异基因造血干细胞移植治疗高危恶性血液病

目的 分析HLA配型相合同胞供者异基因造血干细胞移植（allo-HSCT）治疗高危恶性血液病的疗效及影响疗效的相关因素。方法 回顾性分析90例有高危因素的恶性血液病患者,其中急性髓细胞白血病（AML）43例,急性淋巴细胞性白血病（ALL）28例,急性混合细胞性白血病（AHL）2例;移植前处于第1次完全缓解期（CR1）11例,均为Ph染色体阳性,第二次及以上CR期23例,未缓解／复发39例;骨髓增生异常综合征（MDS）-难治性贫血伴原始细胞增多或难治性贫血伴原始细胞增多一转化型17例。预处理方案采用全身照射加环磷酰胺（CY／TBI）方案11例,白消安加环磷酰胺方案79例。干细胞来源包括骨髓移植（BMT）27例,外周血造血干细胞移植（PBSCT）30例,BMT＋PBSCT33例;移植物抗宿主病（GVHD）预防采用经典环孢素A加短程甲氨蝶呤（MTX）。平均随访时间为15个月。结果 至随访终点,62．2％（56／90）存活,55．5％（50／90）无病存活,31．1％（28／90）复发。HSCT后预计4年累积总体生存率（OS）为45．5％,无病生存率（DFS）为34．9％。移植前处于CR、未缓解／复发和MDS患者HSCT后4年的累积0s分别为54．0％、28．2％和70．1％（P=0．027）。发生0～Ⅰ和Ⅱ～Ⅳ度GVHD的患者HSCT后的4年OS分别为57．6％和26．7％（P=0．015）,而患者性别、年龄、移植前有无脑膜白血病、预处理方案、干细胞来源均不是OS,DFS及复发的影响因素。多因素分析表明,移植前处于CR期者长期生存率明显提高,而ALL长期生存率明显低于AML／MDS。结论 对有高危因素的血液系统恶性肿瘤患者,选择allo—HSCT可使部分患者延长无病生存乃至根治。移植前处于CR期者长期生存率明显提高,ALL复发率明显高于AML／MDS。对于急性白血病挽救性治疗争取在取得CR后移植;对于MDS患者一经诊断,无需化疗,可尽早移植。     

Comparisons between allogeneic peripheral blood stem cell transplantation and allogeneic bone marrow transplantation in adult hematologic disease: a single center experience

This retrospective study compared the outcomes in 32 adult patients with hematologic diseases (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, severe aplastic anemia) who received allogeneic bone marrow transplantation (BMT, n = 14; median age, 28 years) or allogeneic peripheral blood stem cell transplantation (PBSCT, n = 18; median age, 29 years) from human leukocyte antigen-identical sibling donors. Median follow-up was 58 months in BMT recipients and 18 months in PBSCT recipients. Neutrophil (median, Day 8 vs Day 13, p < 0.001) and platelet engraftment (median, Day 9 vs Day 17, p < 0.001) was faster in the PBSCT group than in the BMT group. Patients receiving PBSCT required less platelet transfusion than those receiving BMT (median, 54 units vs 144 units, p < 0.001), but there was no significant difference in red cell transfusion. At 100 days, there was no difference in the incidence of acute graft-versus-host disease (GVHD) (42.9% vs 33.3%, p = 0.72) or grade II-IV acute GVHD (14.3% vs 5.6%, p = 0.57), and there was no difference in the cumulative incidence of chronic GVHD (20% vs 33.3%, p = 0.67). No chronic GVHD was noted in any relapsed patients (BMT, 5; PBSCT, 3), and no patients with chronic GVHD during follow-up had a relapse. Relapse was the most frequent cause of death inboth groups (BMT, 5/9, 55.6%; PBSCT, 3/4, 75%; p = 0.25); all relapses occurred within 1 year after transplantation. Overall survival was significantly better in the PBSCT group (35.7% vs 77.8%, p = 0.029), but this difference was lost if only hematologic malignancies were analyzed (30.8% vs 63.6%, p = 0.20). Our results are similar to those reported previously, with faster neutrophil and platelet engraftment and less severe acute GVHD and extensive chronic GVHD with PBSCT. Allogeneic PBSCT is a feasible and beneficial alternative to allogeneic BMT in adult hematologic disease.     

Successful treatment with reduced-intensity stem cell transplantation in a case of relapsed refractory central nervous system lymphoma

A 33-year-old male with refractory relapsed central nervous system lymphoma underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA-identical sibling after reduced-intensity conditioning chemotherapy. The preparative regimen for allo-HSCT consisted of fludarabine and busulfan. Cyclosporine (CsA) and short-term methotrexate were used as prophylaxis for acute graft-versus-host disease (GVHD). Although CsA was quickly reduced to induce a graft-versus-lymphoma (GVL) effect, no symptoms of GVHD and GVL effect were evident. Donor lymphocyte infusion (DLI) was performed on day +40 following transplantation. The patient developed acute GVHD (grade III) after DLI, and lymphoma regression was observed after the occurrence of GVHD. Four months after transplantation, complete remission was achieved with extensive chronic GVHD, and the patient continues to be disease free at 15 months after transplantation.     

Second allogeneic peripheral blood stem cell transplantation with fludarabine-based low-intensity conditioning regimen for relapsed myelodysplastic syndrome after allogeneic bone marrow transplantation

We describe the case of a 51-year-old patient with relapsed myelodysplastic syndrome after allogeneic bone marrow transplantation (BMT), who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) after conditioning with a novel regimen consisting of fludarabine, busulfan, and antithymocyte globulin. The second PBSCT was performed early, at 3 months after the initial allogeneic BMT, but it was well tolerated and complete hematologic remission was documented. The patient did not experience any early transplantation-related organ toxicity but died from opportunistic infection 6 months after the second transplantation. Our experience suggests that this novel regimen may induce remission and could be offered to patients relapsing after the first transplantation; however, the fludarabine-containing regimen might be accompanied by profound immunosuppression.     

Bortezomib plus dexamethasone treatment followed by reduced-intensity allogeneic stem cell transplantation for multiple myeloma refractory to high-dose chemotherapy with autologous transplantation

We present two long-term survivors after allogeneic transplantation with reduced-intensity conditioning regimen following relapse after autologous stem cell transplantation (ASCT) for multiple myeloma (MM). The first case was a 47-year-old male with IgG MM treated with 2 courses of high-dose melphalan along with ASCT and thalidomide, resulting in a minimal response. He then received 2 courses of bortezomib plus dexamethasone (BD) regimen, which was discontinued due to peripheral neuropathy. Allogeneic peripheral stem cell transplantation (PBSCT) from a sibling donor was performed after pretreatment with fludarabin (125 mg/m(2)) and melphalan (100 mg/m(2)). Engraftment was observed on day 11 and monoclonal IgG had disappeared 5 months after transplantation. The patient has been in complete remission for more than two and a half years with moderate chronic graft-versus-host disease (GVHD). The second case was a 51-year-old male who relapsed after ASCT for IgA MM. After 3 courses of BD treatment, irradiation to lumbar plasmacytoma, and thalidomide therapy, he received allogeneic PBSCT from a related donor after the same reduced intensity conditioning as performed in case 1. A complete response was observed 6 months after PBSCT. The patient has remained relapse-free for two years without GVHD. BD treatment followed by allogeneic stem cell transplantation with reduced intensity conditioning is supposed to be one of the most powerful strategies for patients showing relapse after ASCT.     

Successful clearance of hepatitis B virus after allogeneic stem cell transplantation: beneficial combination of adoptive immunity transfer and lamivudine

We report a 38-yr-old male with acute lymphocytic leukemia (ALL), whose serological tests for the hepatitis B virus (HBV) before transplantation showed a chronic carrier status, and a liver biopsy specimen revealed chronic liver injury because of HBV. The patient underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his sibling who was hepatitis B surface antibody (HBsAb) positive. He had received lamivudine treatment for the prophylaxis of HBV reactivation during cytotoxic chemotherapy, and lamivudine administration continued after transplantation. Successful engraftment was documented 3 wk after PBSCT, and clearance of the hepatitis B surface antigen (HBsAg) was observed 2 months after PBSCT. Liver function tests transiently showed a mild elevation of aminotransferases on day 25, although this returned to normal after the dose escalation of the immunosuppressive agent. We presume that the combination of adoptive immunity transfer by bone marrow transplantation (BMT) from an HBsAb-positive donor and antiviral drugs such as lamivudine is beneficial in clearing HBV in chronic carriers.     

Successful reduced-intensity stem cell transplantation from an HLA haploidentical 3-loci-mismatched donor on the basis of fetomaternal microchimerism in a patient with advanced acute myeloid Leukemia

A 31-year-old woman with advanced acute myeloid leukemia underwent non-T-cell-depleted (TCD) peripheral blood stem cell transplantation (PBSCT) with a reduced-intensity conditioning regimen. The donor was an HLA haploidentical 3-loci-mismatched complementary sibling who had not inherited maternal HLA antigens. Long-term fetomaternal microchimerism was detected by nested polymerase chain reaction with specific primer typing. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus with minidose methotrexate. Durable engraftment was achieved without severe acute GVHD, and complete remission was obtained. Thus non-TCD HLA haploidentical reduced-intensity PBSCT based on fetomaternal immunological tolerance appears to be feasible. Our results have important implications in the selection of alternative donors and conditioning regimens for allogeneic hematopoietic stem cell transplantation.     

Successful immunotherapy in early relapse of acute myeloid leukemia after nonmyeloablative allogeneic stem cell transplantation

We report on a 35-year-old woman who underwent allogeneic stem cell transplantation (SCT) in second complete remission (CR) of acute myeloid leukemia (AML) after reduced-intensity conditioning with fludarabine and 2 Gy of total body irradiation. For graft-versus-host disease (GVHD) prophylaxis, cyclosporin A (CsA) and mycophenolate mofetil (MMF) were given. On day 27 after SCT complete hematological remission and donor chimerism was documented. However, in CD34(+) bone marrow cells 28% of recipient hematopoiesis persisted. On day +59 leukemic relapse occurred. After discontinuation of CsA and onset of GVHD, complete donor chimerism and hematological CR were achieved which has been maintained for 14 months.     

The analysis of leukemic relapse after allogeneic bone marrow transplantation]

This report presents the analysis of leukemic relapse of 52 patients who received allogeneic bone marrow transplantation between July 1984 and May 1990. Conditioning regimen consisted of TBI + CY and GVHD prophylaxis consisted of cyclosporin-A and methotrexate. The relapse ratios of chronic myelogenous leukemia (CML) (21 in chronic phase, 1 in accelerated phase, 1 in blastic crisis), acute nonlymphocytic leukemia (ANLL) (all 17 in 1st CR), acute lymphocytic leukemia (ALL) (all 12 in 1st CR) were 13%, 18%, 25%, respectively, and 3 year disease free survival (DFS) was as follows, CML 68%, ANLL 72%, ALL 49%. Regarding acute GVHD grading and chronic GVHD presence, 3 year DFS was as follows, acute GVHD 0 degree: 59%, I degree: 78%, II degree-IV degree: 53%, chronic GVHD (+): 82% GVHD (-): 77%. In our center leukemic relapse has been the major cause of death after BMT since 1984. Among 9 relapsed cases, one recurred more than 3 years after BMT, and another one got recurrent leukemia of donor origin.     

Treatment of relapsing leukemia after allogeneic blood stem cell transplantation by using dose-reduced conditioning followed by donor blood stem cells and GM-CSF

Ten patients with high-risk acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS) relapsing early (< 1 year, n = 8) or late (> or = 1 year, n = 2) after allogeneic transplantation were treated with cytoreductive chemotherapy followed by unmanipulated peripheral blood stem cell transplantation (PBSCT) from related (n = 3) and unrelated donors (n = 7). In order to enhance the graft-versus-leukemia effect, patients received no graft-versus-host disease (GVHD) prophylaxis and granulocyte-macrophage colony-stimulating factor (GM-CSF) was given at a dose of 60 micrograms/m2 after transplant. Acute GVHD grade I-IV was seen in all patients. Eight out of ten patients achieved complete remission: one out of two patients with AML and late relapse is in good condition with limited chronic GVHD more than 1 year after the second PBSCT. The other patient died on day +171 after the second PBSCT from cerebral aspergillosis. One patient with blastic phase CML achieved molecular remission but died +330 days after the second PBSCT because of intracranial bleeding. Of the remaining five patients, three died of infectious complications on days +36, +70, and +27, one patient died with extramedullary relapse on day +35, and one from multi-organ failure in association with acute GVHD on day +32 after the second PBSCT. Two out of ten showed progressive disease and died on days +30 and +90, respectively. Although several patients achieved complete remission, the high risk of GVHD and treatment-related mortality should be kept in mind, especially when a second transplant is considered during a period of less than 12 months after the first procedure. Monitoring of minimal residual disease might predict relapse thus preventing high doses of cytotoxic drugs for reconditioning. The potential of GM-CSF to enhance the graft-versus-leukemia reactivity after cytoreductive therapy for allogeneic transplantation warrants further investigation.     

Treatment of pure red cell aplasia after major ABO-incompatible peripheral blood stem cell transplantation by induction of chronic graft-versus-host disease

This report concerns a case of long-lasting pure red cell aplasia (PRCA) with a duration of 178 days after major ABO-incompatible allogeneic peripheral blood stem cell transplantation (PBSCT). The patient needed red blood cell transfusion every week from day 54 following PBSCT. He showed no evidence of GVHD and the dose of cyclosporin A (CsA) was reduced rapidly from day 123, followed by the development of chronic GVHD around day 145. The patient no longer needed transfusions from day 167, the reticulocyte count began to increase on day 179, and antidonor isohemagglutinin titers became undetectable. Chronic GVHD induced by tapering of CsA thus appeared to be related to improvement in PRCA.     

Improved disease-free-survival after transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical unrelated donors in patients with first chronic phase chronic myeloid leukemia

Outcomes after peripheral blood stem cell transplantation (PBSCT) for chronic phase chronic myeloid leukemia (n = 37) were compared with outcomes after bone marrow transplantation (BMT) (n = 54) in the HLA-compatible unrelated donor setting. Median follow-up was 17 months after PBSCT and 29 months after BMT. Both neutrophil and platelet recovery were faster after PBSCT (P <.05). PBSCT was associated with improved immune reconstitution, with higher peripheral blood naive (CD4(+)CD45RA(+)) and memory (CD4(+) CD45RO(+)) helper T cells at 3 months and 12 months after transplantation (P <.03). The cumulative incidence of acute (grades II-IV) and chronic graft-versus-host disease (GVHD) were similar, but BMT was associated with a higher cumulative incidence of severe, acute (grade III-IV) GVHD at 24% as compared with 8% with PBSCT (P <.05). Molecular relapse, defined by 2 consecutive positive polymerase chain reaction assays for bcr-abl within a 4-week interval, occurred in 12 of 45 evaluable patients (27%) after BMT and in 4 of 37 (11%) after PBSCT (not significant). Cytogenetic relapse occurred in 5 of 54 patients after BMT (9%) and in 1 of the 37 (3%) patients after PBSCT (not significant). Seventeen of the 54 patients died after BMT (31%), as compared with 2 of 37 patients after PBSCT (5%). Deaths in the BMT group were associated mainly with infections and severe, acute GVHD. The estimated probability of transplant-related mortality (TRM) and disease-free survival at 1000 days after receiving the transplant were 30% and 64% in the BMT group and 5% and 91% in the PBSCT group (P <.03). Overall survival 1000 days after receiving the transplant was 66% after BMT and 94% after PBSCT (P <.02). In the multivariate analysis, only acute GVHD significantly influenced TRM (P <.01).     

Granulocyte colony-stimulating factor-mobilized allogeneic stem cell transplantation maintains graft-versus-leukemia effects through a perforin-dependent pathway while preventing graft-versus-host disease.

Minimization of graft-versus-host disease (GVHD) with preservation of the graft-versus-leukemia (GVL) effect is a crucial step to improve the overall survival of allogeneic bone marrow transplantation (BMT) for patients with hematological malignancies. We and other investigators have shown that granulocyte colony-stimulating factor (G-CSF)-mobilized allogeneic peripheral stem cell transplantation (PBSCT) reduces the severity of acute GVHD in murine models. In this study, we investigated whether G-CSF-mobilized PBSC maintain their GVL effect in a murine allogeneic transplant model (B6 --> B6D2F1). B6 mice (H-2(b)) were injected subcutaneously with human G-CSF (100 micrograms/kg/d) for 6 days and their splenocytes were harvested on day 7 as a source of PBSC. G-CSF mobilization dramatically improved transplant survival compared with nonmobilized controls (95% v 0%, P <.001). Systemic levels of lipopolysaccharide and tumor necrosis factor-alpha were markedly reduced in recipients of allogeneic G-CSF-mobilized donors, but cytolytic T lymphocyte (CTL) activity against host tumor target cells p815 was retained in those recipients. When leukemia was induced in recipients by coinjection of p815 tumor cells (H-2(d)) at the time of transplantation, all surviving recipients of G-CSF-mobilized B6 donors were leukemia-free at day 70 after transplant, whereas all mice who received T-cell-depleted (TCD) splenocytes from G-CSF-mobilized B6 donors died of leukemia. When splenocytes from G-CSF-mobilized perforin-deficient (pfp-/-) mice were used for transplantation, 90% of recipients died of leukemia, demonstrating that perforin is a crucial pathway mediating GVL effects after G-CSF-mobilized PBSCT. These data illustrate that G-CSF-mobilized allogeneic PBSCT separate GVL from GVHD by preserving perforin-dependent donor CTL activity while reducing systemic inflammation.     

异基因外周血造血干细胞移植治疗急性单核细胞白血病的临床观察

目的评价异基因外周血造血干细胞移植（allo-PBSCT）治疗急性单核细胞白血病（M5）的疗效,并探讨其并发症的预防及处理。方法 16例M5患者接受allo-PBSCT,其中亲缘11例,非亲缘5例。预处理方案：9例采用清髓方案BUCY,7例采用非清髓方案FBC。亲缘的11例均采用环孢素＋短程甲氨蝶呤预防移植物抗宿主病（GVHD）,非亲缘的5例均采用环孢素＋甲氨蝶呤＋吗替麦考酚酯＋ATG。输注的外周血干细胞有核细胞中位数为6.58×108/kg,CD34＋细胞中位数为4.46×106/kg。结果 16例患者中15例均证实植活,余1例在移植早期因HVOD死亡。植入病人中白细胞植入中位时间为13（9~17）d,血小板〉20×109/L的中位时间为16（8~26）d。发生急性GVHD 6例（Ⅰ度4例,Ⅱ度2例）,发生局限性慢性GVHD 7例。目前无病存活10例,中位生存期为45（3~78）个月。结论 Allo-PBSCT是治疗M5的有效手段,并发症少,能有效延长患者生存时间。     

Successful second allogeneic peripheral blood stem cell transplantation and donor lymphocyte infusion in patients with relapsed acute leukemia using the same donors as for the initial allogeneic bone marrow transplantation

We report the successful treatment of two acute lympho- blastic leukemia (ALL) patients who relapsed following allogeneic bone marrow transplantation (allo-BMT) with allogeneic peripheral blood sem cell transplantation(allo-PBSCT) and donor lymphocyte infusion (DLI) from the same HLA-identical related donors as those used for the first allo-BMT. The patients relapsed on days 154 and 351 from the initial allo-BMT, respectively. Since conventional reinduction chemotherapy failed, allo-PBSCT was undertaken while the patients were still myelosuppressed immediately after reinduction chemotherapy. To induce and/or enhance GVL effects following allo-PBSCT, we performed rapid tapering of CsA and added DLI. After allo-PBSCT and DLI, the patients maintained their complete remission at 55 and 48 months post allo-PBSCT, respectively. From these findings, allo-PBSCT and DLI may be a useful treatment strategy for acute leukemia relapsing after allo-BMT.     

Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older

Older recipient and donor age were associated with higher incidences of severe graft‐versus‐host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n = 319), MSD peripheral blood stem cell transplantation (PBSCT) (n = 462), or unrelated CBT (n = 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38–74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P = 0.001) or PBSCT (HR, 2.38; P < 0.001), and transplant‐related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P = 0.002) compared with CBT, the rates of a composite endpoint of GVHD‐free, relapse‐free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT. Am. J. Hematol. 91:E284–E292, 2016. © 2016 Wiley Periodicals, Inc.     

High-dose acyclovir and pre-emptive ganciclovir in prevention of cytomegalovirus disease in pediatric patients following peripheral blood stem cell transplantation

Cytomegalovirus (CMV) disease remains an important cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). We evaluated high-dose acyclovir (HDACV) and pre-emptive ganciclovir to prevent CMV disease in 76 children who underwent peripheral blood stem cell transplantation (PBSCT) and were at risk for CMV reactivation and disease (both recipient and donor seropositive) from May 1998 to April 2003. All received HDACV from day -9 to 6 months post transplant in conjunction with weekly CMV pp65 antigenemia monitoring. The incidence of antigenemia in this cohort was 19.7%, at a median of 22 days post-PBSCT. The frequencies were 26.4 and 4.4% in allogeneic and autologous groups, respectively (P=0.03). Patients with nonmalignant disease had higher CMV antigenemia than those with malignant disease (30.8 vs 8.1%, P=0.02). Age at PBSCT, sex, graft-versus-host disease (GVHD) prophylaxis regimen and presence of acute GVHD did not affect the risk of CMV antigenemia. None of the patients who had positive pp65 antigenemia developed CMV disease during the study period. We conclude that pp65 antigenemia-guided HDACV and pre-emptive ganciclovir may prevent CMV disease in children undergoing PBSCT.     

Successful treatment of myeloid/natural killer cell precursor acute leukemia with allogeneic peripheral blood stem cell transplantation

We report a case of myeloid/NK cell precursor acute leukemia, which was successfully treated with allogeneic peripheral blood stem cell transplantation (allo PBSCT). A 31-year-old woman was admitted to our hospital with general fatigue, anorexia and leukocytosis. Bone marrow aspiration showed infiltration of many atypical blasts. She was diagnosed as having myeloid/NK cell precursor acute leukemia by morphological and immunohistochemical analysis. Complete remission was achieved by induction chemotherapy, but as myeloid/NK cell precursor acute leukemia is reported to have an extremely poor prognosis due to frequent relapse, the patient underwent allo PBSCT from her HLA-identical father, together with a myeloablative conditioning regimen. She suffered several transplantation-related complications including acute graft versus host disease (grade II) and ischemic enterocolitis associated with thrombotic microangiopathy, but these were overcome by supportive therapy. She was discharged on day 168 after allo PBSCT, and so far there has been no evidence of relapse during a follow-up period of 15 months.     

Living-Donor Lobar Lung Transplantation for Broncho-Bronchiolitis Obliterans after Allogeneic Hematopoietic Stem Cell Transplantation: Does Bronchiolitis Obliterans Recur in Transplanted Lungs?

We report a successful case of living-donor lobar lung transplantation (LDLLT) for therapy-resistant broncho-bronchiolitis obliterans (BBO) after allogeneic hematopoietic stem cell transplantation (HSCT). Bronchiolitis obliterans (BO) is one of the late-onset noninfectious pulmonary complications that occur after allogeneic HSCT and is usually resistant to immunosuppressive therapy. A 17-year-old girl with acute lymphoblastic leukemia (ALL) had undergone allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling in 1997. Five years later, she relapsed with ALL and was treated with chemotherapy following stem cell rescue and donor lymphocyte infusion from the original BMT donor. Eight months later, BBO resistant to immunosuppressive therapies, including rituximab, developed in combination with chronic graft-versus-host disease (GVHD). In February 2004, the patient underwent LDLLT from 2 other family members who were mismatched at 3 HLA loci. The patient has been in good health for more than 30 months following LDLLT and shows no sign of BBO in the transplanted lungs, just as with other patients who have undergone lung transplantation for BO associated with chronic GVHD. LDLLT may therefore be considered a viable therapeutic option for the treatment of BO after allogeneic HSCT.