Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

Avapritinib is effective for treatment of minimal residual disease in acute myeloid leukemia with t (8;21) and kit mutation failing to immunotherapy after allogeneic hematopoietic stem cell transplantation.

In patients with t(8;21) acute myeloid leukemia (AML) with recurrent measurable residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), pre-emptive interferon-α therapy and donor lymphocyte infusion are noneffective in 30%-50% of patients. Avapritinib is a novel tyrosine kinase inhibitor targeting KIT mutations. We retrospectively report about 20 patients with t(8;21) AML and KIT mutations treated with avapritinib after allo-HSCT with MRD and most failing to respond to immunotherapy. Reduction of RUNX1-RUNX1T1 after 1 month of treatment was ≥1 log in 12 patients (60%), which became negative in 4 patients (20%). In 13 patients who received avapritinib for ≥3 months, the reduction was ≥1 log in all patients, which became negative in 7 patients (53.8%). The median follow-up time was 5.5 (2.0-10.0) months from avapritinib initiation to the last follow-up. Three patients underwent hematologic relapse and survived. Among all 20 patients, RUNX1-RUNX1T1 transcripts turned negative in 9 patients (45%). The efficacy did not differ significantly between D816 and non-D816 KIT mutation groups. The main adverse effect was hematological toxicity, which could generally be tolerated. In summary, avapritinib was effective for MRD treatment in patients with t(8;21) AML with KIT mutations failing to respond to immunotherapy after allo-HSCT.

Cytokine profiling during conditioning in haploidentical stem cell transplantation and its prognostic impact on early transplant outcomes.

Cytokine storm development is a major cause of many transplant-related complications, especially during the conditioning regimen. This study aimed to characterize the cytokine profile and determine its prognostic impact during conditioning in patients undergoing subsequent haploidentical stem cell transplantation. A total of 43 patients were enrolled in this study. Sixteen cytokines associated with cytokine release syndrome (CRS) during anti-thymocyte globulin (ATG) treatment were quantified in patients undergoing haploidentical stem cell transplantation. Thirty-six (83.7%) patients developed CRS during ATG treatment; most of those cases (33/36; 91.7%) were classified as grade 1 CRS, whereas only three (7.0%) developed grade 2 CRS. CRS was observed more frequently on the first (15/43; 34.9%) and second day (30/43; 69.8%) of ATG infusion. No factors were identified that could predict the development of CRS on the first day of ATG treatment. Five of the 16 cytokines (interleukins 6, 8, and 10 (IL-6, IL-8, and IL-10), C-reactive protein (CRP), and procalcitonin (PCT)) were significantly elevated during ATG treatment, although only the level of IL-6, IL-10, and PCT were associated with the severity of CRS. However, neither CRS nor the cytokine levels significantly impacted the development of acute graft-versus-host disease (GVHD) or cytomegalovirus (CMV) infection or affected overall survival.

Comparison of therapeutic effects of arthroscopic popliteal cyst internal drainage and capsular wall resection / 中国骨伤

OBJECTIVE@#To investigate efficacy between arthroscopic popliteal cyst drainage and arthroscopic popliteal cyst resection.@*METHODS@#From January 2013 to June 2021, 54 patients with popliteal cyst (Rausching-Lindgren gradeⅠto Ⅲ) were treated with arthroscopic surgery. There were 24 males and 30 females. The age ranged from 44 to 72 years old, with a mean of (62.67±6.08) years old. The course of the disease ranged from 1 to 72 months, with a mean of(15±14) months. Twenty-four patients (group A) were underwent arthroscopic internal drainage of popliteal cyst. Thirty patients (group B) were underwent arthroscopic resection of popliteal cyst. Preoperative main symptoms included knee pain, swelling, walking pain, popliteal swelling, popliteal mass and so on. After 1, 3, 6 months and 1, 2 years of surgery, routine outpatient follow-up was conducted to observe and compare the surgical time, bleeding volume, preoperative and postoperative visual analog scale (VAS), knee Lysholm score, and complications between two groups.@*RESULTS@#All incisions healed at one stage after operation. All 54 patients were followed up, and the duration ranged from 6 months to 2 years, with an average of (13.89±4.29) months. There was no intraoperative vascular or nerve injury. Operation time and intraoperative blood loss of the two groups:group A of (62.08±9.55) min and (8.00±1.69) ml, group B of (69.50±6.99) min and (8.70±2.00) ml. Popliteal pain, swelling, limitation of flexion and extension were significantly relieved after operation. VAS before and one month after operation between two groups:group A of 5.38±1.21 and 2.63±0.71, group B of 5.60±1.26 and 2.80±0.81. Lysholm scores of knee joint before and 6 months after operation:group A of 62.59±4.99 and 89.74±2.90, group B of 63.87±3.23 and 89.02±2.35. Knee joint function improved significantly in both groups. In group A, 4 cases had popliteal cyst at 3 months after operation, and 2 cases had small isolated cyst at 1 year after operation. There was no recurrence of cyst in group B.@*CONCLUSION@#The results between two arthroscopic treatments of popliteal cyst are satisfactory, and there is no significant difference in the amount of blood loss, safety, postoperative pain VAS score and knee function recovery. It is suggested that arthroscopic resection of the cyst wall should be performed when the technique is mature, especially for large cysts and septal cysts.

Locking compression plate combined with medial buttress plate for the treatment of osteoporotic comminuted proximal humerus fractures / 中国骨伤

OBJECTIVE@#To explore clinical effect of lateral locking compression plate combined with medial buttress plate in treating osteoporotic comminuted fractures of proximal humerus.@*METHODS@#From May 2017 to December 2021, 12 patients with osteoporotic comminution of proximal humerus were treated by lateral locking compression plates combined with medial buttress plates, including 5 males and 7 females, aged from 55 to 78 years old, bone mineral density(BMD) less than -2.5 g/cm3, the time from injury to operation was from 2 to 6 days. According to Neer classification, 7 patients were type Ⅲ, 4 patients were type Ⅳ and 1 patient was type Ⅵ. Postoperative complications, fracture healing and internal fixation were observed and Constant-Murley score of shoulder joint was used to evaluate clinical effects at 6 months after operation.@*RESULTS@#Postoperative wound healed well at stage I. All patients were followed up from 6 to 18 months. Humeral head collapse and necrosis occurred in 1 patient and humeral head varus in 1 patient. No impact of shoulder joint, internal fixation loosening occurred. Constant-Murley score at 6 months ranged from 45 to 90 points, and 6 patients got excellent result, 3 good, and 3 poor.@*CONCLUSION@#Locking compression plate combined with medial buttress plate could effectively reconstruct medial humeral column support and enhance fracture stability, and receive satisfactory clinical results. However, no control group was established in this study, and function of shoulder joint has not been evaluated many times after operation, so it cannot dynamically reflect changes of shoulder joint function.

Haploidentical- versus identical-sibling transplant for high-risk pediatric AML: A multi-center study.

BACKGROUND: Human leukocyte antigen-identical sibling donor (ISD)-hematopoietic stem cell transplantation (SCT) is a potentially curative treatment for high-risk pediatric acute myeloid leukemia (AML). A haploidentical donor (HID) is readily available to almost all children. Previous studies have demonstrated that patients with HID-SCT had similar outcomes compared to ISD-SCT for pediatric and adult AML. However, the role of HID-SCT in high-risk pediatric AML is unclear. METHODS: To compare the overall survival of high-risk AML children who underwent either HID-SCT or ISD-SCT, we analyzed 179 cases of high-risk AML patients under 18 years of age treated with either ISD-SCT (n = 23) or HID-SCT (n = 156). Granulocyte colony-stimulating factor plus anti-thymocyte globulin-based regimens were used for HID-SCT. We also analyzed the subgroup data of AML patients at first complete remission (CR1) before SCT with known cytogenetic risk. RESULTS: The numbers of adverse cytogenetic risk recipients were 8 (34.8%) and 13 (18.8%) in the ISD-SCT group and the HID-SCT group, and the number of patients with disease status beyond CR1 were 6 (26.1%) and 14 (20.3%) in the two groups. The cumulative rates of grades II-IV acute graft-versus-host disease (GVHD) were 13.0% in the ISD-SCT group and 34.8% in the HID-SCT group (P = 0.062), with a three-year cumulative rates of chronic GVHD at 14.1% and 34.9%, respectively (P = 0.091). The relapse rate in the ISD-SCT group was significantly higher than that in the HID-SCT group (39.1% vs. 16.4%, P = 0.027); with non-relapse mortality at 0.0% and 10.6% (P = 0.113), respectively. The three-year overall survival rates were 73.0% for the ISD-SCT group and 74.6% for the HID-SCT group (P = 0.689). In subgroup analysis, the three-year relapse rate in the ISD-SCT group was higher than that in the HID-SCT group (50.0% vs. 9.2%, P = 0.001) and the three-year DFS in the ISD-SCT group (50.0%) was lower than that in the HID-SCT group (81.2%) (P = 0.021). CONCLUSIONS: Unmanipulated HID-SCT achieved DFS and OS outcomes comparable to those of ISD-SCT for high-risk pediatric AML patients with potentially higher rate but manageable GVHD.

Modified osteotomy of olecranon for the management of inter-condylar fracture of the humerus / 中国骨伤

<p><b>OBJECTIVE</b>To explore the surgical method and clinical outcome of modified osteotomy of olecranon for the treatment of inter-condylar fracture of humerus.</p><p><b>METHODS</b>From May 2007 to December 2012, 32 patients of intercondylar fracture of humerus were treated surgically through the approach of modified osteotomy of olecranon. The patients were 21 males and 11 females with a mean age of 46.3 years (ranged 18 to 65 years). Nineteen fractures occurred on the right extremity and 13 on the left extremity. According to the AO classification, type C1 fracture was found in 7, C2 in 11 and C3 in 14. Five patients suffered from open fracture (Gustilo type Iin 3, type II in 2). Other fractures occurred in 6 patients and the primary injury of nerve occurred 6. The healing of the osteotomy was evaluated with physical examination and plain X-ray film, and the function of elbow was assessed according to Cassebaum scale.</p><p><b>RESULTS</b>All the patients were followed from 9 months to 5 years(average, 1.9 years). All the osteotomies healed at 7.4 weeks averagely after operation, and no nonunion, delayed union, fracture of ulna olecranon were found. Two cases had little pain on the elbow, heterotopic ossification occurred in 2 cases and cutting bone block loosed in 1 case. The function of the elbow showed excellent in 19 cases, good in 8, fair in 4 and poor in 1.</p><p><b>CONCLUSIONS</b>The use of the approach of modified olecranon osteotomy for surgical management of intercondylar fracture of humerus has some advantages, it provides satisfactory stability with simple technical procedures avoiding inter-articular invasion, and it facilitates rehabilitation exercises and providing good results with low complication rates.</p>

Modified Stoppa approach in treatment of bilateral pubic branch fractures / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the feasibility and effectiveness of modified Stoppa approach in treatment of bilateral pubic fractures of pelvic.</p><p><b>METHODS</b>The therapeutic effects of 16 patients with bilateral pubic fractures treated through the modified Stoppa approach from January 2010 to January 2014 were summarized and analyzed, involved 11 males and 5 females with an average age of 40.5 years old ranging from 17 to 59 years. According to Tile classification, there were 8 patients with type A, 6 with type B and 2 with type C. For 16 pelvic fractures, the modified Stoppa approach was used exclusively 11 cases, in combination with the iliac fossa approach in 4 cases, and in combination with the posterior approach in 1 case. The operation incision length, operation time , intra-operative blood loss and postoperative complications were observed. The fracture reduction and post-operative function were assessed by Matta criteria and Majeed system respectively.</p><p><b>RESULTS</b>The incision length of the modified Stoppa approach ranged from 8 to 10 cm (averaged in 9 cm). The operation time ranged from 75 to 135 minutes (averaged in 95 minutes). The intra-operative blood loss ranged from 400 to 900 ml (averaged in 600 ml). Sixteen patients were followed up from 7 to 18 months (averaged in 12.5 months). The fractures were all healed, the fracture healing time was 2.7 to 5 months (means 3.1 months). There were no infections, ectopic ossification, screw loosening, plate breakage and lateral ventral syndrome. According to Matta criteria for pubic fracture reduction, the result was excellent in 9 cases, good in 6, fair in 1. The Majeed function scores at 6 months after operation was 85.32±8.50; the result was excellent in 8 cases, good in 6 cases, fair in 2 cases.</p><p><b>CONCLUSION</b>The modified Stoppa approach has characteristics of convenience and directness of incisions, clear operation field, easy reduction, few complications and fast recovery , it is an ideal choice in surgical treatment of bilateral pubic fractures.</p>

Locking plate external fixator for the treatment of middle and distal tibial fractures / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the effectiveness of locking plate external fixator in treating middle and distal tibial fractures.</p><p><b>METHODS</b>From January 2010 to January 2013,18 patients suffered from middle and distal tibial fractures were treated by locking plate external fixator,including 11 males and 7 females, with an average age of 53.5 (ranged from 13 to 80) years old,the course of disease ranged from 2 h to 3 d. According to AO classification, 4 cases were type A,11 cases were type B and 3 were type C. Among them,6 patients were open fracture, including 2 cases with type I, 3 cases with type II and 1 case with type III, according to Gustilo classification), 12 patients were close fracture. Operation time, postoperative complications were observed, and Johner-Wruhs scoring were used to evaluate clinical outcomes.</p><p><b>RESULTS</b>All patients were followed up from 6 to 15 (meaned 11) months. Two cases occurred skin necrosis (1 case occurred bone exposure), 2 cases occurred delayed union (all were open fracture), and 1 case occurred nail infection. No screw loosening or broken occurred. According to Johner-Wruhs scoring, 10 cases obtained excellent result,6 cases good,and 2 cases fine.</p><p><b>CONCLUSION</b>Locking plate external fixator for the treatment of middle and distal tibial fractures, which has advantages of lessen damage, shorter operative time, less complications and rapid functional recovery, is one of good choice.</p>

[Molecular characterization and phylogenetic analysis of porcine epidemic diarrhea virus field strains in central China during 2010-2012 outbreaks].

Since late 2010, porcine epidemic diarrhea virus (PEDV) has been re-emerging in central China. To explore the possible reason of the PEDV outbreaks, twelve PEDV field strains were isolated from different swine breeding farms in central China during 2010-2012, and molecular diversity, phylogenetic relationships of these strains with other PEDV reference strains were investigated. Sequence analysis of S, M and ORE3 genes revealed that the central China PEDV isolates had several specific nucleotides and amino acids which were different from PEDV reference strains. In addition, the entire S genes of eleven central China PEDV isolates were found to be nine nucleotides longer in length than CV777 and large number of amino acid variations was accumulated in the N-terminal region of S gene. Phylogenetic analysis showed that the central China PEDV isolates had close relationship with Korea strains (2007-2009), Thailand strains (2007-2008), Vietnam strains (2009-2010), Japan strains (2010), and other prevailing strains from other parts of China (2010-2012). However, they differed genetically from European strains (CV777, Brl/87), China strains (2003-2007) and the vaccine strains (CV777) used in China. These results imply that a rapid variation and evolution of central China PEDV strains has occurred in recent years, and a more efficient vaccine strain should be selected to prevent and control outbreaks of PEDV in China.

Genetic variation analysis of reemerging porcine epidemic diarrhea virus prevailing in central China from 2010 to 2011.

Porcine epidemic diarrhea has re-emerged with devastating impact in central China since October 2010. To investigate and analyze the reason of this outbreak, the M and ORF3 genes of 15 porcine epidemic diarrhea viruses (PEDV), which were collected from different areas of central China during October 2010 and December 2011, were amplified by reverse transcriptase polymerase chain reaction, cloned, sequenced, and analyzed. Sequence analyses showed that the nucleotides and amino acids were changed at some sites in the M and ORF3 genes of the 15 PEDV strains compared with those genes of CV777 reference strain. Based on the phylogenetic analyses, PEDVs in central China and reference strains could be separated into three groups: G1, G2, and G3. The 15 PEDV strains belonged to G3 group and showed a close relationship with Korean strains (2007), Thai strains (2007-2008), and partial other Chinese strains (2010-2011), but differed genetically from European strains (Br1/87) and the vaccine strain (CV777 vs) being used in China. Furthermore, all 15 PEDV strains from central China and some other isolates in China from 2003 to 2007 (LJB-03, QH, and LZC) belonged to different group. Therefore, PEDV exhibits rapid variation and genetic evolution, and the currently prevailing PEDV strains in central China are a new genotype.

Reversed sural neurovascular fasciocutaneous flap for reconstruction of soft tissue defects of lower limbs / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the clinical application of the reversed sural neurovascular fasciocutaneous flap.</p><p><b>METHODS</b>From January 2007 to May 2009,10 patients (6 males and 4 females) with soft tissue defects on lower limbs were treated by reversed sural neurovascular fasciocutaneous flap. The end-to-side neuroanastomosis were used to reinnervate the flap and microsurgery was used for anastomosing small saphenous vein. The age ranged from 16 to 55 years (mean, 32 years). There were 6 patient with soft tissue defects on foot, 2 patients with exposed bone after operation, 2 patients with chronic ulcer on limb. The patients were evaluated with appearance, blood supply, texture and 2-PD of the flaps.</p><p><b>RESULTS</b>All the patients were followed for 6 to 24 months (mean, 15 months). The flaps in all 10 patients survived completely. The appearance, blood supply and texture of the flaps were excellent and 2-PD was 9 to 12 mm.</p><p><b>CONCLUSION</b>This flap has sufficient blood supply and high survival rate. It also effectively retains the feeling of dorsolateral heeland improved quality of life.</p>

Surgical treatment of tibia plateau fractures with external fixator and the locking plate / 中国骨伤

<p><b>OBJECTIVE</b>To observe the clinical effect of the treatment for complex fractures of the tibial plateau through the application of the external fixator and the locking plate.</p><p><b>METHODS</b>From Feb. 2006 to Oct. 2008,12 patients with tibial plateau fractures were treated with external fixator and locking plate included 8 males and 4 females with an average age of 38 years ranging from 23 to 59. According to Schatzker type, 7 cases were type V and 5 cases were type VI. Using an anteromedial incision and an anterolateral approach, the locking plate were fixed in the tibia lateral. The collapse and height lossing of tibial plateau was observed through X-ray film before and after operation. The function of knee joint was evaluated according to HSS scoring.</p><p><b>RESULTS</b>These patients were followed up for 4 to 18 months (means 9.79 months). Eleven cases had bone primary union,and 1 delayed union. No deep phlebothrombosis and osteofascial compartment syndrome occurened. The average healing time was 3.1 months. Between the preoperative and postoperative X-ray film there were no second stage depression fracture of the tibial plateau,postoperative reduction loss and bad alignment. The range of knee flexion was 90 degrees to 110 degrees. The HSS knee functional scoring was(75.50 +/- 10.01)scores after operation and (21.50 +/- 11.68) scores before operation.</p><p><b>CONCLUSION</b>The treatment with the external fixator and the locking plate for complex fractures of the tibial plateau could provid continuous stability of fixation,prevent the fracture from second stage displacement and the knee force line change, protect the soft-tissue around the knee, reduce the postoperative complications. The knee joint function is satisfied.</p>