Annals of Hematology最新文献

Patient-reported outcomes (PROs) are crucial endpoints in multiple myeloma (MM) randomized controlled trials (RCTs), yet there is significant variability in their methodology and reporting. Our study aimed to (a) identify the most commonly pre-specified PRO domains in MM RCTs and those most responsive to modern therapies, and (b) examine the association between PROs and progression-free survival (PFS)/overall survival (OS). We performed a systematic review of MM RCTs that used EORTC QLQ-C30 and published between 01/2014-06/2023. The association between PFS/OS and PRO was explored using Fisher's exact test or Pearson's Chi-squared test. Thirty-five RCTs were identified, with PROs as secondary or exploratory endpoints in all studies. About one-third of RCTs (n=11, 31.4%) pre-specified at least one EORTC QLQ-C30 domain, with the most common domains being Global health status/Quality of life (GHS/QoL) (n = 10, 90.9%), Physical Functioning (n = 6, 54.5%), Fatigue (n = 6, 54.5%), and Pain (n = 6, 54.5%). A statistically significant and/or clinically meaningful difference in at least one EORTC QLQ-C30 domain between arms was seen in 23/35 trials (65.7%), with the most common domains showing improvement being GHS/QoL (12/23 trials), Pain (11/23 trials), Fatigue (9/23 trials), and Physical Functioning (9/23 trials). PRO was noted to be concordant with PFS in 19/33 (57.6%) trials (p = 0.398), and with OS in 22/31 (71%) trials (p = 0.018). Our study identified key PRO domains that can be potentially used as primary endpoint in MM RCTs. Additionally, significant association between PROs and OS highlight the importance of integrating PROs to better capture treatment efficacy.

Chediak-Higashi syndrome (CHS) is a life-threatening autosomal recessive immunodeficiency disease presenting with recurrent infections, hypopigmentation, progressive neurodegeneration, and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated stage. Two-thirds of patients experience a fatal accelerated phase. CHS is caused by lysosomal transport regulator (LYST) gene mutations. We report the case of CHS, who was born with pale skin and silver hair. Bone marrow aspirate revealed large inclusions in granulocytes, monocytes, and lymphocytes. Genetic analysis revealed a new nonsense mutation in the LYST gene: c.8186G > A (W2729Ter). The child presented with fever, hepatosplenomegaly, and lymphadenectasis. Laboratory tests showed pancytopenia, hypofibrinogenemia, and high serum ferritin, indicating an accelerated phase of CHS. She underwent allogeneic hematopoietic stem cell transplantation (HCST) combined with umbilical cord blood transplantation (UCBT) after HLH-related chemotherapy. The patient has been alive for nine months without recurrence. We have identified a novel nonsense mutation in the LYST gene that correlates with a severe phenotype, and HSCT combined with UCBT is an effective treatment.

Bone marrow reactive T-cell infiltrates have been frequently observed in patients affected by follicular lymphoma after rituximab treatment. In some studies, bone-marrow T-cell expansion has been associated with an effective anti-tumor response and favorable prognosis. In this manuscript, we report on a particularly brisk CD4⁺ T-cell reaction occurring after rituximab treatment for follicular lymphoma and involving the peripheral blood in addition to the bone marrow. Peripheral blood T-cell reaction was mainly composed of effector-memory CD4⁺ T cells and may reflect the expansion of an effective anti-tumor immunity.

Pure red cell aplasia is a rare condition that may be congenital or associated with an underlying disease.Immunosuppressants are a commonly employed therapeutic option for the treatment of pure red cell aplasia;however, they are associated with considerable adverse effects, including nephrotoxicity. This case report describesa 74-year-old patient with pure red cell aplasia who developed long-term kidney injury following cyclosporinetherapy. Renal anemia is a common complication after chronic kidney injury and contributes to the poor outcome ofanemia treatment. Following a series of medication adjustments, the final treatment with roxarestat combined withsirolimus proved effective in delaying the impairment of this patient's kidney function, with the hemoglobin levelremaining above 100 g/L throughout. This case report demonstrates the efficacy of roxarestat in conjunction with animmunosuppressive agent in the treatment of pure red cell aplasia combined with kidney injury, with a dual effect ofalleviating the anemia and reducing serum creatinine levels.

Elotuzumab-based regimens are sometimes selected for multiple myeloma treatment after daratumumab-based regimens. However, there has been insufficient discussion on the efficacy of elotuzumab after daratumumab. We used Kansai Myeloma Forum registration data in a multicenter retrospective evaluation of the efficacy of elotuzumab after daratumumab. Overall survival (OS) rate and time to next treatment (TTNT) were significantly worse in the cohort given elotuzumab after daratumumab (Dara cohort, n = 47) than in the cohort with no history of daratumumab administration before elotuzumab (No-Dara cohort, n = 80, OS: P = 0.03; TTNT: P = 0.02; best response: P < 0.01). In the Dara cohort, OS and TTNT rates were worse with sequential elotuzumab use after daratumumab than with non-sequential (OS: P = 0.02; TTNT: P = 0.03). In patients given elotuzumab < 180 days after daratumumab, OS (P = 0.08) and best response (P = 0.21) tended to be worse, and TTNT was significantly worse (P = 0.01), than in those given elotuzumab after ≥ 180 days. These findings were confirmed by subgroup analyses and multivariate analyses. Monoclonal-antibody-free treatment might be preferable after daratumumab-based regimens. If possible, elotuzumab-based regimens should be considered only ≥ 180 days after daratumumab use.

Lymphoma and plasma cell disorders are the most common indications for autologous hematopoietic stem cell (HSC) transplantation. We conducted a prospective multicenter study with the aim of testing the feasibility of plerixafor (PLX) in combination with R-DHAP and G-CSF in 37 patients with relapsed refractory diffuse large B-cell lymphoma (R/R DLBCL) in order to collect a large number of HSC with a goal of transplantation. After R-DHAP, daily monitoring of peripheral blood CD34 + cells by flow cytometry was performed starting on day + 13. If, on day + 14, peripheral blood CD34 + cells were > 20 × 10e6/L apheresis was started, if they were < 20 × 10e6/L and WBC > 4.0 × 10e9/L, PLX was administered. Results: The median CD34 + cell count collected was 10.5 × 10e6/kg (range 0-51). 81% of patients achieved the minimum CD34 + target cell count of 6 × 10e6/kg. 66% of patients required only one apheresis to achieve collection goals. The rate of engraftment was 10 days for neutrophils > 0.5 × 10e9/L and 13 days for platelets > 20 × 10e9/L. In conclusion, the addition of PLX to salvage therapy in patients with R/R DLBCL is effective and may be routinely used in the future to increase the number of CD34 + cells collected and minimize the risk of poor mobilization.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a crucial treatment option for children with M2 subtype acute myeloid leukemia (AML). Human herpesvirus 6 (HHV-6) encephalitis following transplantation is a rare postoperative complication, with a poor prognosis and a high fatality rate in allo-HSCT recipients. In this report, a juvenile patient with AMLwas successfully treated after developing visual impairment as a result of HHV-6B encephalitis during allo-HSCT therapy. HHV-6 encephalitis-associated visual impairment after transplantation is rare, and clinical diagnosis and treatment are challenging, requiring more attention in the future.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm (MPN characterized by reciprocal translocation in the ABL1 and BCR region of chromosomes 9 and 22 respectively. Progression to the blast phase in chronic myeloid leukemia results in a poorer prognosis. It can be of either myeloid, lymphoid or a mixed lineage. Progression to the promyelocytic blast phase is very rare, and there are no evidence-based guidelines for its management. Thrombosis in CML is not well defined. Thrombosis can be seen in patients with acute promyelocytic leukemia (APL) with venous thrombosis (VTE) being more common than arterial thrombosis. Ischemic stroke as the presenting feature of blast phase progression in CML is extremely rare. We report a case of CML who presented to us with acute ischemic stroke and subsequently was diagnosed as CML transformed to the promyelocytic blast phase. She was successfully treated with dasatinib along with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO).