.
The optimal dose of posttransplant cyclophosphamide (PTCy) for use in patients undergoing HLA-haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (PTCy-haplo) has ...not been sufficiently examined. This study evaluates the safety and efficacy of HLA-haploidentical hematopoietic cell transplantation with a reduced dose of PTCy for patients with a poor prognosis or those with refractory hematological malignancies. We conducted a prospective clinical study of PTCy-haplo with peripheral blood stem cells (PBSCs) using a modified PTCy dosage regimen consisting of 50 mg/kg on day 3 posttransplantation and a reduced dose of 25 mg/kg on day 4. The cumulative incidences of grades II to III and IV acute graft-versus-host disease (GVHD) at day 100 posttransplantation were 30% and 0%, respectively. The cumulative incidence of moderate-to-severe chronic GVHD after transplantation was 7.0%. The cumulative incidence of nonrelapse mortality at 1 year posttransplantation was 6.1%. Overall survival (OS) at 1 year was 66%. In addition, the restricted cubic-spline Cox regression analysis showed nonlinear relationship between the number of infused CD34+ cells and CD3+ cells, and OS. A graft composition of >4.54 × 106/kg CD34+ cells and >1.85 × 108/kg but ≤3.70 × 108/kg CD3+ cells was significantly associated with better survival, irrespective of the disease status (hazard ratio, 0.13; 95% confidence interval, 0.04–0.41; P < 0.001). These results suggest that PTCy-haplo with PBSCs using a de-escalated dose of 50 mg/kg on day 3 and 25 mg/kg on day 4 posttransplantation is a feasible option.
Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous reports suggest that TA-TMA is caused ...by complement activation by complement-related genetic variants; however, this needs to be verified, especially in adults. Here, we performed a nested case-control study of allo-HSCT-treated adults at a single center. Fifteen TA-TMA patients and 15 non-TA-TMA patients, matched according to the propensity score, were enrolled. Based on a previous report showing an association between complement-related genes and development of TA-TMA, we first sequenced these 17 genes. Both cohorts harbored several genetic variants with rare allele frequencies; however, there was no difference in the percentage of patients in the TA-TMA and non-TA-TMA groups with the rare variants, or in the average number of rare variants per patient. Second, we measured plasma concentrations of complement proteins. Notably, levels of Ba protein on Day 7 following allo-HSCT were abnormally and significantly higher in TA-TMA than in non-TA-TMA cases, suggesting that complement activation
the alternative pathway contributes to TA-TMA. All other parameters, including soluble C5b-9, on Day 7 were similar between the groups. The levels of C3, C4, CH50, and complement factors H and I in the TA-TMA group after Day 28 were significantly lower than those in the non-TA-TMA group. Complement-related genetic variants did not predict TA-TMA development. By contrast, abnormally high levels of Ba on Day 7 did predict development of TA-TMA and non-relapse mortality. Thus, Ba levels on Day 7 after allo-HSCT are a sensitive and prognostic biomarker of TA-TMA.
Extended use of oseltamivir in an immunocompromised host could reportedly induce neuraminidase gene mutation possibly leading to oseltamivir-resistant influenza A/H3N2 virus. To our knowledge, no ...report is available on the clinical course of a severely immunocompromised patient with a dual E119D/R292K neuraminidase mutated-influenza A/H3N2 during the administration of peramivir. In a highly immunocompromised host, clinicians should take care when peramivir is used for extended periods to treat influenza virus A/H3N2 infection as this could potentially leading to a dual E119D/R292K substitution in neuraminidase protein. Baloxavir marboxil may be one of the agents that can be used to treat this type of mutated influenza virus infection.
Quality of life of patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) temporally deteriorates and recovers over several years. We retrospectively evaluate the impact of ...chronic graft-versus-host disease (GVHD) and glucocorticoid on physical recovery. We included 162 patients who underwent their first allogeneic HSCT between October 2010 and December 2015 in a single hospital. All patients are planned to undergo physical function tests before and 1, 3, 12 months after allogeneic HSCT. Scores of knee extension strength and distance covered in the 6-min walk test (6MWT) recovered at the 12-month assessment. Both chronic GVHD and high dose glucocorticoid were associated with delayed recovery of body mass index (BMI), hand grip strength, knee extension strength, and duration of standing on one foot. Lung GVHD and high dose glucocorticoid had negative impact on the distance covered in the 6MWT. A multivariate analysis revealed that chronic GVHD and glucocorticoid was an independent risk factor for decreased BMI and delayed recovery of muscle strength, respectively. Our results suggest that high-risk patients who have chronic GVHD or who receive glucocorticoid therapy may require reduced dose of glucocorticoid and long-term physical support to recover physical function after transplantation.
Reinduction therapy with L-asparaginase was initiated, but bone marrow examination again demonstrated recurrent T-ALL. ...he received salvage therapy with nelarabine (1500 mg/m2) on days 1 and 3. ...CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest. CLINICAL TRIAL REGISTRATION The authors have confirmed clinical trial registration is not needed for this submission.
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