Decitabine for Relapsed Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine（DAC） for treating patients with acute lymphoblastic leukemia（ALL） who relapsed after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission（CR）, 1 achieved a partial remission（PR）, and 1 had no response（NR） after treatment at the latest follow-up（LFU）, the median survival was 11.2 months（range, 3.8–34, 7 months）. The 1-and 2-year overall survival（OS） rates were 50%（6/12） and 25%（3/12）, respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL（57.1% vs. 20%）. No aggravated flares of graft-versus-host disease（GVHD） were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.

Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation for Patients with Hematologic Malignancies

To investigate the therapeutic effects and associated complications of allogeneic peripheral blood stem cell transplantation （allo-PBSCT）, 40 patients with various malignant hematopoietic diseases received allo-PBSCT. The preparative regimens were based on BUCY2 or modified BUCY2, The acute graft-versus host disease （aGVHD） was prevented by cyclosporin A and shortterm MTX regimen in all patients. Two patients from donors with one fully mismatched HLA on DRB1 locus and 4 from unrelated donor also administered Zenapox （CD25 MAb） at dosage of 1 rag/ kg every day on the day before transplantation and day 4 after transplantation. These 6 patients were also treated with mycophenolate mofetil （MMF）. Transfusion of the donor cells： The median of the transfused nucleated cells was 5.38×10^8/kg and that of the CD34^＋ cells was 7.8×10^6/kg respectively. All the patients gained hematopoietic reconstruction except one who died of infection before engraftment. Seven patients got Ⅱ°-Ⅳ° aGVHD and the incidence was 17.5 %. Fourteen patients got cGVHD and the incidence was 53.8 % in the patients who survived over 6 months. Twenty-eight patients had fever or other characteristics of infection. The median follow-up time was 13.8 months. The incidence of transplantation related mortality （TRM） was 17.5 %and 2 patients relapsed （5.0 %）. It was concluded that allo-PBSCT can reconstruct hematopoiesis quickly and is a favorable therapeutic method for leukemia.

Low WT1 transcript levels at diagnosis predicted poor outcomes of acute myeloid leukemia patients with t(8;21) who received chemotherapy or allogeneic hematopoietic stem cell transplantation

Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy.This study aimed to evaluate the impact of Wilm tumor gene-1(WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase(C-KIT) mutations at diagnosis,and RUNXTRUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.Methods:Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation(allo-HSCT) were included.Patients who achieved remission,received two or more cycles of consolidation chemotherapy,and had a positive measureable residual disease(MRD) test result(defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive allo-HSCT.Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles.WT1 transcript levels and C-KIT mutations at diagnosis,and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.Results:Patients who had a C-KIT mutation had significantly lower WTl transcript levels than patients who did not have a C-KIT mutation(6.7%± 10.6%vs.19.5%± 19.9%,P < 0.001).Low WTl transcript levels(<5.0%) but not C-KIT mutation at diagnosis,a positive MRD test result after the second cycle of consolidation chemotherapy,and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients(hazard ratio[HR]= 3.53,2.30,and 11.49;95%confidence interval[CI]1.64-7.62,1.82-7.56,and 4.43-29.82;P = 0.002,0.034,and <0.001,respectively);these conditions were also independently associated with low leukemia-free survival(HR =3.71,2.33,and 5.85;95%CI 1.82-7.56,1.17-4.64,and 2.75-12.44;P < 0.001,0.016,and <0.001,respectively) and overall survival(HR = 3.50,2.32,and 4.34;95%CI 1.56-7.82,1.09-4.97,and 1.98-9.53;P = 0.002,0.030,and <0.001,respectively) in all patients.Conclusions:Testing for WTl transcript levels at diagnosis in patients with AML and t(8;21) may predict outcomes in those who achieve remission.A randomized study is warranted to determine whether allo-HSCT can improve prognosis in these patients.

Gut microbiome in allogeneic hematopoietic stem cell transplantation and specific changes associated with acute graft vs host disease

Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentially life-threatening complications,and one of the most serious complications is acute graft-versus-host disease(GVHD).During the last decades,DNA sequencing technologies were used to investigate relationship between composition or function of the gut microbiome and disease states.Even if it remains unclear whether these microbiome alterations are causative or secondary to the presence of the disease,they may be useful for diagnosis,prevention and therapy in aHSCT recipients.Here,we summarized the most recent findings of the association between human gut microbiome changes and acute GVHD in patients receiving aHSCT.

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.

A comparison of flow cytometry detection of minimal residual disease and chimerism kinetics in chronic lymphocytic leukemia patients after allogeneic hematopoietic stem cell transplantation

Determination of minimal residual disease (MRD) remains crucial for the follow-up after therapy in chronic lymphocytic leukemia (CLL) patients. Chimerism was assessed by short tandem repeat (STR)-PCR and single nucleotide polymorphisms (SNP)-PCR, and MRD by a multicolor flow cytometric approach in 12 consecutive patients with CLL after they received allogeneic stem cell transplantation (SCT). Overall, 11 patients achieved MRD flow negativity [10 had full donor chimerism (FDC) and one had mixed chimerism (MC)]. Only one patient remained with MRD flow positivity and displayed MC. Fifty-six samples were concomitantly studied by both chimerism and MRD flow. A significant correlation was observed between MRD flow data and chimerism in both PB and BM by using a mixed effect linear regression (p < 0.001). Flow cytometry approach of MRD can be easily combined with chimerism during the follow-up post-allogeneic SCT. Both techniques appeared complementary for guiding post-transplant immunomodulation.

Clinical Utility of Molecular Diagnosis of Blood Stream Infections in Allogeneic Hematopoietic Stem Cell Transplantation Recipients with Hematologic Malignancies

Blood stream infections (BSIs) are a serious problem in patients with hematologic malignancies receiving allogeneic hematopoietic stem cell transplantation (ASCT). We evaluated the clinical utility of molecular diagnosis for the management of BSIs in such patients. We prospectively performed a polymerase chain reaction (PCR) analysis of microbial DNA in blood samples from 10 consecutive patients with hematological malignancies at least once a week for one month after ASCT. In total, 51 and 54 samples were analyzed by bacterial and fungal PCR assays, respectively. Bacteria were detected in 24 samples from 8 patients by PCR, but in only 2 samples from one patient by blood culture. Notably, the bacteria detected in at least half of the 24 samples were considered to have originated from the oral cavity. Fungi were detected in 5 samples from 3 patients by PCR, but not by blood culture. Most cases with positive PCR results were manageable with empirical antimicrobial therapy without disclosure of DNA data. Our DNA analyses did not directly contribute to management of BSIs, but did provide valuable microbiological evidence for the patients. Additionally, oral management appears to require a critical re-evaluation to reduce the occurrence of BSIs in ASCT recipients.

Review of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in solid tumors excluding breast cancer

Solid tumors in adults constitute a heterogeneous group of malignancy originating from various organ systems. Solid tumors are not completely curable by chemotherapy, even though some subgroups are very chemo-sensitive. Recently, oncologists have focused on the use of allogeneic hematopoietic stem cell transplantation(alloHSCT) with reduced intensity conditioning(RIC) for the treatment of some refractory solid tumors. After the demonstration of allogeneic graft-versus-leukemia effect in patients with hematological malignancies who received allo-HSCT, investigators evaluated this effect in patients with refractory metastatic solid tumors. According to data from experimental animal models and preliminary clinical trials, a graft-versus-tumor(GvT) effect may also be observed in the treatment of some solid tumors(e.g., renal cell cancer, colorectal cancer, etc.) after allo-HSCT with RIC. The use of RIC regimens offers an opportunity of achieving full-donor engraftment with GvT effect, as well as, a reduced transplant-related mortality. Current literature suggests that allo-HSCT with RIC might become a choice for elderly and medically fragile patients with refractory metastatic solid tumors.

Ruxolitinib add-on in corticosteroid-refractory graft-vs-host disease after allogeneic stem cell transplantation:Results from a retrospective study on 38 Chinese patients

BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.METHODS We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation.Ruxolitinib was administered5-10 mg/d depending on disease severity,patient status,and the use of antifungal drugs.Overall response rate,time to best response,malignancy relapse rate,infection rate,and treatment-related adverse events were assessed.RESULTS The analysis included 10 patients with SR-aGVHD (gradeⅢ/Ⅳ,n=9) and 28patients with SR-cGVHD (moderate/severe,n=24).For the SR-aGVHD and SRcGVHD groups,respectively:Median number of previous GVHD therapies was 2(range:1-3) and 2 (1-4);median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo;median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo;and overall response rate was 100%(complete response:80%) and 82.1%(complete response:10.7%) with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0%and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus,and varicella-zoster virus,respectively,were 30.0%,10.0%,and 0%for the SR-aGVHD group and 0%,14.3%,and 7.1%for the SR-cGVHD group.CONCLUSION Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.

Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs.identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia

Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.

A HIGHER INCIDENCE OF RELAPSE FOR ACUTE LYMPHOCYTIC LEUKEMIA TREATED WITH ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION CONDITIONED WITH BU-CY_2 REGIMEN

Objective: To analyze long-term outcome in sixty leukemia patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) following busulfan and cyclophosphamide (BU-CY2) between 1994 and 2000. Methods: BU-CY2 was used as the conditioning regimen and allo-HSCT was performed for all patients. All the patients were followed-up until August 2001 or death. The leukemia-free survival, relapse and transplant-related mortality were discussed. Results: All 60 patients had sustained engraftment. Acute GVHD occurred in 22 out of 60 patients (36.7%), and the incidence of acute GVHD was 48% in the patients with CML, 30% in AML and 26.7% in ALL. 38 patients are still alive in continuous remission with a median follow-up of 30 months (range 12–84) and 22 patients have died. The main causes of death were acute GVHD in 3 patients, CMV-IP in 7 patients and relapse in 11 patients, the remaining one died of pulmonary infection. Among 11 patients who died of relapse, 8 patients with ALL relapsed in the early stage post transplant (8/15, 53.3%), relapse was observed in the remaining 3 patients with AML, and however, no relapse was observed in CML. The probability of disease-free survival at 3 years for CML. AML and ALL patients was 80%, 70% and 26.7%, respectively. Conclusion: This results suggests that BU-CY2 is an effective conditioning regimen in patients with AML and CML, resulting in a low relapse rate and high long-term survival rate, but not as effective in patients with ALL, with a higher incidence of relapse and therefore, not recommended for ALL patients.

CYTOMEGALOVIRUS INTERSTITIAL PNEUMONITIS FOLLOWING ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

Objective： To explore the risk factors and prophylaxis and treatment of cytomegalovirus interstitial pneumonitis （CMV-IP） after allogeneic peripheral blood stem cell transplantation （allo-PBSCT）. Methods： 43 patients who received allo-PBSCT were allocated to either a Gancyclovir（GCV）-prophylaxis group （n=19） or a non-GCV prophylaxis group （n=24）. A comparison was made of the incidence of CMV-IP in patients given or not given prophylactic gancyclovir. Results： 9 patients in non-GCV prophylaxis group developed late CMV-IP （P〈0.05）. Graft-versus-host-disease （GVHD） may be associated with a high risk of CMV-IP. 5 cases of CMV-IP were successfully treated with GCV, but 3 cases died of CMV-IP. The most common adverse event of GCV was neutropenia, but was reversible. Conclusion： CMV infection was a major cause of interstitial pneumonitis after allo-PBSCT, which correlated strongly with the severity of GVHD. Gancyclovir was shown to be effective in both prophylaxis and treatment of CMV-IP.

OMISSION OF DAY +11 METHOTREXATE DOES NOT APPEAR TO INFLUENCE INCIDENCE AND SEVERITY OF GRAFT-VERSUS- HOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

Objective: To explore the influence of omission of the day +11 dose of methotrexate (MIX) on the incidence and severity of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: From April 1997 to October 2002, 80 leukemia patients (46 men and 34 women aged from 12 to 56 years with a median age of 35) underwent allo-HSCT at our BMT unit. Among them, 58 patients received grafts from HLA-identical siblings, 8 from HLA one major antigen mismatched siblings and 14 from HLA-matched unrelated donors. All patients received a modified cyclosporine and short-course MTX regimen for GVHD prophylaxis, which included MTX 15 mg on day +1, and 10 mg on days +3 and +6 (MTX day +11 dose omitted) and cyclosporine given daily. Results: The overall incidence of grade I~IV acute GVHD was 57.5% (46/80 patients), with grade II~IV acute GVHD in 28 patients (35%) and grade III~IV acute GVHD in 7 patients (8.8%). Among 58 patients receiving grafts from HLA-identical siblings, 24 patients developed grade I~IV acute GVHD (41.4%), with grade II~IV acute GVHD in 13 patients (22.4%) and grade III~IV acute GVHD in 4 patients (6.9%). 2l out of 22 patients receiving grafts from HLA one major antigen mismatched siblings and HLA-matched unrelated donors developed grade I~IV acute GVHD (95.5%), with grade II~IV acute GVHD in 14 patients (63.6%) and grade III~IV acute GVHD in 3 patients (13.6%). Chronic GVHD occurred in 38 out of 56 evaluable patients (67.9%), with extensive form in 15 patients (26.8%) and limited form in 23 patients (41.1%). With a median follow-up of 960 days (range 180~1980 days), the probability of leukemia-free survival at 3 years was 61.3% for all patients. Conclusion: Our results suggest that the day +11 MTX can be omitted without a major deleterious effect on the incidence and severity of graft-versus-host disease after HLA-identical sibling transplantation as well as HLA one major antigen mismatched sibling and HLA-matched unrelated donor transplantation.

APPLICATION OF TWO-COLOR INTERPHASE FISH USING SEX PROBE IN ALLOGENEIC STEM CELL TRANSPLANTATION

Objective: To evaluate the significance of two-color interphase fluorescence in situ hybridization (FISH) using X and Y centromere probe in the engraftment estimation and minimal residual disease (MRD) monitoring after allogeneic stem cell transplantation (alloSCT). Methods: Samples from 12 cases patients in different periods after alloSCT were detected by interphase FISH. Results: All of the 12 patients were proved to obtain engraftment 22–35 days after alloSCT. While traditional karyotype showed as 100%XX or 100%XY invariably, FISH showed different percentages of donor original sex chromosome. Conclusion: Two-color interphase FISH is a more sensitive and simple test for engraftment evaluation and MRD monitoring post SCT, though, it can not entirely replace traditional karyotype analysis and gene detection by RT-PCR.

Rapid identification of the origin of hematopoietic cells after allogeneic hematopoietic stem cell transplantation for leukemia with DNA-fingerprinting

In order to rapidly identify the presence of hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation (AHCT) for leukemia, we developed a technique for amplifying human hypervariable minisatellite DNA by polymerase chain reaction (PCR) combined with digoxigenin-labeled locus-specific oligonucleotide hybridization. DNA fingerprinting by this technique was used as a specific genetic marker to determine the success rate of engraftment after AHCT in 7 patients with leukemia. Six of them gained evidence of engraftment. The results show that the minisatellite DNA fingerprinting is of high individual specificity and is valuable in confirming engraftment after AHCT, especially when the patient and the donor are HLA identical and of the same sex, and have the same ABO-Rh blood grouping. The advantages of this technique are that there is no contamination by radioisotopes, and its use is not restricted by the half ulife. It is simple and highly sensitive. Engraftment of donor’s hematopoietic cells can be determined as early as 15 d post-transplantation using 100 ng DNA of the patient. We conclude that this technique is highly specific and sensitive, and can rapidly provide in formation about the origin of the hematopoietic cells, thus being of value in guiding early therapeutic intervention in AHCT.

Reduced-intensity conditioning allogeneic stem cell transplantation in malignant lymphoma: current status

stem cell transplantation （allo-SCT） is a potential cure for patients with malignant lymphoma that is based on the graft-versus-lymphoma （GVL） effect. Myeloablative conditioning allo-SCT is associated with high mortality and morbidity, particularly in patients older than 45 years, heavily pretreated patients （prior hematopoietic stem cell transplantation or more than two lines of conventional chemotherapy） or patients affected by other comorbidities. Therefore, conventional allo-SCT is restricted to younger patients （〈50 to 55 years） in good physical condition. Over the last decade, allo-SCT with reduced-intensity conditioning （RIC-allo-SCT） has been increasingly used to treat patients with lymphoma. This treatment is associated with lower toxicity and substantial decrease in the incidence of transplant- related mortality, and has the potential to lead to long-term remissions. Therefore, patients who are not suitable to undergo conventional allo-SCT can benefit from the potentially curative GVL effects of allo-SCT. Although RIC-allo-SCT has improved the survival of lymphoma patients, high post-transplant relapse rates or disease progression mainly results in treatment failure. Thus, further improvement is clearly needed. The role and timing of RIC-allo-SCT in the treatment of lymphoma remains unclear. Therefore, more prospective studies should clarify the effectiveness of this method. In this article, we review the recent literature on RIC-alIo-SCT as a treatment for major lymphoma subtypes. Areas that require further investigation in the context of clinical trials are also highlighted.

Rare myeloid sarcoma/acute myeloid leukemia with adrenal mass after allogeneic mobilization peripheral blood stem cell transplantation

Myeloid sarcoma(MS)is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia(AML).This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission.A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010.After one month,bone marrow biopsy and aspiration confirmed the diagnosis of AML.Allogeneic mobilization peripheral blood stem cell transplantation was performed,with the sister of the patient as donor,after complete remission(CR)was achieved by chemotherapy.Five months after treatment,an adrenal mass was detected by positron emission tomography-computed tomography(PET-CT).Radiotherapy was performed for the localized mass after a multidisciplinary team(MDT)discussion.The patient is still alive as of May 2013,with no evidence of recurrent MS or leukemia.

Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation for Thymoma-associated Severe Aplastic Anemia: a Case Report

THYMOMA, a relatively rare epithelial neoplasm with unique clinical and pathologic features, is the most usual diagnosis for a mass located in the mediastinum. It is often associated withautoimmune disorders. The myastnema gravls ano pure red cell aplasia are the most common disorders, with the incidences of 40% and 5%, respectively, while the incidence of aplastic anemia is only about 0-1.4%. 1 Thymectomy is hard to perform on patients with severe aplastic anemia（SAA） due to severe pancytopenia.

Breast and dorsal spine relapse of granulocytic sarcoma after allogeneic stem cell transplantation for acute myelomonocytic leukemia:A case report

BACKGROUND Granulocytic sarcoma(GS)is a rare malignant tumor,and relapse is even rarer in the breast and dorsal spine following allogeneic hematopoietic stem cell transplantation.Currently,a standard treatment regimen is not available.CASE SUMMARY A rare case of GS of the right breast and dorsal spine after complete remission of acute myelogenous leukemia is reported here.A 55-year-old female patient presented with a palpable,growing,painless lump as well as worsening dorsal compressive myelopathy.She had a history of acute myelomonocytic leukemia(AML M4)and achieved complete remission after chemotherapy following allogeneic hematopoietic stem cell transplantation.Imaging examinations showed the breast lump and C7-T1 epidural masses suspected of malignancy.Histologic results were compatible with GS in both the right breast and dorsal spine,which were considered extramedullary relapse of the AML treated 4 years earlier.CONCLUSION A rare case of GS relapse following allogeneic hematopoietic stem cell transplantation and guidelines for treatment are discussed.

Midterm outcomes of penetrating keratoplasty following allogeneic cultivated limbal epithelial transplantation in patients with bilateral limbal stem cell deficiency

AIM:To evaluate the midterm outcomes of penetrating keratoplasty(PK)following allogeneic cultivated limbal epithelial transplantation(CLET)for bilateral total limbal stem cell deficiency(LSCD).METHODS:Ten patients(10 eyes)with bilateral LSCD were enrolled in this prospective noncomparative case series study.Each participant underwent PK approximately 6 mo after a CLET.Topical tacrolimus,topical and systemic steroids,and oral ciclosporin were administered postoperatively.Best-corrected visual acuity(BCVA),intraocular pressure(IOP),ocular surface grading scores(OSS),corneal graft epithelial rehabilitation,persistent epithelial defect(PED),immunological rejection,and graft survival rate were assessed.RESULTS:The time interval between PK and allogeneic CLET was 6.90±1.29(6-10)mo.BCVA improved from 2.46±0.32 log MAR preoperatively to 0.77±0.55 log MAR post-PK(P<0.001).Kaplan-Meier analysis of mean graft survival revealed graft survival rates of 100%at 12 and 24 mo and 80.0%at 36 mo.PEDs appeared in 5 eyes at different periods post-PK,and graft rejection occurred in 4 eyes.The total OSS decreased from 12.4±4.4 before allogeneic CLET to 1.4±1.51 after PK.CONCLUSION:A sequential therapy design of PK following allogeneic CLET can maintain a stable ocular surface with improved BCVA despite the relatively high graft rejection rate.