Pneumocystis jirovecii pneumonia in non-HIV-infected patients with acute leukemia after chemotherapy:A case report and literature review / 吉林大学学报(医学版)

Objective:To discuss the clinical characteristics of the Pneumocystis jirovecii pneumonia (PCP) in the non-HIV-infected blood disease patients, and to analyze its risk factors, treatment methods, prognosis and prevention measures.Methods:A female patient aged 18years old was confirmed as acute myeloid leukemia (AML) , and experienced dyspnea, chest congestion and hypoxaemia during the recovery period of hemogram after chemotherapy.The chest CT showed the bilateral lung diffuse ground glass density images.The patient had a dry cough and the oxygen saturation was gradually decreased to 75％5dafter antibacteriological treatment.A repeat chest CT showed enlarged diffuse ground glass density images on both lungs.Considering about the possibility of PCP, the patient received oral trimethoprim/sulfamethoxazole (TMP/SMX) 1g, once every 6h, in combination with caspofungin.Results:Two days later, the symptoms of the patients were not improved.The patient was transferred to ICU and was diagnosed PCP by bronchoalveolar lavage.The patient was switched to oral TMP/SMX2g, once every 8h, in combination with caspofungin.Meanwhile, the patient received bi-level positive airway pressure ventilation (Bipap) for the increased work of breathing.Five days later, the symptoms of the patients were improved and the Bipap was stopped.The patient got better and discharged 5dlater.The patient continuely received oral TMP/SMX 2g, once every 8hfor 36d.Conclusion:Prevention of PCP should be focused, in the non-HIV-infected blood disease patients receiving chemotherapy.Diagnosis of PCP should be considered in these patients without prevention who once have suspected clinical manifestation of PCP in non-granulocytic phase.Early empirical treatment of PCP and ICU management in the non-HIV-infected blood disease patients with acute respiratory failure are the keys to reduce death and improve the prognosis of PCP.

Therapy-related acute myeloid leukemia with inv(16) after treatment of Hodgkin lymphoma: report of one case and review of literature / 白血病·淋巴瘤

Objective To improve the recognition of therapy-related acute myeloid leukemia (t-AML). Methods One patient who was diagnosed as AML with inv (16) following treatment of Hodgkin lymphoma (HL) was reported. The pathomechanism, diagnosis, treatments and prognosis of t-AML were systematically studied by reviewing a series of literature. Results A 36-year-old female with a history of HL 2 years ago was diagnosed t-AML. Karyotype analysis demonstrated inv (16) and the fusion gene of CBFβ/MYH11 was positive by polymerase chain reaction (PCR). The fusion gene of CBFβ/MYH11 was still positive after receiving 3 courses of chemotherapy. The leukemia reached completely molecular biological remission after receiving haploidentical peripheral blood stem cell transplantation. The patient has now survived 1.5 years with leukemia free and in a good performance. Conclusions The t-AML is difficult to treat, but it is heterogeneous. Cytogenetics and molecular biology have important implications for the prognosis of t-AML. Currently, allogeneic hematopoietic stem cell transplantation is the only effective way to cure t-AML.

Effects of preexisting donor-specific HLA antibodies for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To investigate the effects of donor-specific HLA antibodies(DSA) for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT) and the feasible treatment for DSA.@*Methods@#HLA antibodies were examined using the Luminex-based single Ag assay for 92 patients who were going on haplo-SCT and the correlations of graft failure and DSA among the patients who had finished SCT were analyzed.@*Results@#Of the total 92 patients who were going on haplo-HSCT, sixteen (17.4%) patients were HLA Ab-positive, including six (6.5%) patients with antibodies corresponding to donor HLA Ags (DSA-positive). Among the patients who had finished the haplo-HSCT with conventional myeloablative conditioning regimen, the engraftment rate was significantly higher in DSA (-) patients than that in DSA (+) patients [92.3% (24/26) vs 25.0%(1/4), χ2=8.433, P=0.004] and DSA was the only factor relevant with graft failure in multiple-factor analysis [OR=12.0(95% CI 1.39-103.5), P=0.024]. Strategies to decrease antibody levels were taken for 4 patients, two were their first transplantations, and the other two patients were their second haplo-HSCT. Three of the four patients were HLA-I-DSA positive and had gained donor engraftment by means of donor platelet transfusions to decreased the level of DSA, the fourth patient with both HLA-I and HLA-II DSA also gained engraftment with the treatments of TBI, rituximab and donor platelet transfusion.@*Conclusion@#DSA is one of the key factors of graft failure in haplo-HSCT. Donors should be selected on the basis of an evaluation of HLA antibodies before transplantation. If haplo-HSCT from donors with DSA must be performed, then recipients should be treated for DSA to improve the chances of successful engraftment.

Comparison of outcomes of adult acute lymphoblastic leukemia patients underwent autologous and allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the outcomes of adult patients with acute lymphoblastic leukemia (ALL) who underwent autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>From Jan 2007 to Dec 2010, 106 adult ALL patients were retrospectively divided into two groups, 50 in auto-HSCT group and 56 in allo-HSCT group. Auto-HSCT group included 21 patients with high-risk, 46 patients in CR1 and 4 cases in CR2. All the 50 patients had negative minimal residual disease (MRD) prior to HSCT. Allo-HSCT group included 44 patients with high risk, 51 patients in CR1 and 5 cases in CR2, 15 patients with positive MRD before allo-HSCT. response, regulatory T cells (Treg), cytokines levels and treatment-related adverse effects were observed.</p><p><b>RESULTS</b>Of the total 106 patients, 29 patients relapsed at a medium follow-up of 22.9(0.8-63.3) months. The 3-year cumulative relapse rate (RR) was (29.9±8.0) % in auto-HSCT group and (32.7±6.8) % in allo-HSCT group. There were no significant differences in RR and overall survival (OS) between auto-HSCT and allo-HSCT groups, even of stratified risk groups. In standard risk group, 3-year OS was (77.1±13.2) % in auto-HSCT group and (90.9±8.7) % in allo-HSCT group (P=0.739). In high-risk group, 3-year OS was (68.7±10.8) % after auto-HSCT and (45.2±8.5) % after allo-HSCT (P=0.094).</p><p><b>CONCLUSION</b>Due to acceptable RR and OS, adult ALL patients with no MRD before HSCT showed favorable survival. Auto-HSCT may be a considerable choice for adult ALL patients with negative MRD when lacking of donors for allo-HSCT.</p>

Vascular endothelial injury induced by anti-endothelial cell antibody in allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To clarify the role of endothelial cells (ECs) injury induced by anti-endothelial cell antibody (AECA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Serum immunoglobulin (IgG) from allo-HSCT recipients were purified and incubated with human umbilical vein vascular endothelium (HUVEC) in vitro, then the functional changes and cell apoptosis were tested.</p><p><b>RESULTS</b>After incubation with AECA positive IgG, soluble adhesion molecules significantly elevated in culture supernatant. When concentration of IgG was 160, 320, and 640 μg/ml, concentrations of soluble intercellular adhesion molecule-1 in supernatant were statistically higher in AECA positive groups [(117.10 ± 12.82) vs (78.17 ± 4.90) pg/ml, (151.30 ± 15.35) vs (89.46 ± 6.02) pg/ml, (239.00 ± 32.53) vs (127.80 ± 13.86) pg/ml, P<0.01)]. When concentration of IgG was 40, 80, 160, 320, and 640 μg/ml, concentrations of soluble vascular cell adhesion molecule-1 in supernatant were also statistically higher in AECA positive groups [(38.51 ± 3.76) vs (24.78 ± 2.59) pg/ml, (61.34 ± 6.99) vs (38.20 ± 3.17) pg/ml, (135.60 ± 24.46) vs (63.73 ± 5.08) pg/ml, (221.30 ± 29.40) vs (112.80 ± 8.91) pg/ml, (420.90 ± 31.70) vs (224.40 ± 20.79) pg/ml, P<0.01]. Clotting activity factors also elevated in culture supernatant after incubation with AECA positive IgG. When concentration of IgG was 80, 160, 320, and 640 μg/ml, concentrations of von Willebrand factor were statistically higher in AECA positive groups [(19.51 ± 0.72) vs (17.17 ± 0.60) ng/ml, P=0.0193; (22.97 ± 1.18) vs (18.27 ± 0.61) ng/ml, (26.40 ± 1.54) vs (19.53 ± 0.70) ng/ml, (34.35 ± 1.60) vs (23.81 ± 0.92) ng/ml, P<0.01]. When concentration of IgG was 320 and 640 μg/ml, concentrations of thrombomodulin were statistically higher in AECA positive groups [(57.50 ± 4.50) vs (40.31 ± 4.39) pg/ml, P=0.0132; (59.18 ± 4.11) vs (38.84 ± 5.16) pg/ml, P<0.01]. However, inflammatory factors (IL-1β, IL-6, IL-8 and ANG2) were not statistically different in AECA positive and negative groups (P>0.05). Moreover, IgG from AECA positive samples did not change the proliferation or cell apoptosis.</p><p><b>CONCLUSION</b>AECA from allo-HSCT recipients dysregulates ECs' function in vitro, but do not induce apoptosis, which is valuable in the pathophysiology of graft-versus-host disease (GVHD) and other complications after allo-HSCT.</p>

Outcome analysis of alternative donor allogeneic hematopoietic cell transplantation in the treatment of 19 severe aplastic anemia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of alternative donor allogeneic hematopoietic stem cell transplantation (AD allo-HSCT) in the treatment of severe aplastic anemia (SAA).</p><p><b>METHODS</b>Retrospective analysis of the clinical data of 19 SAA patients received AD allo-HSCT from May 2003 to December 2012. Of them, 12 received haploidentical HSCT (haplo-HSCT), 7 received unrelated donor transplantation. The conditioning regimen was CY+ATG+Flu±Ara-C±Bu/Mel, the GVHD preventing regimen was MMF+MTX+CSA/FK506; the median reinfusion quantity of CD34+ was 3.10(2.11-4.38)×10⁶/kg in allo-BMT and 4.90(2.08-6.88)×10⁶/kg in allo-PBSCT.</p><p><b>RESULTS</b>Hematopoiesis reconstitution was achieved in all 19 patients. Twelve patients developed acute graft-versus-host disease (aGVHD), and 7 developed chronic GVHD (cGVHD). Graft rejection (GR) was occurred in one patient. The median follow-up time was 13(3-115) months. Thirteen patients survived, and the prospective 5-year overall survival rate is (67.5±11.0)%.</p><p><b>CONCLUSION</b>AD allo-HSCT can be used as an alternative therapy for SAA patients without HLA matched sibling donor.</p>