ABSTRACT
Poor prognostic factors, such as transfusion dependency and chromosomal risk, need to be considered in the indication of allogeneic hematopoietic cell transplantation (allo-HCT) for patients harboring myelodysplastic syndromes with less than 5% marrow blasts (MDS-Lo). We analyzed the post-transplant outcomes of 1229 MDS-Lo patients who received myeloablative (MAC)(n = 651), reduced-intensity (RIC)(n = 397), and non-myeloablative conditioning (NMAC) regimens (n = 181). The multivariate analysis revealed that the RIC group had better chronic graft-versus-host disease (GVHD)- and relapse-free survival (CRFS) (P = 0.021), and GVHD- and relapse-free survival (GRFS) than the MAC group (P = 0.001), while no significant differences were observed between the NMAC and MAC groups. In the subgroup analysis, the MAC group has better overall survival (P = 0.008) than the RIC group among patients with an HCT-comorbidity index (HCT-CI) score of 0, while the RIC group had better overall survival (P = 0.029) than the MAC group among those with an HCT-CI score ≥3. According to the type of conditioning regimen, total body irradiation 12 Gy-based MAC regimen showed better OS and CRFS than the other MAC regimen, and comparable outcomes to the RIC regimen. In conclusion, the RIC and NMAC regimens are promising options for MDS-Lo patients in addition to the MAC regimen.
Subject(s)
Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Transplantation Conditioning , Humans , Transplantation Conditioning/methods , Myelodysplastic Syndromes/therapy , Myelodysplastic Syndromes/mortality , Retrospective Studies , Male , Female , Middle Aged , Adult , Hematopoietic Stem Cell Transplantation/methods , Japan , Aged , Prognosis , Transplantation, Homologous/methods , Adolescent , Young Adult , Societies, Medical , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Disease-Free Survival , AllograftsABSTRACT
Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potential curative therapeutic modality for advanced myelodysplastic syndrome (MDS). Within HCT, the advancement of cord blood transplantation (CBT) procedures has resulted in a drastic expansion of CBT as a donor source for MDS. However, data comparing matched sibling donors (MSDs) HCT with CBT for advanced MDS, which was defined as refractory anemia with an excess of blasts (RAEB)-1 and RAEB-2 according to the World Health Organization classification at the time of HCT, have not been explored. We retrospectively compared survival and other posttransplant outcomes in 999 adult patients with advanced MDS after receiving allogeneic HCT in Japan between 2011 and 2020, using either MSD (n = 331) or single-unit unrelated cord blood (UCB) (n = 668). In the multivariate analysis, there were no significant differences in overall survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.90-1.34; P = 0.347), disease-free survival (HR, 1.01; 95% CI, 0.84-1.23; P = 0.845), relapse (HR, 0.88; 95% CI, 0.68-1.15; P = 0.370), or non-relapse mortality (HR, 1.15; 95% CI, 0.87-1.50; P = 0.310) between MSD recipients and UCB recipients. UCB was significantly associated with lower neutrophil (HR, 0.28; 95% CI, 0.24-0.33; P < 0.001) and lower platelet (HR, 0.29; 95% CI, 0.23-0.36; P < 0.001) recovery compared to MSD. UCB was significantly associated with a lower incidence of chronic graft-versus-host disease (GVHD) (HR, 0.57; 95% CI, 0.44-0.75; P < 0.001) and extensive chronic GVHD (HR, 0.46; 95% CI, 0.32-0.67; P < 0.001) compared to MSD. Similar results were observed after adjusting for differences between MSD and UCB recipients by propensity score matching analysis. Our study demonstrated that single CBT and MSD HCT had similar survival outcomes for adult patients with advanced MDS despite the lower hematopoietic recovery in CBT recipients and higher chronic GVHD in MSD recipients.
Subject(s)
Anemia, Refractory, with Excess of Blasts , Cord Blood Stem Cell Transplantation , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Adult , Humans , Japan , Retrospective Studies , Siblings , Cord Blood Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Registries , Unrelated DonorsABSTRACT
Donor lymphocyte infusion (DLI) is a therapeutic modality for relapsed hematological malignancies after allogeneic hematopoietic stem cell transplantation. We retrospectively analyzed non-infectious pulmonary complications (non-IPCs) following DLI therapy in 41 post-transplant patients with hematological malignancies, and found that 7 developed post-DLI non-IPCs. The 6-year cumulative incidence of non-IPCs was 18.0%. In these patients, non-IPCs were classified into three subtypes: acute respiratory distress syndrome (ARDS), nonspecific interstitial pneumonia (NSIP), and bronchiolitis obliterans syndrome (BOS). The median intervals from the last date of DLI to the development of ARDS and BOS were 12 days (range, 12-14) and 9.4 months (range, 2.6-61.8), respectively; the intervals between DLI and the development of NSIP were 3.5 and 24.7 in 2 patients. Regarding the status of GVHD before the diagnosis with ARDS, 2 out of 3 patients showed the progression of acute GVHD following DLI therapy. One out of 2 patients with NSIP and all 3 patients with BO had chronic GVHD symptoms prior to the development of non-IPCs. In our cohort, 1 patient died of the progression of NSIP. In conclusion, the present study showed the clinical features of non-IPCs following DLI, suggesting the importance of careful follow-ups for non-IPCs in post-DLI patients.
Subject(s)
Graft vs Host Disease , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Respiratory Distress Syndrome , Humans , Graft vs Host Disease/etiology , Graft vs Host Disease/therapy , Lymphocyte Transfusion , Retrospective Studies , Neoplasm Recurrence, Local/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Hematologic Neoplasms/therapy , Lymphocytes , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapyABSTRACT
A 58-year-old man was diagnosed with mycosis fungoides (MF) confirmed by skin biopsy for systemic erythema that appeared in 2006 and had been on psoralen plus ultraviolet A (PUVA) therapy and topical steroids. In September 2017, he had diffuse large B-cell lymphoma and received chemotherapy. Since March 2019, tumor stage MF with large cell transformation was observed, and chemotherapy containing brentuximab vedotin (BV) was performed, which yielded a remarkable response. During the preparation for allogeneic hematopoietic stem cell transplantation, bradykinesia, delayed response, and cognitive decline were observed. Head magnetic resonance imaging fluid-attenuated inversion recovery images showed hyperintensity in the deep white matter below the bilateral frontal cortex. The general cerebrospinal fluid test revealed no abnormalities and was below the sensitivity of JC virus (JCV) quantitative PCR. As progressive multifocal leukoencephalopathy (PML) was strongly suspected from clinical symptoms and radiographic signs, ultrasensitive JCV testing was performed. The test result was positive; hence, the patient was diagnosed with PML. Chemotherapy was discontinued, but his central nervous system symptoms worsened, and he died on the 135th day of illness. We considered that PML developed based on the underlying disease and immunodeficiency caused by chemotherapy such as BV.
Subject(s)
JC Virus , Leukoencephalopathy, Progressive Multifocal , Mycosis Fungoides , Skin Neoplasms , Brentuximab Vedotin , Humans , Leukoencephalopathy, Progressive Multifocal/diagnosis , Leukoencephalopathy, Progressive Multifocal/etiology , Magnetic Resonance Imaging/adverse effects , Male , Middle Aged , Mycosis Fungoides/complications , Mycosis Fungoides/therapy , Skin Neoplasms/complications , Skin Neoplasms/drug therapyABSTRACT
Steroid-refractory acute graft-versus-host disease (SR-aGVHD) is a serious complication that negatively affects the prognosis and quality of life of patients who receive allogeneic hematopoietic stem cell transplantation (allo-HSCT). Antithymocyte globulin (ATG) is one of the second-line treatments for SR-aGVHD. We retrospectively evaluated Karnofsky Performance Status (KPS) recovery and clinical response in 11 patients who received the response-guided low-dose ATG treatment for SR-aGVHD after allo-HSCT using alternative donors. The median dose of ATG per cycle was 1.0 mg/kg (range, 1.0-1.25 mg/kg) and the median number of cycles of ATG was 2 (range, 1-4). The overall response rate was 63.6%, and the estimated overall survival rate at 1 year was 63.6%. Two out of seven patients who survived 1 year after the response-guided ATG treatment had KPS of 80 or higher. The remaining 5 patients had KPS of lower than 80 due to moderate chronic GVHD (cGVHD) and/or ≥grade 3 infectious complications. Based on the poor prognosis of patients with SR-aGVHD, the response-guided ATG treatment represents one therapeutic option. The present results also suggest that chronic GVHD and infectious complications after the response-guided ATG treatment were associated with decreased KPS recovery and impaired social function.
Subject(s)
Antilymphocyte Serum/therapeutic use , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation , Immunosuppressive Agents/therapeutic use , Acute Disease , Adolescent , Adult , Drug Resistance , Female , Graft vs Host Disease/diagnosis , Graft vs Host Disease/mortality , Humans , Karnofsky Performance Status , Male , Middle Aged , Steroids/therapeutic use , Survival Analysis , Transplantation, Homologous , Young AdultABSTRACT
Objective The standard treatment for chronic myeloid leukemia (CML) is the continuous use of tyrosine kinase inhibitors (TKIs), which results in a favorable prognosis for the majority of patients. Recent studies have identified cardiovascular diseases (CVDs) as late adverse events (AEs) related to TKIs. In this study, we evaluated the long-term efficacy and AEs of TKIs, focusing on CVDs. Methods We performed a retrospective survey of CML patients (diagnosed from 2001 to 2016) treated with TKIs in Nagasaki Prefecture. Clinical data were obtained from their medical records. We analyzed the survival, estimated cumulative incidence of CVDs, and risk factors for CVD among CML patients treated with TKIs. Results The overall survival rate of 264 CML patients treated with TKIs (median age 58 years old) was 89.6% [95% confidence interval (CI), 84.9-92.9%], and 80.5% (95% CI, 73.4-85.9%) at 5 and 10 years after the CML diagnosis, respectively. CVD events occurred in 26 patients (9.8%, median age 67.5 years old) with a median 65.5 months of TKI treatment. The cumulative incidences at 2 and 5 years was 2.4% (95% CI, 1.0-4.8%) and 5.2% (95% CI, 2.8-8.6%), respectively. Hypertension and a high SCORE chart risk at the diagnosis of CML were associated with CVD events during TKI treatment. Conclusion TKI treatment contributed to the long-term survival of CML patients in Nagasaki Prefecture in a "real-world" setting, but the incidence of CVDs seemed to be increased in these patients. A proper approach to managing risk factors for CVD is warranted to reduce CVD events during TKI treatment.
Subject(s)
Cardiovascular Diseases , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Aged , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/epidemiology , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Middle Aged , Protein Kinase Inhibitors/adverse effects , Retrospective Studies , Risk FactorsABSTRACT
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be curative for adult T-cell leukemia/lymphoma (ATL), but comorbidities increase transplant-related mortality. Here we report the outcome of allo-HSCT in a patient with ATL with human T-cell leukemia virus type I (HTLV-1)-associated myelopathy-tropical spastic paraparesis (HAM/TSP). A 48-year-old man was diagnosed with HAM/TSP and started prednisolone therapy. Ten years later, he developed lymphoma-type ATL. At the diagnosis of ATL, Osame's Motor Disability Score (OMDS) was 4. When prednisolone was gradually tapered and stopped following chemotherapy for ATL, HAM/TSP symptoms recurred (OMDS 7). Bone marrow transplantation from a human leukocyte antigen allele 8/8 matched unrelated donor was performed while ATL was in partial remission. Neutrophil engraftment with complete donor chimerism was achieved on day 19 after allo-HSCT. Mild gait improvement (OMDS 5) was observed on day 30. Although ATL relapsed on day 275, progression of HAM/TSP symptoms was not observed. Furthermore, there was no clear progression of HAM/TSP symptoms after donor lymphocyte infusions. The outcome of this case suggests that ATL patients with HAM/TSP tolerate allo-HSCT and donor lymphocyte infusions.
Subject(s)
HTLV-I Infections/complications , Hematopoietic Stem Cell Transplantation , Leukemia-Lymphoma, Adult T-Cell/complications , Leukemia-Lymphoma, Adult T-Cell/therapy , Spinal Cord Diseases/complications , Human T-lymphotropic virus 1/isolation & purification , Humans , Male , Middle Aged , Spinal Cord Diseases/virology , Transplantation, Homologous , Treatment OutcomeABSTRACT
Objective Classic Hodgkin lymphoma (CHL) has been regarded as a curable disease when treated appropriately, especially in younger patients, and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been regarded as the standard regimen. However, a relatively poor prognosis has been reported in older patients with CHL, and the efficacy and tolerability of the ABVD regimen has not been fully elucidated. We retrospectively investigated the outcomes in patients with CHL treated with ABVD at our institute. Methods Twenty-five patients were evaluated; 14 were ≤60 years of age, and 11 were >60 years of age (older group). Results The ABVD doses were reduced in all patients in the older group; the median average relative dose intensity was 0.58. In the older group, the 5-year overall survival (OS) and median OS were 100% and not reached, respectively, for patients with early-stage CHL and 66.7% and not reached, respectively, for those with advanced-stage CHL. No patients died of CHL, and only one treatment-related death was observed in the older group. Conclusion ABVD with dose attenuation may represent a feasible and effective strategy for the treatment of older patients with CHL in clinical practice, particularly in those with early-stage disease, although the optimal degree of attenuation remains unclear.
Subject(s)
Hodgkin Disease , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/therapeutic use , Child , Dacarbazine/therapeutic use , Doxorubicin/therapeutic use , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Humans , Neoplasm Staging , Retrospective Studies , Treatment Outcome , Vinblastine/therapeutic useABSTRACT
In the original publication of the article, the authors would like to alter the color of characters in the Supplemental Table 1 and 2.
ABSTRACT
Programmed death 1 ligand (PD-L1) is an immunomodulatory molecule expressed by cancer cells, and it has been widely demonstrated to inhibit host antitumor responses. The aim of the present study was to identify clinicopathological features associated with PD-L1 expression in the secondary solid cancers of patients after allogeneic hematopoietic stem cell transplantation. In this database of 530 patients who received allo-HSCT between 1990 and 2017, 15 developed solid cancers with a median interval of 3487 days after transplantation. Three patients had 2 different solid cancers. Eighteen solid cancer cases were identified. A multivariate analysis showed that chronic graft-versus-host disease (GVHD) was associated with an increased risk of solid cancer. The presence of chronic GVHD was observed in 8 out of 18 cases at the diagnosis of secondary malignancies. PD-L1 expression levels in cancers were significantly higher in patients with active chronic GVHD than in those without chronic GVHD (P = 0.020). Five cases of cancer that developed in the involved organs of chronic GVHD showed 30% or higher PD-L1 positivity. The present results revealed distinct PD-L1 expression in the secondary solid cancers of post-transplant patients with chronic GVHD.
Subject(s)
B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Gene Expression , Graft vs Host Disease/etiology , Graft vs Host Disease/genetics , Hematopoietic Stem Cell Transplantation/adverse effects , Neoplasms, Second Primary/etiology , Neoplasms, Second Primary/genetics , Adolescent , Adult , Female , Humans , Japan , Male , Middle Aged , Retrospective Studies , Risk , Transplantation, Homologous , Young AdultABSTRACT
Mogamulizumab (Mog) and lenalidomide (Len) are new therapeutic candidates for relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present study, we retrospectively analyzed 12 patients who received Mog or Len monotherapy for relapsed ATL after allo-HSCT. Eight and three patients received Mog and Len, respectively. The remaining patient received Mog for the first relapse and Len for the third relapse. A complete response was achieved by three and two patients who received Mog and Len, respectively, two and one of whom remained alive with a complete response for more than 20 months. In terms of adverse events, the emergence or progression of graft-versus-host disease was observed in three out of four patients treated with Len and in none of the patients treated with Mog. The development or progression of cytomegalovirus reactivation was detected in four out of eight patients treated with Mog and in none of those treated with Len. The present results suggest that Mog and Len would be promising treatment options for relapsed ATL after allo-HSCT and need to be selected based on adverse event profiles.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , Hematopoietic Stem Cell Transplantation/mortality , Lenalidomide/therapeutic use , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adult , Aged , Female , Follow-Up Studies , Humans , Leukemia-Lymphoma, Adult T-Cell/pathology , Leukemia-Lymphoma, Adult T-Cell/therapy , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Prognosis , Retrospective Studies , Salvage Therapy , Survival Rate , Transplantation, HomologousABSTRACT
Secondary pulmonary alveolar proteinosis (sPAP) is a complication of myelodysplastic syndrome (MDS). A 60-year-old woman was diagnosed with MDS with excess blasts-1. Fifty-four months after the initial diagnosis, treatment with azacitidine was initiated. Seventy-three months after the diagnosis, a bone marrow examination revealed increased myeloblasts, at which time computed tomography showed diffuse ground-glass opacities and interlobular septal thickening in the bilateral lower lung fields. A lung biopsy revealed the presence of PAP; therefore, the clinical diagnosis of MDS/sPAP was confirmed. Careful attention should be paid to the development of sPAP in MDS patients with pulmonary lesions during azacitidine treatment.
Subject(s)
Azacitidine/therapeutic use , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/drug therapy , Pulmonary Alveolar Proteinosis/etiology , Female , Humans , Middle Aged , Tomography, X-Ray ComputedABSTRACT
A 68-year-old male was diagnosed with acute promyelocytic leukemia (APL). A G-banding chromosomal analysis revealed the co-existence of two clones: one with del(20q) and t(15;17)(q22;q12) and another with del(20q) alone. During the remission of APL following treatment with all-trans-retinoic acid, del(20q) was persistently identified, indicating a diagnosis of cytogenetic abnormalities of undetermined significance (CCAUS) with isolated del(20q). Bicytopenia developed 48 months after the remission of APL. The presence of isolated del(20q) was detected in the G-banding analysis, whereas morphological dysplasia of hematopoietic cells was not confirmed. This case showed indolent progression from CCAUS after the remission of APL to clonal cytopenia of undetermined significance (CCUS). CCUS with isolated del(20q) persisted for 24 months without any finding of hematological malignancies. At the most recent follow-up, targeted capture sequencing showed the U2AF1 S34F mutation. Considerable attention needs to be paid in follow-ups for CCAUS with del(20q) after the treatment of leukemia.
Subject(s)
Chromosome Aberrations , Leukemia, Promyelocytic, Acute/diagnosis , Leukemia, Promyelocytic, Acute/genetics , Aged , Clone Cells , Follow-Up Studies , Humans , Leukemia, Promyelocytic, Acute/drug therapy , Male , Remission Induction , Tretinoin/therapeutic useABSTRACT
Ectopic soft tissue calcification (ESTC), a rare clinical condition, causes tissue and organ damage. It is associated with chronic renal failure, hyperparathyroidism, and malignant neoplasms, including multiple myeloma, and it is reportedly resistant to treatment. Here, we present the case of a 71-year-old male with multiple myeloma who had rapid ESTC in the lung. He had developed hypoparathyroidism secondary to thyroidectomy. During the course of our observation, he rapidly developed ectopic pulmonary calcification approximately 2 weeks after acquiring an infection. There was no evidence of further progression of multiple myeloma after the onset of ESTC, and treatment with ferric citrate hydrate and precipitated calcium resulted in immediate improvement of his pulmonary signs. We recommend cautious monitoring for patients with multiple myeloma and hypoparathyroidism to detect the onset of ectopic calcification. In addition, low blood phosphorus levels should be effectively treated.
Subject(s)
Calcinosis/etiology , Multiple Myeloma/complications , Parathyroidectomy/adverse effects , Aged , Humans , MaleABSTRACT
A 62-year-old male was diagnosed with blastic plasmacytoid dendritic cell neoplasm (BPDCN) with a MYC rearrangement. Four months after the first unrelated bone marrow transplantation (BMT), he developed the relapsed BPDCN. After the achievement of partial remission following re-induction therapy, he underwent a second BMT from another unrelated donor, and experienced complete remission with grade II acute graft-versus-host disease and moderate chronic graft-versus-host disease. He remains alive in complete remission more than 71 months after the second BMT. These results suggested that donor change at the second transplantation may represent a considerable therapeutic option for patients with relapsed BPDCN.
ABSTRACT
A 17-year-old male underwent a second bone marrow transplantation using a 6/8 allele HLA-matched unrelated donor. On day 100 after transplantation, steroid treatment for chronic graft-versus-host disease (GVHD) was started. On day 766, the patient experienced general fatigue, followed by double vision, ptosis, and dysphagia on day 810. Based on the positivity of the acetylcholine receptor antibody and a waning electromyography pattern, he was diagnosed with GVHD-related myasthenia gravis (MG). On day 861, we initiated plasmapheresis (PE), followed by the administration of intravenous immunoglobulin (IVIg) ; this treatment attenuated the bulbar symptoms of MG. Although the steroid treatment was continued, we restarted the administration of tacrolimus. On day 2,739 after transplantation, we stopped the steroid treatment, and the patient remained in remission for MG following the cessation of the steroid treatment on day 2,897. This case suggests that PE followed by IVIg could be an effective therapeutic alternative for MG associated with GVHD.
Subject(s)
Graft vs Host Disease , Myasthenia Gravis , Adolescent , Bone Marrow Transplantation , Graft vs Host Disease/complications , Humans , Immunoglobulins, Intravenous , Male , Myasthenia Gravis/etiology , PlasmapheresisABSTRACT
An adult woman developed polymorphic post-transplant lymphoproliferative disorder (PTLD) 58 months after unrelated cord blood transplantation. She was treated successfully with chemotherapy and radiation therapy but presented with lymphadenopathy and splenomegaly 74 months after transplantation. A lymph node biopsy confirmed the diagnosis of nodular sclerosis type Hodgkin lymphoma (classical Hodgkin lymphoma [CHL]-type PTLD). After salvage therapy and hematopoietic stem cell harvesting, she was subsequently treated with consolidative high-dose chemotherapy with melphalan followed by stem cell rescue, which resulted in durable remission. High-dose chemotherapy using stem cell rescue has potential as a therapeutic option for subsequent CHL-type PTLD.