A clinical study of allogeneic hematopoietic stem cell transplantation in 23 patients with early T-cell precursor acute lymphoblastic leukemia / 中华血液学杂志

Objective: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk T lymphoblastic leukemia subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we explore the efficacy and outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ETP-ALL. Methods: The clinical data of 23 patients with ETP-ALL receiving allo-HSCT from 2010 to 2018 were retrospectively analyzed. Patients with ETP-ALL were diagnosed based on the characteristic immunophenotypes. Second-generation sequencing was done in all patients. As to the donors, 12 patients had haploidentical donors (Haplo-HSCT) , 7 HLA-matched sibling donors (Sib-HSCT) and 4 HLA-matched unrelated donors (URD-HSCT) . Before transplantation, 19 patients achieved complete remission (CR) and 4 patients without. Results: The main clinical features of ETP-ALL included high white blood cell counts in 5 patients, splenomegaly in 14, lymphadenopathy in 19, and thymus masses in 5. According to cytogenetic and molecular characteristics, 11 patients had gene mutations related to myeloid tumors, and 7 with high risk Karyotype. After first induction regimen, 14/23 patients achieved CR. 5 patients reached CR after more than 2 cycles of chemotherapy, while another 4 patients did not reach CR. After allo-HSCT, 22 patients were successfully implanted. The median time of granulocyte and platelet reconstitution was +12 and +19 days. One patient died of transplant-related infection at +14 days. The estimated 18-month overall survival (OS) and relapse-free survival (RFS) rates were (55.0±14.4) % and (48.1±14.7) % respectively. Transplant-related mortality was 4.3%. The median OS in patients achieving CR before transplantation was 20 months, however, that in patients without CR was only 13 months. OS and RFS between haplo-HSCT and sib-HSCT were comparable (P=0.460 and 0.420 respectively) . Conclusions: Allo-HSCT is an effective therapy in some patients with ETP-ALL. Salvage HSCT cannot overcome the poor outcome. Haplo-HSCT and sib-HSCT in ETP-ALL patients have the similar clinical outcome.

CYP2C19 genetic polymorphism and monitoring voriconazole plasma concentrations in the treatment and prevention of invasive fungal disease for hematological patients / 中华血液学杂志

Objective: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). Methods: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (Ctrough) was detected by ultra performance liquid chromatography tandem mass spectrometry. Results: Based on the genotype analysis, 65 subjects were identified as extensive metabolizers' group (30 cases) and poor metabolizers' group (35 cases). The Ctrough of the 65 patients were detected for 169 times totally, and there was a significant difference of Ctrough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of Ctrough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ2=11.689, P=0.020). Conclusion: Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their Ctrough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.

Clinical characteristics of healthcare-associated infection in initially treated patients with multiple myeloma during the induction period / 中国感染控制杂志

Objective To explore the infection status and clinical characteristics of healthcare-associated infection (HAD in patients initially diagnosed with multiple myeloma(MM) during the induction period.Methods Clinical data of 116 patients diagnosed with MM and initially treated with PAD(bortezomib + adriamycin + dexamethasone)or PDD(bortezomib + liposome doxorubicin + dexamethasone) regimen in a hospital were collected,infection rates and clinical characteristics of patients during the induction therapy period were analyzed statistically.Results Among 116 patients,69 received PAD regimen,and 47 received PDD regimen,infection rates in two groups were 79.7％ and 89.4％ respectively;73 patients received subcutaneous injection of bortezomib,43 received intravenous injection of bortezomib,infection rates in subcutaneous injection group and intravenous injection group were 78.1％ and 93.0％ respectively,difference was statistically significant between two groups(P＜0.05).During the induction period,HAI rate was 83.6％ (n =97),81 patients developed infection during the first course,infection status of 3 patients were not clear due to therapy outside the hospital,the actual infection rate was 71.7 ％ (81/113);infection rate during the second course was 56.6 ％ (64/113);a total of 98 patients completed three therapy courses,infection rate was 43.9％ (43/98);66 patients completed four therapy courses,infection rate was 28.8％ (19/66).With the increase of the therapy course,infection rate showed a downward trend.Infection sites from high to low were respiratory system,skin and mucosa,oral and gastrointestinal system,bloodstream,and urinary tract.Difference in constitute of clinical diagnosis between patients receiving and without receiving prophylactic antifungal agents during chemotherapy period was not statistically significant (P =0.063).Conclusion Infection rate is very high during induction period,the main infection site is respiratory system,clinicians and patients need to pay more attention to the prevention and treatment of respiratory system infection.

Efficacy and safety study of subcutaneous injection of bortezomib in the treatment of de novo patients with multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy and safety of subcutaneous injection of bortezomib in the treatment of de novo multiple myeloma (MM) patients.</p><p><b>METHODS</b>A total of 36 MM patients treated with bortezomib, adriamycin and dexamethasone (PAD) from January 2012 to April 2013 were analyzed. Among them, 18 received improved PAD (improved PAD group) with the subcutaneous injection of bortezomib, another 18 received conventional PAD (PAD group). The efficacy and safety of two groups were analyzed.</p><p><b>RESULTS</b>Except 4 cases can not be assessed, 32 patients were evaluated. Of 32 cases, 19(59.4%) achieved complete remission (CR) or very good partial remission (VGPR) after induction therapy, which were 61.1% and 57.1% for PAD group and improved PAD group, respectively (P=1.000). No significant difference between the time to achieve maximum effectiveness in two groups was detected. In the PAD group, one patient (5.6%) died of serious lung infection and eight (44.4%) experienced grade 3 or higher adverse events, while only one (5.6%) discontinued treatment in improved PAD group due to similar toxicity. Compared to PAD group, grade 3 or worse adverse events was significantly reduced in improved PAD group, the most common symptoms were leucopenia (33.3% vs 61.1%, P=0.086), thrombocytopenia (50.0% vs 61.1%), anaemia (27.8% vs 16.7%), infection (16.7% vs 50.0%, P=0.075), diarrhea (5.6% vs 33.3%, P=0.088), peripheral neuropathy(0 vs 27.8%, P=0.045).</p><p><b>CONCLUSION</b>The improved PAD regimen by changing bortezomib from intravenous administration to subcutaneous injection significantly reduced adverse events, improved the safety of clinical application of bortezomib without affecting curative effect, and had great progress.</p>

Pulmonary disease caused by nontuberculous mycobacteria after allogeneic hematopoietic stem cell transplantation--a case report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To report a case with pulmonary disease caused by nontuberculous mycobacteria (NTM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a literature review.</p><p><b>METHODS</b>Case report and literature review.</p><p><b>RESULTS</b>A patient with acute non-lymphocytic leukemia was treated by allo-HSCT. Her NTM lung disease developed after HSCT was successfully treated with a 3 antimicrobials combination of clarithromycin, levofloxacin and capreomycin for 10 months.</p><p><b>CONCLUSION</b>NTM infections are infrequent in allo-HSCT recipients and have a good clinical prognosis if correctly treated.</p>