Allogeneic Hematopoietic Stem Cell Transplantation: A Salvage Treatment for Relapsed or Refractory Lymphoma

To analyze the efficacy and safety of allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in patients with relapsed or refractory lymphoma, the therapeutic efficacy, safety, and survival of 23 patients were evaluated. There were 18 (78.3 %) patients with relapsed lymphoma and 5 (21.7 %) patients with refractory lymphoma. Patients were grafted from human leukocyte antigen (HLA)-matched (10) or mismatched (7) related donors, or matched unrelated donors (6). The responses after Allo-HSCT included 13 (56.5 %) cases of complete remission, 5 (21.7 %) cases of partial remission, and 5 (21.7 %) cases of progressive disease. Overall, 16 of 23 patients were alive at a median follow up of 1,035 days (range 60–2,613), five patients died because of non-relapsed mortality, and two patients died of progressive disease. Progression-free survival rates were 64.6 and 48.4 % at 12 and 24 months, respectively, and overall survival rates were 68.6 and 59.5 % at 12 and 24 months, respectively. Allo-HSCT may be a salvage treatment for relapsed or refractory lymphoma. Myeloablative conditioning regimens may be effective and safe.     

Splenectomy for Severe Autoimmune Cytopenias after Allogeneic Stem Cell Transplantation: Case Report

Autoimmune cytopenias are rare but serious complications after hematopoietic stem cell transplantation (HSCT). We per-formed splenectomy in 2 patients who had severe autoimmune cytopenias after allogeneic HSCT (allo-HSCT) that were resist-ant to immunosuppressive treatment. The first patient underwent unrelated allo-HSCT for chronic granulocytic leukemia(CGL) in July 2000. Seven months later, red blood cell and platelet counts went down. The results of a direct Coombs test were intermittently positive. The patient was resistant to therapy with steroids and high-dose immunoglobulin. After a splenectomy was performed in February 2001, the hemoglobin concentration and platelet count improved. Her blood counts remained stable, with a hemoglobin level of approximately 110 g/L and a platelet count >100 x 109/L. She continued therapy with itraconazole, valacyclovir, and penicillin. Some months later, the patient was readmitted for fulminant septic infection, which had a fatal outcome. The second patient underwent related allo-SCT for CGL in January 2003. Seven months later, he was readmitted for intraocular bleeding accompanied by severe thrombocytopenia with antiplatelet antibodies. The patient was resistant to steroid and high-dose immunoglobulin therapy. A splenectomy was performed in September 2003. His platelet count normalized and remains stable. The patient continues therapy with itraconazole, valacyclovir, and penicillin and has not experienced any serious infection. We assume that splenectomy is an effective treatment for resistant immune cytopenias after allo-HSCT. However, severe late infections can compromise the outcome.     

异基因造血干细胞移植治疗NK／T细胞淋巴瘤

目的：探讨异基因造血干细胞移植（allo—HSCT）治疗NK／T细胞淋巴瘤的疗效。方法：对1例NK／T细胞淋巴瘤患者进行allo-HSCT,采用改良马利兰（Bu）／环磷酰胺（Bu／Cy）预处理方案进行了亲缘HLA全相合的外周血干细胞移植,移植物抗宿主病（GVHD）的预防采用环孢素A联合短疗程甲氨蝶呤的方案。移植后予鼻窦及颈部淋巴结区局部放疗,早期减停环孢素A和供者淋巴细胞输注防治复发。结果：患者移植后造血恢复顺利,中性粒细胞绝对数（ANC）〉0．5×10 9／L时间为＋13d,血小板〉20×10 9／L时间为＋15d。移植后未发生急性GVHD,发生肝脏及口腔的慢性GVHD,使用小剂量甲氨蝶呤和泼尼松后控制。随访至移植后8月余,造血功能恢复良好,病情处于持续完全缓解状态,仍在继续随访中。结论：allo-HSCT对NK／T细胞淋巴瘤可能是一种有效的根治方法,移植后的局部放疗及供者淋巴细胞输注能预防复发。

Abstract：

Objective： To explore the therapeutic effect of allogeneic hematopoietic stem cell transplantation （allo HSCT） for NK/T cell lymphoma. Methods： One patient with NK/T-cell lymphoma received allo-HSCT. The patient received conditioning regimens of improved busulfan/cyclophosphamide and relative HLA-identical peripheral blood stem cell transplantation. Graft versus host disease （GVHD） prophylaxis consisted of cyclosporin-A （CsA） and short course of methotrerate. The sinus and cervical lymph node area were received local ra diotherapy, and it followed by early cyclosporine tapering and donor lymphocyte infusion to prevent relapse after allo HSCT. Results： The hematopoietic stem cell was transplanted successfully. The ANC and PLT were grafted respectively in ＋ 13d and ＋ 15d. None of the acute GVHD was observed. The chronic GVHD involved liver and oral after transplantation, and it was controlled by low dose of methotrerate and prednisone. The patient was followed up for 8 months after allo-HSCT, and the state of illness retained continuous complete remission. Conclusions： Treatment of allo-HSCT was an effective radical cure for NK/T-cell lymphoma, and local radio therapy and donor lymphocyte infusion were used to prevent relapse post transplant.     

EBV-Positive Burkitt Lymphoma as a Late-Onset Posttransplantion Lymphoproliferative Disorder after Allogeneic Stem Cell Transplantation

Posttransplantation lymphoproliferative disorder (PTLD) is one of the well-recognized complications after allogeneic stem cell transplantation (SCT). It generally occurs early after SCT, and only a few reports of late-onset cases are available. We report a 58-year-old male patient who developed lymphoma 4 years after allogeneic SCT for chronic myeloid leukemia. The presence of c-myc translocation and Epstein-Barr virus-encoded RNA in the lymphoma cells, without rearrangement of the 3'-bcr region, confirmed the histopathologic diagnosis of Burkitt lymphoma. DNA chimerism analysis revealed that the lymphoma cells were of donor origin. The patient achieved complete response with intensive chemotherapy. To our knowledge, this is the first report of Burkitt lymphoma as a PTLD occurring after allogeneic SCT.     

Advances in Allogeneic Stem Cell Transplantation for Hemoglobinopathies

Hematopoietic stem cell transplantation (SCT) is currently the only potential curative therapy for thalassemia and sickle cell disease. A myeloablative conditioning regimen has been in use to eradicate the disease. Nowadays, improved preparative and conditioning methods are used including reduced intensity conditioning regimens. Such developments have allowed transplantation of more advanced hemoglobinopathy diseases. Stem cell transplant sources became more accessible including umbilical cord blood and alternate donor. However, donor human leukocyte antigen (HLA) disparity still carries a significant risk of morbidity and mortality.     

Diverse Clinical Applications Using Advantages of Allogeneic Peripheral Blood Stem Cell Transplantation

The diverse clinical applications of allogeneic peripheral blood stem cells based on use of their advantages are summarized. It is apparent that more stem cells and T-lymphocytes can be harvested by mobilization treatment with cytokines from healthy donors in allogeneic peripheral blood stem cell transplantation (PBSCT) than in bone marrow transplantation. It is also clear that a stronger graft-versus-tumor effect can be induced with allogeneic PBSCT than with bone marrow transplantation. One merit of allogeneic PBSCT is that it allows clinicians to design diverse clinical applications. It would appear that allogeneic PBSCT may be preferable in special clinical settings, such as advanced hematological malignancies, situations requiring a strong graft-versus-tumor effect, nonmyeloablative stem cell transplantation, and situations requiring a megadose of stem cells. Cytokine-primed peripheral blood stem cells can also be used for adoptive immunotherapy, such as a nonprimed donor lymphocyte infusion.     

Allogeneic Peripheral Blood Stem Cell Transplantation for Severe Aplastic Anemia

Abstract: Allogeneic peripheral blood stem cell transplantation (PBSCT) is rarely applied for the treatment of severe aplastic anemia (SAA) because of questionable durability of engraftment and increased risk of graft versus host disease (GVHD). We performed allogeneic PBSCT in 3 SAA patients from their human leukocyte antigen (HLA)–identical siblings. One received bone marrow after conditioning with cyclophoshamide (Cy) plus antithymocyte globulin. He had a second transplant with peripheral blood stem cells from the original donor because of a graft failure (GF). Two other patients received PBSCT as a first option, with Cy as the only conditioning drug. The 3 patients received short‐term methotrexate and cyclosporine as a postgrafting immunosupression. In the latter 2 cases, no GF has been observed, and a successful and complete hematological recovery was achieved and maintained for 28 and 25 months, respectively. In conclusion, PBSCT provides a quick and complete hematological recovery in SAA patients.     

Ocular Manifestation of Acute Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation

A 26-year-old woman with acute myeloid leukemia underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical brother. Eighteen days after transplantation, the patient developed grade II acute graft-versus-host disease (GVHD) and was treated with corticosteroids. On day 38, the patient complained of eye pain and lacrimation. A slitlamp examination revealed corneal ulcers and pseudomembranous formation in both eyes. Histologic and immunohistochemical examinations of the pseudomembrane disclosed an infiltrate dominated by T cells. A cytogenetic study of the pseudomembrane by fluorescence in situ hybridization identified a Y chromosome in the infiltrated mononuclear cells. Surveillance cultures from conjunctival swabs were negative. Thus, we diagnosed these ocular manifestations as an ocular involvement of acute GVHD.     

Human Herpesvirus 6 Meningoencephalitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

We retrospectively investigated the clinical characteristics of human herpesvirus 6 (HHV-6) meningoencephalitis within 100 days after allogeneic hematopoietic stem cell transplantation (HSCT). Of 1148 patients who received transplants between January 1999 and December 2003, 11 patients (0.96%) with HHV-6 meningoencephalitis were identified. Ten of 11 recipients received hematopoietic stem cells from donors other than HLA-identical siblings. Confusion was the most frequent central nervous system (CNS) symptom, and a skin rash with high-grade fever preceded the CNS symptoms in 9 patients. Magnetic resonance imaging of the brain showed an abnormal increased T2 signal in the hypothalamus of 5 patients. Eight patients were treated with ganciclovir, and an improvement of CNS symptoms was obtained in 3 patients; 3 patients treated with acyclovir showed no improvement. Improvement in the meningoencephalitis seemed less frequent in patients with abnormal findings in the hypothalamus than in those without such findings. Because the symptoms of HHV-6 meningoencephalitis mimicked those of cyclosporine- or tacrolimus-induced encephalopathy, the drugs were withdrawn at the onset of CNS symptoms in 10 patients, resulting in the development of grade IV graft-versus-host disease (GVHD) in 5 patients. Three patients died of HHV-6 meningoencephalitis, and 6 died of other causes, including GVHD. In conclusion, HHV-6 meningoencephalitis is a rare but potentially life-threatening complication in patients who undergo allogeneic HSCT. Careful assessment of the clinical findings and the brain may allow early and precise diagnosis of HHV-6 meningoencephalitis and contribute to improving its prognosis.     

Sustained Cytogenetic Remission Induced by Imatinib Mesylate in a Chronic Myeloid Leukemia Patient Who Had a Relapse into Lymphoid Crisis after Allogeneic Hematopoietic Stem Cell Transplantation

We report on the response to imatinib mesylate in a chronic myeloid leukemia patient who, after undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) for treatment of lymphoid blastic crisis, had a relapse into blastic crisis despite the presence of chronic and grade II acute graft-versus-host disease (GVHD). Complete hematologic response and the disappearance of the Bcr-Abl fusion signal on fluorescence in situ hybridization analysis were achieved after 10 weeks of imatinib therapy and were maintained for 26 months with no adverse effects, including recurrence of GVHD. This case highlights the ability of imatinib to induce sustained hematologic and cytogenetic remission in some patients who have had relapses into advanced-stage chronic myeloid leukemia after alloHSCT.     

Comparison of Myeloablative and Nonmyeloablative Hematopoietic Stem Cell Transplantation for Treatment of Chronic Myeloid Leukemia

This retrospective study compared outcomes for 81 chronic myeloid leukemia patients who underwent myeloablative or nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT). Sixty-five patients received myeloablative HSCT, and 16 patients received fludarabine (Fd), low-dose busulfan (Bu), and antithymocyte globulin (ATG) in nonmyeloablative HSCT. We determined overall survival (OS) and disease-free survival (DFS), as well as the occurrence of acute and chronic graft-versus-host disease (GVHD). The incidences of acute GVHD of grades II to IV were 14.0% and 18.7% for the myeloablative and nonmyeloablative groups, respectively. The incidence of chronic GVHD was significantly higher in the nonmyeloablative group (80% versus 66%). Five-year OS and DFS rates were significantly higher in nonmyeloablative group (70% for both), compared with 56% and 54%, respectively, for the myeloablative group. A univariate analysis, however, revealed a strong but statistically insignificant trend for enhanced overall OS and DFS in the nonmyeloablative group (P = .1 and .07, respectively). A multivariate analysis with the factors of treatment, age, sex, acute and chronic GVHD, and disease status at the time of transplantation revealed that both OS and DFS were significantly higher in the nonmyeloablative group than in the myeloablative group. These findings suggest that nonmyeloablative Fd/Bu/ATG treatment is at least not inferior (and quite probably superior) in terms of patient outcome compared with standard myeloablative therapy. Further larger-scale randomized clinical trials are warranted to clarify the efficacy of this treatment regimen.     

ABO血型不合同胞间异基因外周血干细胞移植后纯红细胞再生障碍性贫血3例报告

目的：探讨ABO血型不合异基因外周血干细胞移植后纯红细胞再生障碍性贫血(PRCA)的治疗。方法：报道3例病例并进行文献复习。结果：3例HLA配型完全相合、ABO血型主要不合的患者进行同胞间异基因外周血干细胞移植获得成功,但移植后均出现PRCA。1例经大剂量糖皮质激素联合大剂量免疫球蛋白治疗,2例经大剂量糖皮质激素联合血浆置换治疗后血型均转为供者血型,血红蛋白逐渐恢复正常。结论：大剂量糖皮质激素联合血浆置换或大剂量免疫球蛋白是治疗ABO血型不合异基因外周血干细胞移植后PRCA的有效方法。     

异基因外周血干细胞移植治疗白血病9例临床分析

目的评价异基因外周血干细胞移植（Allo-PBSCT）治疗白血病的疗效及移植相关并发症。方法回顾分析9例白血病患者行同胞供者Allo-PBSCT治疗。预处理方案为改良马利兰加环磷酰胺（Bu／CY）;预防移植物抗宿主病（GVHD）采用环孢素A（CSA）加短程甲氨蝶呤（MTX）和霉酚酸酯（MMF）。结果8例患者均获得造血重建,白细胞植活的中位时间为15（13～16）d;1例未植入。出现GVHD7例,肝静脉闭塞病（HVOD）3例,出血性膀胱炎（HC）1例。中位随访时间为13（0～30）个月6例存活,其中5例为无病存活,3例死亡。结论Allo-PBSCT治疗白血病有效,移植相关并发症可接受。     

Experience with the Use of Salazosulfapyridine for Intractable Diarrhea after Hematopoietic Stem Cell Transplantation

We encountered 2 children with intractable diarrhea after allogeneic hematopoietic stem cell transplantation (SCT). In both cases, salazosulfapyridine (SASP) was administered to treat the diarrhea. One patient was a 14-year-old male with acute myelogenous leukemia who received SCT from a related HLA-identical donor. The leukemia recurred early, and a second SCT from the same donor was performed approximately half a year later. Because intestinal graft-versus-host disease (GVHD) was observed, steroids and octreotide were administered, but the symptoms were not improved. Thereafter, SASP was administered, and the symptoms remitted 9 days later. The other patient was a 12-year-old male with chronic myelogenous leukemia who received SCT from an unrelated HLA-identical donor. Diarrhea and abdominal pain developed early after engraftment and did not respond to either steroids or tacrolimus. Oral administration of SASP was initiated on day 236, and the diarrhea remitted 4 days later without recurrence thereafter. SASP may be effective in children for the digestive system symptoms of chronic GVHD.     

Room for Improvement: A 20-Year Single Center Experience with Allogeneic Stem Cell Transplantation for Myelodysplastic Syndromes

Allogeneic stem cell transplantation (allo-SCT) remains the only curative therapeutic approach for patients with myelodysplastic syndromes (MDS). The aim of the study was to assess the efficacy/safety of allo-SCT as well as to identify factors influencing post-transplant survival. One hundred and two MDS patients (median age: 48 years; 57 males) who underwent allo-SCT were retrospectively evaluated. Twenty seven patients were transplanted from HLA-matched sibling and 75 patients received grafts from unrelated donors. Peripheral blood was a source of stem cell for 79 patients. Reduced intensity conditioning was used in 64 subjects. Acute and chronic graft versus host disease (GvHD) developed in 61 and 19 of patients, respectively. In total, 61 patients have died. The causes of deaths included infectious complications (n = 30), steroid-resistant GvHD (n = 17), MDS relapse (n = 9) and transformation to AML (n = 5). Non-relapse mortality and cumulative incidence of relapse at 2 years were 49.8% and 9%, respectively. 41 patients are alive at last contact and present full donor chimerism. 38 patients remain in complete hematological remission (CHR), 3 patients had CHR with incomplete platelet recovery. Median follow-up from diagnosis of MDS and transplantation are 27.1 months and 7 months respectively. Overall survival and relapse-free survival were 41% at 2 years. Increased serum ferritin level > 1000 ng/ml, presence of acute GvHD, grades III–IV acute GvHD and high hematopoietic cell transplantation-comorbidity index were found to negatively influenced survival. Allo-SCT for MDS is feasible procedure with a proportion of patients to be cured.     

Central Nervous System-related Graft-versus-host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hemopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for refractory hematological malignancies. However, there are many treatment-related complications, including organ disorders, graft-versus-host disease (GVHD), and infectious diseases. Furthermore, there are many unclear points regarding central nervous system (CNS) complications, and the prognosis in patients with CNS complications is extremely poor. We herein report a 49-year-old woman who developed CNS-GVHD after a second transplantation for therapy-related myelodysplastic syndrome. CNS-GVHD in this case was refractory to all treatments, including steroids, and progressed. We also present a review of the literature about the symptoms, diagnosis, and treatment of CNS-GVHD.     

Impact of Cytogenetics on Outcome of Stem Cell Transplantation for Acute Myeloid Leukemia in First Remission: A Large-Scale Retrospective Analysis of Data from the Japan Society for Hematopoietic Cell Transplantation

On the basis of transplantation data from the Japan Society for Hematopoietic Cell Transplantation, we retrospectively analyzed the impact of cytogenetics at diagnosis on the outcome of transplantation in 628 patients with acute myeloid leukemia who underwent autologous (n = 200), allogeneic related (n = 363), or allogenic unrelated (n = 65) stem cell transplantation (SCT) at first complete remission. For autologous SCT, patients at good cytogenetic risk had a significantly lower relapse rate (P = .017) and a significantly higher event-free survival (EFS) (P = .013) compared with those at intermediate risk. For allogeneic SCT, patients at good cytogenetic risk had a significantly lower relapse rate (P = .019) and insignificantly higher EFS (P = .093) than those at poor risk. For unrelated SCT, there was no significant difference in relapse rate or EFS between patients at good risk and those at intermediate risk. Comparison of the 3 transplantation modalities revealed that autologous SCT patients had a significantly higher incidence of relapse compared with related or unrelated SCT patients in the intermediate-risk group but not in the good-risk group. However, there were no significant differences in EFS among the 3 transplant modalities in either of these 2 risk groups. In multivariate analysis, cytogenetics was found to be an independent predictor of relapse as well as of treatment failure. on behalf of the Japan Society for Hematopoietic Cell Transplantation     

Treatment of Aregeneratoric Anemia Following an ABO-Incompatible Allogeneic Peripheral Blood Stem Cell Transplantation: A Case Report

Aregeneratoric anemia (AA) occurs rarely after ABO-incompatible allogeneic peripheral blood stem cell transplantation (alloPBSCT), and its management is generally difficult. Here, we present a 31-year-old white man with myelodysplastic syndrome who developed AA after receiving stem cells from his human leukocyte antigen (HLA) identical, but ABO-incompatible sibling. Because his anti-A antibody titers were high, therapy with conventional doses of erythropoietin and prednisolone failed to treat the AA. Following 8 cycles of plasma exchange and higher doses of erythropoetin and prednisolone as well as danazol administration, anti-A titers decreased, and his anemia improved significantly. In conclusion, to treat and obtain a low titer of antibodies in a patient with AA following an ABO-incompatible alloPBSCT, higher doses of erythopoietin and corticosteroids associated with plasma exchange have to be used.