Primary Myelofibrosis Terminated in Basophilic Leukemia and Successful Allogeneic Bone Marrow Transplantation

Transformation of primary myelofibrosis (PMF) to basophilic leukemia is very rare. We report the case of a 44-year-old man who had had PMF for 6 years. His hematopoiesis deteriorated with marked splenomegaly, requiring multiple red blood cell and platelet transfusions. Soon after splenectomy, progressive basophilia (32.3 x 10(9)/L) developed, infiltrating the skin as well as the bone marrow. The patient underwent allogeneic bone marrow transplantation with cells from an HLA-matched sibling. Despite the presence of hyperhistaminemia (99.1 ng/mL) after conditioning with cyclophosphamide, the pregrafting and post-grafting periods were uneventful. Prophylactic administration of both H1 and H2 receptor antagonists and sufficient hydration appeared to be important.     

用BUCY2方案预处理的异基因骨髓移植治疗急性白血病

利用ＢＵＣＹ２方案作预处理对２例急性因病患者实施同种异基因骨髓移植，输入的供体骨髓分别于术后第１８天和１７天植活；ＢＵＣＹ２预处理的毒性较小，化疗反应较易耐受；２例患者均于术后第１８天出现急性移植物抗宿主病（ＧＶＨＤ，Ⅱ级），现已持久植活达２年和１年半，术后５个月复查时，患者的造血系统仍为供体来源。     

Transplantation of HL-A Identical Allogeneic Bone Marrow to a Patient With Acute Lymphocytic Leukemia

An 8-year-old boy with acute lymphocytic leukemia, no longer responsive toconventional chemotherapy after 2 years,was successfully grafted with bone marrow from his HL-A genotypically identical 10-year-old sister. Prior to transplantation, he had received 141 bloodcomponent transfusions and had becomesensitized to histocompatibility antigens(HL-A), as demonstrated by the presenceof circulating lymphocytotoxic antibodies.Except for the occurrence of a possiblemild graft-versus-host-reaction and a documented cytomegalovirus infection, thepatient remained clinically well until fullreturn of his leukemia 91 days after thetransplant. This case demonstrates thatbone marrow transplantation can be accomplished between HL-A identical siblings even though the recipient may havebeen previously sensitized to other HL-Aantigens by earlier transfusion. Allogenicbone marrow transplantation offers theopportunity for remissions in patientswith leukemia unresponsive to conventional drug therapy.

Submitted on May 25, 1970 Revised on July 15, 1970 Accepted on July 16, 1970     

Successful Treatment with Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation in a Patient with Acute Myeloid Leukemia Complicated with Pulmonary Infection

We describe the case of a 48-year-old man with acute myeloid leukemia complicated with pulmonary infection that was successfully treated by nonmyeloablative allogeneic peripheral blood stem cell transplantation with conditioning by low-dose total body irradiation and fludarabine. The disease was diagnosed immunophenotypically as myeloid/natural killer cell precursor acute leukemia. After two courses of induction therapy, complete remission was achieved. However, the patient developed pneumonia from prolonged severe neutropenia. Nonmyeloablative allogeneic transplantation was performed because of the active pulmonary infection and the patient's poor performance status. Myelosuppression after transplantation was mild, and the pulmonary infiltration was well controlled during the course of treatment. At the time of this report the patient was an outpatient in our clinic, and on day 500, his disease was in remission with well-controlled chronic graft-versus-host disease. Nonmyeloablative transplantation may provide a new therapeutic strategy for treating patients with active infection who cannot tolerate conventional transplantation with high-dose chemoradiotherapy.     

Successful Cytoreduction with CAG (cytarabine,Aclarubicin and G-CSF) Therapy in Refractory Acute Myelogenous Leukemia before Allogeneic Stem Cell Transplantation

Refractory acute myelogenous leukemia (AML) has a poor prognosis, and a long-term survival cannot be expected in most patients even if allogeneic bone marrow transplantation (allo-BMT) or allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is performed. An abundance of residual leukemic cells and poor performance status of patients before allo-BMT are often associated with a high relapse rate and high transplant-related mortality. Thus, to improve the prognosis of patients with refractory AML undergoing allo-BMT, it is necessary to reduce the leukemic cell volume as low as possible without severe complications. In this report, we used CAG (cytarabine, aclarubicin and granulocyte colony-stimulating factor (G-CSF)) therapy for cytoreduction before allo-BMT or allo-PBSCT in five patients with refractory AML. One of them achieved complete remission (CR) by CAG therapy alone and others achieved major tumor reduction prior to BMT and PBSCT. All patients achieved CR after allo-BMT and allo-PBSCT without severe complications. Three of them have remained CR for 9, 21 and 30 months, respectively. Although the results of this feasibility study are preliminary, the pre-transplant CAG therapy for refractory AML deserves further evaluation.     

Bone Marrow Transplantation with a Reduced-Intensity Conditioning Regimen in a Patient with Wegener Granulomatosis and Therapy-Related Leukemia

We describe a patient with Wegener granulomatosis (WG) who underwent long-term cyclophosphamide treatment and thereafter developed acute myelogenous leukemia (AML). After the AML was induced into remission, the patient received an allogeneic stem cell transplant (allo-SCT) from his sibling after undergoing a reduced-intensity conditioning regimen. His clinical course shortly after allo-SCT was uneventful. No clinically apparent acute or chronic graft-versus-host disease developed. Repeated analysis of the peripheral blood lymphocytes after transplantation showed complete donor chimerism. The level of proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) remained undetectable until 4 months after transplantation, when it began to increase. When the level of PR3-ANCA peaked, the patient suddenly presented with fever and joint pain, which later spontaneously resolved in parallel with the declining titer of PR3-ANCA. He is now in remission for both AML and WG at 22 months after transplantation. The patient's clinical course after allo-SCT may provide us with valuable information regarding the establishment of allo-SCT as a therapeutic option for WG.     

Graft-versus-host Disease Confined Solely to Intestine after Allogeneic Peripheral Blood Stem Cells Transplantation in a Patient with Chronic Myelogenous Leukemia

We describe a patient with chronic myelogenous leukemia who developing severe intestinal bleeding after allogeneic peripheral blood stem cells transplantation (allo-PBSCT). PBSC were obtained from an HLA one-locus mismatch sibling donor. On day 26 after PBSCT, although there was no sign of graft-versus-host disease (GVHD) in either the skin or the liver, diarrhea and severe intestinal bleeding occurred. The histopathological examination of the colon revealed complete denudation of the epithelial cells of the mucosa and no obvious apoptosis. Neither red cell fragments nor hemorrhagic diathesis was seen during this episode and the patient was diagnosed as having GVHD. Methylpredonisolone followed by FK506 may be effective in controlling intestinal bleeding and was used in our patient. Acute GVHD involving only the intestine has rarely been described but when using HLA-mismatched PBSCs, acute GVHD may occur severely and atypically.     

Risk-Adapted Preemptive Therapy for Cytomegalovirus Disease after Allogeneic Stem Cell Transplantation: A Single-Center Experience in Korea

Cytomegalovirus (CMV) remains a major cause of infection in recipients of hematopoietic stem cell transplants (HSCT) and results in significant mortality and morbidity. We present the results of CMV pp65 antigenemia-guided, risk-adapted preemptive therapy aimed at preventing CMV disease in allogeneic HSCT. Preemptive ganciclovir treatment was started when more than 5 CMV antigen-positive cells were detected in the low-risk group (with grade 0-I acute GVHD and matched related HSCT) and when any antigen-positive cells were seen in the high-risk group (with grade II-IV acute GVHD or matched unrelated HSCT). At least 1 episode of antigenemia was observed in 53 (59.6%) of 89 patients before day 100, and preemptive therapy was performed in 33 patients. CMV disease occurred in 6 patients (5 in the high-risk group and 1 in the low-risk group), and late CMV disease developed in 4 patients. Only 1 patient died of CMV pneumonitis before day 100. Neutropenia was observed in 51.5% of ganciclovir-treated patients, and coinfection/superinfection was observed in 42.4%. A strategy of ganciclovir treatment focusing on patients at higher risk could reduce the toxicity from the antiviral drug and be cost-effective. Extended surveillance for CMV disease using more sensitive diagnostic methods is necessary in high-risk patients.     

慢性髓细胞性白血病骨髓移植后细胞遗传学动态观察

本文报道12例慢性髓性白血病(CML)患者骨髓移植(BMT)后染色体系统的追踪概况。BMT后三种核型:1.完全供者细胞;2.正常供者/受者或供者/受者Ph(+);3.正常供者/受者/受者Ph(+)细胞。BMT后1例病人复发,染色体伴有附加异常+(18,21)、t(4;15)、b13q、15q~+、8q~+。附加异常为研究移植后细胞遗传学能否帮助新型染色体核型及与复发的关系有重要意义。     

Recurrent Acute Myositis after Allogeneic Bone Marrow Transplantation for Myelodysplasia

A 54-year-old woman developed polymyositis 6 months after allogeneic bone marrow transplantation (BMT) for acute myelogenous leukemia transformed from myelodysplasia. At the onset of myositis, the patient had oral dryness, and the histology of oral mucosa was compatible with chronic graft-versus-host disease (GVHD). Muscle biopsy revealed focal muscle necrosis with massive lymphocytic infiltration. She was diagnosed with polymyositis, and the dose of cyclosporine was increased. Three months later, a complete resolution of myositis had been obtained, and the cyclosporine was tapered off. However, 51 months after the first episode of myositis, she again noted severe myalgia and was diagnosed with a recurrence of polymyositis based on high serum creatinine kinase (CK) and the findings of magnetic resonance imaging (MRI). At that time, chronic GVHD in other organs was not present. She achieved a second remission of polymyositis with cyclosporine, and has remained in remission for 4 years. The pathogenesis of myositis can be attributed to the immunologic imbalance characteristic of the post-allogeneic BMT setting.     

Glanzmann Thrombasthenia with Acute Myeloid Leukemia Successfully Treated by Bone Marrow Transplantation

We report successful treatment by bone marrow transplantation (BMT) in an acute myeloid leukemia (AML) patient with Glanzmann thrombasthenia (GT). Genetic analysis revealed that a novel point mutation in exon 3 of the GPIIb gene led to abnormal splicing resulting in an amino acid substitution and an in-frame deletion of 3 amino acid residues. Expression studies suggested a rapid degradation of the uncomplexed protein within the cells. Induction therapy for AML was performed with frequent platelet transfusions because of the patient's severe hemorrhagic manifestations. In the second remission, the patient was successfully treated by BMT from an HLA-matched unrelated donor. Platelet function returned to normal, and the GT phenotype completely disappeared. Our experience suggests that BMT is a curative therapeutic strategy for GT. Furthermore, we believe this study is the first to demonstrate that engraftment after BMT for AML can be determined by monitoring the congenital genetic defect of GT.     

血浆置换术治疗异基因骨髓移植后纯红细胞再生障碍性贫血（附1例报告）

本文报告１例重症再生障碍性贫血患者因接受ＡＢＯ血型不合供体的异基因骨髓移植后并发纯红细胞再生障碍性贫血。采用血浆置换术２次,共置换出患者体内血浆３．２Ｌ后,血清抗＂Ａ＂血型抗体滴度由１∶６４下降至１∶８,骨髓幼红细胞比分逐渐上升,由血浆置换术前的０．００５上升至术后１２周的０．２１;红细胞输注量逐渐减少,血红蛋白逐渐升高,患者目前已完全恢复正常２年余。     

Recurrent Extramedullary Relapse of Acute Promyelocytic Leukemia after Allogeneic Stem Cell Transplantation: Successful Treatment by Arsenic Trioxide in Combination with Local Radiotherapy

Isolated extramedullary relapse is rare in patients with acute promyelocytic leukemia (APL) after allogeneic stem cell transplantation (SCT), and an optimal therapy for it has not been established. We describe a patient with APL who developed serially occurring extramedullary disease (EMD) after SCT. We confirmed that EMD had arisen from the recipient's APL blasts by detecting t(15;17) and PML/RARalpha from the tumor cell suspension. The patient displayed EMD 4 times at different sites. Administration of all-trans retinoic acid with local radiotherapy and with chemotherapy for the first to third EMDs resulted in regression of the tumors. However, these regimens did not prevent the subsequent occurrence of new EMD. For the fourth EMD, intravenous administration of arsenic trioxide followed by local radiotherapy resulted in the disappearance of EMD, and no further EMD has developed to date. In the present case, the bone marrow was in morphologic and molecular remission during the course of recurrent EMD. The accumulation of detailed cases is needed to elucidate the pathogenesis, predisposing factors, and optimal therapy for EMD in APL after SCT.     

Successful Stem Cell Transplantation without Cryopreservation from a Microchimeric Haploidentical Sibling for Refractory Acute Myeloid Leukemia Complicated with Critical Thrombophlebitis and Cellulitis

We describe the case of a 38-year-old male patient who had acute myeloid leukemia and developed prolonged neutropenia after induction chemotherapy. He developed thrombotic complications at multiple sites. Thrombophlebitis of the hemorrhoidal plexus became exacerbated and developed into critical cellulitis. Because the patient had no human leukocyte antigen-identical sibling, we considered an alternative donor. Because of the necessity for early neutrophil recovery to resolve the critical infection, we proceeded with allogeneic peripheral blood stem cell transplantation (PBSCT) from a microchimeric haploidentical sibling donor. We infused peripheral blood mononuclear cells directly into the patient without cryopreservation and thawing procedures. We aimed for the contaminating granulocytes to act as a granulocyte transfusion. Actually, the neutrophils increased to 1.6 x 10(9)/L on day 1, when the patient showed a temporary resolution of infection. Engraftment was achieved shortly after neutropenic nadir, and acute graft-versus-host disease (GVHD) has been well controlled. Although the patient experiences extensive chronic GVHD, he has been well as an outpatient with a 90% Karnofsky performance status score. The leukemia has been in complete remission for more than 1 year. These findings suggest the clinical utility of a salvage therapy with allogeneic PBSCT from a microchimeric haploidentical donor to treat refractory leukemia concurrent with life-threatening infection.     

Successful Reduced-intensity Stem Cell Transplant from One-locus HLA-mismatched Unrelated Cord Blood after Rejection of Unrelated Bone Marrow in an Infant with Myelogenous Leukemia

An 8-month-old girl had acute myelogenous leukemia (EAB M2) that relapsed 5 months after diagnosis during intensive consolidation chemotherapy. She underwent bone marrow transplantation (BMT) from an HLA-A, -B, -C and -DR phenotypically matched, but one locus DRB1 genotypically mismatched unrelated donor, but rejection occurred.

Subsequently, she received reduced-intensity transplant (fludarabine/cytosine arabinoside/cyclophosphamide) from one locus HLA-A-mismatched, but DRB1 genotypically matched unrelated cord blood stem cells and remission was induced by acute GVHD (grade II) that progressed to chronic GVHD with involvement of the skin, liver, and gastrointestinal tract. In this case, it seems that remission was induced by an adequate graft-versus-leukemia effect and mild chronic graft-versus-disease due to the HLA-A difference more than DRB1 matched between the patient and the cord blood stem cells.     

AA患者异基因骨髓移植后合并急性胰腺炎

目的：报告少见病例。方法：治疗1例病史11年的再生障碍性贫血（再障）患者。结果：ABO血型相同、HLA完全相合的异基因骨髓移植（ALLO－BMT）后并发急性胰腺炎，结论：ALLO-BMT并发急性胰腺炎可能与含铁血黄素沉积和（或）GVHD有关，但应排除丙型肝炎所致词素。