Feasibility of HLA-haploidentical hematopoietic stem cell transplantation between noninherited maternal antigen (NIMA)-mismatched family members linked with long-term fetomaternal microchimerism

Based on the hypothesis that long-term fetomaternal microchimerism is associated with acquired immunologic hyporesponsiveness to noninherited maternal antigens (NIMAs) or inherited paternal antigens (IPAs), several groups have recently reported successful cases of non-T-cell-depleted hematopoietic stem cell transplantation (SCT) from HLA-haploidentical family members mismatched for NIMAs. In this study, we examined the outcomes of 35 patients with advanced hematologic malignancies who underwent HLA-2-antigen- or HLA-3-antigen-incompatible SCT from a microchimeric NIMA-mismatched donor. After standard-intensity or reduced-intensity preparative regimens, all patients had sustained hematopoietic recovery with tacrolimus-based graft-versus-host disease (GVHD) prophylaxis. Grade II/IV acute GVHD occurred in 19 (56%) of 34 evaluable patients, while extensive chronic GVHD developed in 13 (57%) of 23 patients who could be evaluated. Multivariate analysis demonstrated that NIMA mismatch in the GVH direction was associated with a lower risk of severe grade III-IV acute GVHD when compared with IPA mismatch (P = .03). Fifteen patients were alive and 14 of them were disease-free with a median follow-up of 20 (range, 8 to 37) months. These results indicate that T cell-replete SCT from an HLA-haploidentical NIMA-mismatched donor can offer durable remission with an acceptable risk of GVHD in selected patients with advanced hematologic malignancies who lack immediate access to a conventional stem cell source.     

Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell-depleted reduced-intensity transplantation

Allogeneic hematopoietic stem cell transplantation (SCT) regimens incorporating the lymphocytotoxic CD52 antibody alemtuzumab demonstrate efficient engraftment and reduced graft-versus-host disease (GVHD). However, these protocols substantially impair posttransplantation antiviral and antitumor immunity. To accelerate immune reconstitution after alemtuzumab-based reduced-intensity SCT, we administered prophylactic CD8-depleted donor lymphocyte infusions (DLIs) starting on days 60 and 120 after transplantation. DLIs were processed in an immunomagnetic good manufacturing practice depletion procedure resulting in a 2.5- to 6-log reduction in CD8 T cells. Of 23 high-risk patients with hematologic malignancies, 11 received a total of 21 CD8-depleted DLIs. Five patients developed transient grade I acute GVHD following transfer. Only 2 patients with HLA-C-mismatched donors showed grade II and III acute GVHD and subsequently progressed to limited chronic GVHD. Following DLIs, 4 patients with declining hematopoietic donor chimerism converted to full chimeras. A 2.1-fold median increase of circulating CD4 T cells was observed within 2 weeks after infusion. Non-DLI patients did not show a comparable rise in CD4 counts. Four patients demonstrated enhanced frequencies of cytomegalovirus-specific CD4 and CD8 T cells following transfer. Our results suggest that prophylactic CD8-depleted DLIs accelerate immune reconstitution after lymphodepleted HLA-matched SCT and carry a low risk of inducing severe GVHD.     

Pancreatic Hyperamylasemia and Hyperlipasemia in Association with Cytomegalovirus Infection Following Unrelated Cord Blood Transplantation for Acute Myelogenous Leukemia

Cytomegalovirus (CMV)-associated pancreatitis is rare after allogeneic hematopoietic stem cell transplantation (SCT). We describe a patient who developed pancreatic hyperamylasemia and hyperlipasemia in association with CMV infection after cord blood transplantation (CBT). A 31-year-old man with acute myelogenous leukemia underwent CBT. A neutrophil count consistently greater than 500/microL was achieved on day +21. Positive results for CMV antigenemia on days +35 and +67 prompted 2 courses of preemptive therapy with ganciclovir or foscarnet. The CMV antigenemia value again became positive on day +134. On day +141, serum amylase and lipase activities markedly increased to 1221 IU/L and 894 IU/L, respectively. The patient had no abdominal symptoms. Ultrasonography and computed tomography results showed no abnormalities of the pancreas. A diagnosis of possible pancreatitis was made. After the initiation of foscarnet therapy, the CMV antigenemia results soon became negative, and serum amylase and lipase activities returned to normal. Therefore, CMV infection was considered to play a major role in the development of pancreatic hyperamylasemia and hyperlipasemia in our patient. The present report indicates that CMV infection should be included in the differential diagnosis for patients with pancreatic hyperamylasemia after SCT.     

Efficacy of folinic acid in preventing oral mucositis in allogeneic hematopoietic stem cell transplant patients receiving MTX as prophylaxis for GVHD

As the safety of folinic acid administration and its efficacy for reducing the toxicity of MTX remain controversial, we assessed the effect of folinic acid administration after MTX treatment for GVHD prophylaxis on the incidence of oral mucositis and acute GVHD. We retrospectively analyzed data for 118 patients who had undergone allogeneic hematopoietic SCT and had received MTX for GVHD prophylaxis. Multivariate analysis showed that systemic folinic acid administration significantly reduced the incidence of severe oral mucositis (odds ratio (OR)=0.13, 95% confidence interval (CI) 0.04-0.73, P=0.014). There was also a tendency for a lower incidence of severe oral mucositis in patients who received folinic acid mouthwash (OR=0.39, 95%CI 0.15-1.00, P=0.051). No significant difference was observed in the incidence of acute GVHD between patients who received systemic folinic acid administration and those who did not (P=0.88). Systemic folinic acid administration and mouthwash appear to be useful for reducing the incidence of severe oral mucositis in patients who have received allogeneic hematopoietic SCT using MTX as GVHD prophylaxis.     

MxA expression in patients with viral infection after allogeneic stem cell transplantation

Many patients suffer febrile diseases soon after allogeneic stem cell transplantation (SCT). Some of the symptoms of viral infections and acute GVHD are often difficult to distinguish. However, an accurate diagnosis is important since the treatments for these conditions are different. It is known that MxA protein is specifically induced in patients with several viral infections. We investigated the cytoplasmic expression of MxA in the peripheral blood mononuclear cells (PBMCs) of patients with fever after allogeneic SCT using a newly generated monoclonal antibody (KM1135) and flow cytometry. The level of MxA expression was significantly higher in patients diagnosed with viral infections (n=6, cytomegalovirus in three, Epstein-Barr virus in one, human herpesvirus-6 in one, adenovirus in one) than control individuals (n=9) (P<0.05, Mann-Whitney test). The level of MxA in patients with aGVHD (n=7) was identical to that in controls. The level of MxA correlated well with the amount of the cytomegalovirus antigen-positive cells in the presence of acute GVHD in two patients. The measurement of MxA is simple and useful in distinguishing viral disease from acute GVHD after allogeneic SCT.     

Circulating IL-17 levels during the peri-transplant period as a predictor for early leukemia relapse after myeloablative allogeneic stem cell transplantation

IL-17 is involved in inducing and mediating pro-inflammatory responses. The association of IL-17 with tumor growth or graft-versus-host disease (GVHD) has become a subject of controversy. We hypothesized that serum IL-17 (sIL-17) levels during the peri-transplant period may affect alloreactive responses after allogeneic stem cell transplantation (SCT). sIL-17 levels of 95 patients with leukemia who had undergone myeloablative allogeneic SCT were measured using ELISA before conditioning and on day?0, +7, and +14 after transplantation. With a median follow-up of 17?months, the overall survival, disease-free survival, non-relapse mortality, and relapse incidence were 70.9%, 66.3%, 10.3%, and 23.4%, respectively. Ten patients relapsed within 180?days (early relapse, 10.5%) post-transplant. The cumulative incidence of acute GVHD over grade II and chronic GVHD was 55.8% and 69.0%, respectively. Analyses using repeated measures of ANOVA and mean values of sIL-17 revealed that patients relapsed within 180?days had higher sIL-17 levels, whereas no association existed between sIL-17 levels and other clinical outcomes, including acute GVHD. Receiver operating characteristic curve analyses also revealed that sIL-17 levels were available for the prediction of early relapse and that patients with higher sIL-17 levels at each time point had a significantly higher early relapse. Multivariate analyses and subgroup analyses with only standard disease status suggest the association of sIL-17 levels with subsequent early relapse independent of disease status at transplantation. This study is the first one demonstrating the early change in sIL-17 during the peri-transplant period and the association with early relapse in humans.     

Myeloablative allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: significant roles of total body irradiation and chronic graft-versus-host disease

Disease-free survival in Philadelphia chromosome-positive ALL (Ph + ALL) is very poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently considered the only procedure with curative potential. To identify factors affecting transplant outcome, we analyzed the data from 197 Ph + ALL patients aged 16 years or older who had undergone allo-HSCT. The 5-year survival rates were 34% for patients in first complete remission (CR), 21% for those in second or subsequent CR, and 9% for those with active disease (P < 0.0001). Multivariate analysis showed four pre-transplant factors as significantly associated with better survival: younger age, CR at the time of transplantation, conditioning with total body irradiation, and HLA-identical sibling donor (P < 0.0001, P < 0.0001, P = 0.0301, P = 0.0412, respectively). Severe acute GVHD increased the risk of treatment-related mortality (TRM) without diminishing the risk of relapse, whereas chronic GVHD reduced the risk of relapse without increasing the risk of TRM. Thus, patients who developed extensive chronic GVHD had better survivals (P = 0.0217), and those who developed grade III-IV acute GVHD had worse survivals (P = 0.0023) than did the others.     

Extracorporeal photochemotherapy in the treatment of severe steroid-refractory acute graft-versus-host disease: a pilot study

Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing agent 8-methoxypsoralen and UV-A radiation has been shown to be effective in the treatment of selected diseases mediated by T cells, rejection after solid organ transplantation, and chronic graft-versus-host disease (GVHD). We present 21 patients with a median age of 38 years who developed steroid-refractory acute GVHD grades II to IV after stem cell grafting from sibling or unrelated donors and were referred to extracorporeal photochemotherapy (ECP). Three months after initiation of ECP 60% of patients achieved a complete resolution of GVHD manifestations. Complete responses were obtained in 100% of patients with grade II, 67% of patients with grade III, and 12% of patients with grade IV acute GVHD. Three months after start of ECP complete responses were achieved in 60% of patients with cutaneous, 67% with liver, and none with gut involvement. Adverse events observed during ECP included a decrease in peripheral blood cell counts in the early phase after stem cell transplantation (SCT). Currently, 57% of patients are alive at a median observation time of 25 months after SCT. Probability of survival at 4 years after SCT is 91% in patients with complete response to ECP compared to 11% in patients not responding completely. Our findings suggest that ECP is an effective adjunct therapy for acute steroid-refractory GVHD with cutaneous and liver involvement. However, in patients with acute GVHD grade IV or gut involvement other therapeutic options are warranted.     

Serum amylase determination in the emergency department evaluation of abdominal pain.

We hypothesized that selective ordering of serum amylase in the emergency department (ED) is justified because (a) most patients with elevated amylase can be prospectively identified by characteristic clinical findings, and (b) the diagnosis of pancreatitis is usually predominantly based on clinical findings, since amylase is known to be neither sensitive nor specific for pancreatitis. The study population included 133 consecutive patients with a chief complaint of abdominal pain who had amylase drawn over a 2-week period at a university hospital ED. Patients with known major trauma were excluded. Emergency department and hospital charts were reviewed for selected clinical variables. The first part of our hypothesis was evaluated by comparing clinical characteristics of cases (elevated amylase) and controls; the second part was tested by comparing clinical findings and amylase in cases (patients diagnosed as having pancreatitis) and controls. We found that 17 patients with and 116 without elevated amylase were similar with regard to all clinical variables, and that no combination of findings could be used to predict elevated amylase. Amylase level was not predictive of an ultimate diagnosis of pancreatitis, which was, however, strongly related to classical clinical findings. Pancreatitis risk factors, epigastric pain and tenderness, radiation of pain to the back, and nausea and vomiting were each statistically more common in patients diagnosed as having pancreatitis (regardless of amylase) than in patients in whom pancreatitis was excluded despite elevated amylase; all patients diagnosed with pancreatitis had at least two of these. Thus, selective ordering of amylase on the basis of clinical characteristics fails to identify a large proportion of patients with elevated amylase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hematopoietic stem cell transplantation with busulfanthiotepa-cyclophosphamide conditioning for pediatric patients with high-risk acute lymphoblastic leukemia]

Twelve children with high-risk acute lymphoblastic leukemia underwent stem cell transplantation (SCT) with a conditioning regimen consisting of busulfan, cyclophosphamide and thiotepa. Eight of them underwent SCT while in complete remission (CR) and the other 4 while not in CR. Three children underwent HLA-matched related bone marrow transplantation (BMT), 7 HLA-matched unrelated BMT, 1 HLA one-locus-mismatched unrelated cord blood cell transplantation, and 1 autologous peripheral blood stem cell transplantation. Grade II-IV acute GVHD was observed in 3 of the 11 allo-SCT cases, while chronic GVHD was seen in 3 of 9 evaluable cases. None of the 12 cases showed thrombotic microangiopathy, and veno-occlusive disease (VOD) was observed in 3. Nine of the patients are alive and disease-free 6-45 months after diagnosis. The event-free survival rate at 3 years was 72.2% for the 12 patients, including 8 of the 9 who received SCT during CR, and 2 of the 4 who did so while not in CR. The other 3 patients died: 2 of disease progression and 1 of VOD with pneumonia. All of those who died had undergone unrelated BMT.     

Amylase creatinine clearance ratio after biliary surgery.

The amylase creatinine clearance ratio (ACCR) is considered to be a more sensitive index of acute pancreatitis than the serum amylase level. Serial ACCR estimations were undertaken in 25 patients undergoing an elective cholecystectomy. Using accepted criteria, 28% of these patients developed, in the postoperative period, biochemical evidence of pancreatic gland damage, although the serum amylase level remained normal. This raised ACCR was particularly noted in patients who had undergone an exploration of the common bile duct. The ACCR would appear to be a more sensitive index of pancreatic gland disruption secondary to biliary surgery than the serum amylase level.     

Tacrolimus-Related Encephalopathy following Allogeneic Stem Cell Transplantation in Children

Tacrolimus is a potent immunosuppressive drug widely used to prevent and treat graft-versus-host disease (GVHD) in stem cell transplantation (SCT). Among 49 patients receiving tacrolimus who underwent SCT from January 2000 to July 2003, 10 patients (20%) developed encephalopathy. The commonly observed symptoms were convulsions and drowsiness, and most patients complained of signal symptoms such as headache, nausea, and cortical blindness before onset. The most common abnormality on neuroimages was high-intensity lesions in white matter on magnetic resonance imaging T2-weighted or fluid-attenuated inversion recovery images. At onset, all patients were receiving treatment for acute GVHD (grade II/III) or extensive chronic GVHD and demonstrated an abrupt increase in blood pressure from baseline levels. The serum tacrolimus concentration was generally within acceptable levels at onset. Symptoms gradually improved in all patients when the blood pressure was lowered with antihypertensive medication, regardless of continued tacrolimus administration following a short-term suspension. The pathogenesis of tacrolimus-related encephalopathy is multifactorial, although refractory GVHD and a sudden increase in blood pressure seem to be major predisposing factors. Because the withdrawal of tacrolimus or switching to less potent anti-GVHD agents usually worsens the GVHD, the administration of tacrolimus should be managed by closely monitoring serum levels and controlling blood pressure.     

Differing impacts of pretransplant serum ferritin and C-reactive protein levels on the incidence of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Studies have suggested an association between pretransplant serum levels of ferritin and C-reactive protein (CRP) and complications of allogeneic hematopoietic stem cell transplantation (HSCT). To evaluate the prognostic impact of these biomarkers on the development of acute and chronic graft-versus-host disease (GVHD), we retrospectively studied 211 patients who underwent allogeneic HSCT for hematologic diseases at our institution. The cumulative incidence rate of chronic GVHD at 3 years was 40.7 %. In the multivariate analysis, elevated CRP levels (≥2 mg/L) were significantly associated with a high incidence of chronic GVHD, whereas high ferritin levels (≥880 ng/mL) showed a tendency, though not statistically significant, to association with a low incidence of chronic GVHD. No significant association was observed between the pretransplant serum ferritin or CRP levels and the incidence of acute GVHD. Multivariate analysis indicated that high pretransplant serum ferritin levels were significantly associated with increases in treatment-related mortality and relapse rates. Overall, an elevated pretransplant serum ferritin level, but not an elevated serum CRP level, is a strong risk factor for overall mortality (hazard ratio, 2.16; P = 0.002). Our results also indicate that pretransplant serum CRP levels may be a useful biomarker for predicting the risk of chronic GVHD.     

Nutritional support for patients suffering from intestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

BACKGROUND: Patients who exhibit gastrointestinal (GI) involvement due to graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (SCT) are often recommended to withhold oral intake (NPO) to avoid further damage to the GI mucosa. However, it is possible that continuing oral intake could be beneficial in many patients compared to total parenteral nutrition (TPN). OBJECTIVE: The primary objective of this prospective study was to evaluate whether programmed step-ladder oral dieting (enteral nutrition; EN) is feasible and beneficial for these patients. METHODS: A total of 18 patients who exhibited GI-acute GVHD (stage I to III gut GVHD) after SCT received an EN dieting program, and changes in clinical and laboratory parameters were compared to those in a control cohort of 17 patients who were placed on NPO with TPN. Patients with GVHD were included prospectively and those with intestinal bleeding/obstruction, severe pancreatitis, and cytomegalovirus enterocolitis were excluded. RESULTS: None of the patients in the EN group experienced significant adverse events, including exacerbation of GI symptoms. Although there was no statistically significant difference in the volume or frequency of diarrhea or the time to complete dietary recovery, parameters including body weight and serum levels of total protein and albumin tended to improve faster in the EN group. CONCLUSION: The EN diet is safely applicable to patients suffering from GI involvement by GVHD.     

Serum levels of cytokines correlate to donor chimerism and acute graft-vs.-host disease after haematopoietic stem cell transplantation

BACKGROUND: Some patients become full donor chimeras (DC) early after stem-cell transplantation (SCT), while others remain mixed chimeras for a longer time. Little is known about the mechanism behind these phenomena. METHODS: Serum cytokine levels during conditioning and during the first month after SCT were analysed in 30 patients. Of the 21 patients who became full T-cell DC from the first analysed sample, 12 developed grade II-IV acute graft-vs.-host disease (GVHD) and the other nine, mild or no acute GVHD. Another nine patients were T-cell mixed chimeras (MC). All MC patients had no or mild acute GVHD. RESULTS: During the pretransplant conditioning, DC patients had higher levels of tumour necrosis factor (TNF)-alpha and lower levels of transforming growth factor (TGF)-beta and interleukin (IL)-10, compared with MC patients. During the first week after SCT, lower levels of TGF-beta and IL-10 and higher levels of soluble Fas (sFas) were found in DC patients compared with MC patients. During the second and third weeks after SCT, increased levels of TNF-alpha, interferon (IFN)-gamma and sFas were found among DC patients compared with MC patients. Patients who developed moderate-to-severe acute GVHD had higher levels of TNF-alpha, IFN-gamma, IL-10 and sFas at 2 weeks post-SCT than in those with less GVHD. Patients homozygous for the TNFd microsatellite alleles 3 or 4 had significantly higher TNF-alpha levels during conditioning and more often developed acute GVHD grades II-IV. CONCLUSION: These results indicate that an imbalance between pro-inflammatory and immune- modulating cytokines are involved in the development of chimerism and acute GVHD after allo-SCT. The Fas/FasL pathway is probably involved in the elimination of recipient cells leading to full donor chimerism.     

Carboxylic ester hydrolase: a serum marker of acute pancreatitis

By use of an enzyme-linked immunosorbent assay we established serum reference values of carboxylic ester hydrolase, a pancreatic secretory lipolytic enzyme, and explored to see if a raised serum level is indicative of acute pancreatitis. Postoperative elevation of carboxylic ester hydrolase was observed in seven out of ten patients who underwent pancreatic surgery. Serum levels of carboxylic ester hydrolase and amylase were determined in 129 patients admitted due to abdominal emergency conditions. Amylase was elevated in 27 patients, and in 20 of these raised carboxylic ester hydrolase levels affirmed the diagnosis acute pancreatitis. In five out of the seven patients with elevated amylase alone no etiologic factor of acute pancreatitis was found. Another 11 patients had raised carboxylic ester hydrolase levels without concomitant elevation of amylase. In all these patients, a likely cause of pancreatic inflammation was identifiable. Hence, a raised carboxylic ester hydrolase level, even in presence of normal amylase, could be indicative of acute pancreatic inflammation.     

Polymyositis after donor lymphocyte infusion

Chronic graft-versus-host disease (GVHD) is a common long-term complication of allogeneic hematopoietic stem-cell transplantation (HSCT), and is responsible for morbidity, mortality and a decrease in quality of life of patients after SCT. Polymyositis, which usually co-occurs with other manifestations of GVHD, has previously been reported. However, polymyositis as the sole manifestation of chronic GVHD following donor lymphocyte infusion (DLI) is rare. We report a 30-year-old man with Hodgkin's lymphoma who developed acute polymyositis following treatment by DLI 4?months post-allogeneic HSCT. The patient developed fever and generalized myalgia 22?days after a single dose of DLI. Laboratory testing showed elevated muscle enzymes and myopathic abnormalities on electromyographic examination. Muscle biopsy showed features of acute polymyositis, with widespread foci of muscle fiber necrosis associated with infiltration of small mononuclear cells. Twenty-four hours after diagnosis, the patient developed a fatal ventricular arrhythmia. Cardiac involvement may occur in association with polymyositis, but usually occurs in elderly patients after several months of illness. The present case highlights the importance of systematic cardiac evaluation when a diagnosis of polymyositis is initially made to exclude this infrequent presentation of chronic GVHD characteristically associated with some HLA-DR haplotypes.     

Varicella-Zoster Virus Encephalitis in a Patient Undergoing Unrelated Cord Blood Transplantation for Myelodysplastic Syndrome—Overt Leukemia

Varicella-zoster virus (VZV) infection of the central nervous system (CNS) is rare after hematopoietic stem cell transplantation (SCT). Here, we describe the first patient who developed VZV encephalitis after cord blood transplantation (CBT). A 35-year-old man with myelodysplastic syndrome-overt leukemia underwent CBT. On day +23, a neutrophil count consistently greater than 0.5 x 10(9)/L was achieved. On day +42, 1 mg/kg per day of prednisolone therapy was initiated for grade III acute graft-versus-host disease (GVHD). Then, the dose of prednisolone was slowly reduced. For exacerbation of chronic GVHD, the dose of prednisolone was again increased to 1 mg/kg per day on day +231. On day +265, localized cutaneous zoster in the left thoracic region occurred, but soon resolved after acyclovir therapy. On day +309, he suddenly developed diplopia. Subsequently, right facial palsy and hearing impairment occurred. No skin rash was observed. Magnetic resonance imaging (MRI) scans revealed multifocal abnormal high-signal intensity in the CNS. A high level of VZV DNA was detected in a cerebrospinal fluid specimen. He was diagnosed with VZV encephalitis. Acyclovir was given intravenously for 40 days. Four months after the onset, the neurologic symptoms had incompletely resolved. MRI scans showed substantial resolution but with mild residual lesions. The present report indicates that VZV should be considered as a possible causative agent in patients who develop multifocal neurologic symptoms of the CNS after SCT.     

急性胰腺炎患者血淀粉酶变化和CT诊断的比较

目的探讨血淀粉酶的变化规律及其机制。方法本研究对确诊的172例急性胰腺炎(AP)患者随机分为3组,分别在发病≤12 h、12～24 h、48～72 h行CT和血淀粉酶检查。分析不同时间段CT和血淀粉酶检出率。结果 87.5%患者血淀粉酶在6～12 h升高;100%患者血淀粉酶在12 h以上升高。91.3%的患者在12～24 h之间CT检查发现胰腺炎症变化,但与发病大于48 h相比,无显著差异。12 h之内,血淀粉酶升高的阳性率高于CT诊断的阳性率(χ2=22.04,P<0.01)。48～72 h D级、E级检出率明显高于12 h之内和12～24 h之间的检出率。血淀粉酶随着轻症急性胰腺炎分级水平有上升趋势;随着重症急性胰腺炎分级水平有下降趋势。结论血淀粉酶升高的水平与胰腺炎的病情程度无明显相关性,推测其机制可能与胰腺微循环受损程度有关。     

Anti-host isohemagglutinin production is associated with a higher risk of acute GVHD in ABO-incompatible transplantation

We retrospectively analyzed the association between anti-host isohemagglutinin (IH) production and the development of acute GVHD. Of 189 patients who received minor or major/minor ABO-incompatible hematopoietic SCT (HSCT) at our hospital, 36 patients (19%) showed IH production. IH was detected before the onset of acute GVHD in 10, around the same time in 8, and after the onset of acute GVHD in 17 patients. The cumulative incidence of grade II-IV acute GVHD was significantly higher in the IH+ group compared with the IH- group (P<0.0001). The higher risk of acute GVHD that was associated with IH production occurred irrespective of human leukocyte Ag compatibility and donor type. Furthermore, the incidence of acute GVHD in the IH- group was comparable to that seen in major ABO-incompatible or -compatible HSCT. Our findings not only showed a strong association between IH production and acute GVHD development, but also suggested that IH production might be a useful predictor of subsequent acute GVHD after ABO-incompatible HSCT.