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2.
Ann Hematol ; 103(6): 2059-2072, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38662207

ABSTRACT

Myelodysplastic syndrome (MDS) is well known to be complicated by systemic inflammatory autoimmune disease (SIADs). However, it remains unclear how the prognosis after allogenic hematopoietic stem cell transplantation (allo-HSCT) in patients with MDS is impacted by SIADs that occur before allo-HSCT. Therefore, we hypothesized that SIADs before allo-HSCT may be a risk factor for negative outcomes after allo-HSCT in patients with MDS. We conducted a single-center, retrospective, observational study of sixty-nine patients with MDS or chronic myelomonocytic leukemia who underwent their first allo-HCT. Fourteen of the patients had SIADs before allo-HSCT. In multivariate analysis, the presence of SIADs before allo-HSCT was an independent risk factor for overall survival (HR, 3.36, 95% confidence interval: 1.34-8.42, p = 0.009). Endothelial dysfunction syndrome was identified in five of 14 patients with SIADs who required immunosuppressive therapy or intensive chemotherapy, and notably, all patients with uncontrollable SIADs at allo-HSCT developed serious endothelial dysfunction syndrome and died in the early phase after allo-HSCT. The development of SIADs in the context of MDS is thought to reflect the degree of dysfunction of hematopoietic cells in MDS and suggests a higher risk of disease progression. In addition, MDS patients with SIADs before allo-HSCT are considered to be at higher risk of endothelial dysfunction syndrome because of preexisting vascular endothelial dysfunction due to SIADs. In conclusion, SIADs before allo-HSCT constitute an independent risk factor for death in MDS patients undergoing allo-HSCT.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myelomonocytic, Chronic , Myelodysplastic Syndromes , Humans , Female , Male , Leukemia, Myelomonocytic, Chronic/mortality , Leukemia, Myelomonocytic, Chronic/therapy , Myelodysplastic Syndromes/therapy , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/complications , Middle Aged , Hematopoietic Stem Cell Transplantation/adverse effects , Retrospective Studies , Risk Factors , Adult , Aged , Autoimmune Diseases/mortality , Autoimmune Diseases/therapy , Transplantation, Homologous/adverse effects , Allografts , Survival Rate
3.
Ann Hematol ; 103(5): 1705-1715, 2024 May.
Article in English | MEDLINE | ID: mdl-38494552

ABSTRACT

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT), and stratification of the high-risk group before transplantation is significant. Serum autotaxin (ATX) levels have been reported to increase in patients with liver fibrosis caused by metabolic inhibition from liver sinusoidal endothelial cells. Considering that the pathophysiology of VOD/SOS begins with liver sinusoidal endothelial cell injury, an increase in serum ATX levels may precede the onset of VOD/SOS. A retrospective study with 252 patients, including 12 patients with VOD/SOS, who had received allo-HCT was performed. The cumulative incidence of VOD/SOS was higher in the group with serum ATX levels before conditioning (baseline ATX) above the upper reference limit (high ATX group, p < 0.001), and 1-year cumulative incidences were 22.7% (95% confidence interval [95%CI], 3.1-42.4%) and 3.5% (95%CI, 1.1-5.8%), respectively. In the multivariate analysis, elevated baseline ATX was identified as an independent risk factor for VOD/SOS development and showed an additive effect on the predictive ability of known risk factors. Furthermore, the incidence of VOD/SOS-related mortality was greater in the high ATX group (16.7% vs. 1.3%; p = 0.005). Serum ATX is a potential predictive marker for the development of VOD/SOS.


Subject(s)
Hematopoietic Stem Cell Transplantation , Hepatic Veno-Occlusive Disease , Humans , Hepatic Veno-Occlusive Disease/epidemiology , Hepatic Veno-Occlusive Disease/etiology , Retrospective Studies , Endothelial Cells , Hematopoietic Stem Cell Transplantation/adverse effects , Risk Factors
4.
Acta Haematol ; 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38432202

ABSTRACT

INTRODUCTION: The graft-versus-leukemia effect of HLA-B leader dimorphism, i.e. methionine (M) or threonine (T) at position -21 of the leader sequence, has been observed in HLA-haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (PTCy-haplo). However, the biological mechanism has been unclear, and the contributions of HLA-B leader genotype to risk reduction of relapse might be dependent on posttransplant cyclophosphamide (PTCy) doses. METHODS: To investigate whether the effect of HLA-B leader dimorphism was modified by the PTCy dose, we retrospectively analyzed 99 patients who received PTCy-haplo. RESULTS: In the low-dose PTCy group, the patient M+ HLA-B leader genotype did not significantly affect the cumulative incidence of relapse (CIR) but negatively impacted the overall survival (OS) compared to the M- genotype. In contrast, in the high-dose PTCy group, patients with the M+ genotype had a decreased CIR, but no significant difference in the OS was observed between patients with the M+ and M- genotypes. Regardless of PTCy doses, the patient M+ genotype had detrimental effects on nonrelapse mortality. CONCLUSION: Our findings suggest that the effect of the patient HLA-B leader genotype is modified by the PTCy dose, providing immunological insight into the PTCy dosage and supporting further studies to investigate the underlying mechanisms.

6.
Int J Hematol ; 119(3): 316-326, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38252235

ABSTRACT

Hepatomegaly is an extramedullary disease (EMD) manifestation of hematological malignancy. Although EMD before allogeneic hematopoietic stem cell transplantation (allo-HCT) is a risk factor for relapse in patients not in complete remission (NonCR) patients, the significance of hepatomegaly to allo-HCT is unclear. We conducted a single-center retrospective observational study of 140 patients with acute leukemia and myelodysplastic syndrome who underwent allo-HCT at our institution from 2014 to 2019. Hepatomegaly was assessed by ultrasonography using the liver index (LI). In the univariable analysis, the LI/height ratio was significantly associated with relapse (hazard ratio [HR] per standard deviation [sd]: 1.51, 95% confidence interval [CI] 1.18-1.93, p = 0.001, sd = 13.8) in NonCR patients (n = 62), but showed no significant association in CR patients (n = 78) (HR per sd: 0.95, 95% CI 0.64-1.39, p = 0.780, sd = 8.7). In multivariable analysis, the LI/height ratio was significantly associated with relapse (HR per sd: 1.34, 95% CI 1.02-1.78, p = 0.037) after adjusting for the refined disease risk index and conditioning intensity. Interaction analysis showed a noteworthy but not statistically significant association between the LI/height ratio and CR status (p = 0.110). In conclusion, our findings suggest that the LI may be a risk factor for relapse in NonCR patients after allo-HCT.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Humans , Hepatomegaly/etiology , Transplantation, Homologous , Transplantation Conditioning , Myelodysplastic Syndromes/therapy , Myelodysplastic Syndromes/pathology , Leukemia, Myeloid, Acute/pathology , Retrospective Studies , Recurrence , Chronic Disease
7.
Transpl Immunol ; 82: 101988, 2024 02.
Article in English | MEDLINE | ID: mdl-38185390

ABSTRACT

BACKGROUND: No comparative data have shown significant survival differences between HLA-mismatched unrelated donor (MMUD) transplantation and cord blood (CB) transplantation, each with reduced-intensity/reduced-toxicity conditioning (RIC/RTC). However, advances in graft-versus-host disease (GVHD) prophylaxis might help update current strategies. METHODS: We retrospectively compared the outcomes of first allogeneic hematopoietic cell transplantation from MMUDs (n = 15) or single unrelated CB (n = 35) after RIC/RTC. RESULTS: The median age was 60 years. The MMUD group had a numerically lower 100-day incidence of grade III-IV acute GVHD (7% vs. 29%, P = 0.079) and non-relapse mortality (0% vs. 40%, P = 0.12). Eight MMUD recipients received anti-thymocyte globulin, bortezomib, or posttransplant cyclophosphamide for GVHD prophylaxis. They did not develop grade III-IV acute GVHD. The MMUD group had significantly better 5-year overall survival than the CB group (62% vs. 31%, P = 0.021), although relapse rates were similar. A multivariable analysis and sensitivity analysis also showed trends toward higher overall survival in the MMUD group. CONCLUSION: MMUD with better GVHD prophylaxis might be preferred over CB in patients with older age and comorbidities.


Subject(s)
Cord Blood Stem Cell Transplantation , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Middle Aged , Unrelated Donors , Cord Blood Stem Cell Transplantation/adverse effects , Retrospective Studies , Transplantation, Homologous/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/prevention & control , Graft vs Host Disease/etiology , Cyclophosphamide , Transplantation Conditioning
8.
J Epidemiol ; 34(3): 137-143, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-37211396

ABSTRACT

BACKGROUND: Glomerular hyperfiltration has been reported to be associated with adverse renal outcomes in the general population. It is not known whether drinking pattern is associated with the risk of glomerular hyperfiltration in healthy individuals. METHODS: We prospectively followed middle-aged 8,640 Japanese men with normal renal function, no proteinuria, no diabetes, and no use of antihypertensive medications at entry. Data on alcohol consumption were gathered by questionnaire. Glomerular hyperfiltration was defined as estimated glomerular filtration rate (eGFR) ≥117 mL/min/1.73 m2, which was the upper 2.5th percentile value of eGFR in the entire cohort. RESULTS: During 46,186 person-years of follow-up, 330 men developed glomerular hyperfiltration. In a multivariate model, for men who consumed alcohol on 1-3 days per week, alcohol consumption of ≥69.1 g ethanol/drinking day was significantly associated with the risk of glomerular hyperfiltration (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.18-4.74) compared with non-drinkers. For those who consumed alcohol on 4-7 days per week, higher alcohol consumption per drinking day was associated with a higher risk of glomerular hyperfiltration: the HRs for alcohol consumption of 46.1-69.0, and ≥69.1 g ethanol/drinking day were 1.55 (95% CI, 1.01-2.38), and 1.78 (95% CI, 1.02-3.12), respectively. CONCLUSION: For high drinking frequency per week, more alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration, while for low drinking frequency per week, only very high alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration in middle-aged Japanese men.


Subject(s)
Alcohol Drinking , Kidney Diseases , Middle Aged , Male , Humans , Japan/epidemiology , Prospective Studies , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Kidney Diseases/epidemiology , Glomerular Filtration Rate , Ethanol , Risk Factors
9.
Transplant Cell Ther ; 30(3): 316.e1-316.e12, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38108263

ABSTRACT

Allogeneic hematopoietic cell transplantation (allo-HCT) is the sole curative therapy for myelodysplastic syndrome (MDS). In the absence of an HLA-matched sibling donor, an HLA-matched unrelated donor (MUD) is considered the leading candidate. However, in recent decades, the alternative donor pool has been extended to HLA-haploidentical donors, especially with the development of graft-versus-host disease (GVHD) prophylaxis using post-transplantation cyclophosphamide (PTCy). Comparative data for haploidentical and MUD allo-HCT in patients with MDS are scarce. We retrospectively analyzed 697 adult patients with MDS who underwent HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with PTCy (n = 136), MUD bone marrow transplantation (MUD-BMT) (n = 465), or MUD peripheral blood stem cell transplantation (MUD-PBSCT) (n = 96) as their first allo-HCT between 2014 and 2020 using Japanese registry data. Multivariable analyses demonstrated faster neutrophil engraftment (hazard ratio [HR], 2.19; 95% confidence interval [CI], 1.65 to 2.90; P < .001) and platelet engraftment (HR, 2.31; 95% CI, 1.72 to 3.10; P < 0001) in the MUD-PBSCT cohort compared with the haplo-PBSCT cohort. MUD-BMT was associated with a higher incidence of grade II-IV acute GVHD than haplo-PBSCT (HR, 1.52; 95% CI, 1.00 to 2.29; P = .048). Among patients without in vivo T cell depletion using antithymocyte globulin (ATG) (haplo-PBSCT, n = 136; MUD-BMT, n = 446; MUD-PBSCT, n = 65), MUD-PBSCT recipients experienced faster hematopoietic recovery, MUD-BMT recipients (HR, 1.54; 95% CI, 1.02 to 2.32; P = .042) or MUD-PBSCT recipients (HR, 1.83; 95% CI, 1.06 to 3.18; P = .03) had a higher incidence of grade II-IV acute GVHD, and MUD-PBSCT recipients developed chronic GVHD more frequently than haplo-PBSCT recipients (HR, 1.74; 95% CI, 1.04 to 2.89; P = .034). There were no significant differences in overall survival, disease-free survival, GVHD-free relapse-free survival, relapse, or nonrelapse mortality in the haplo-PBSCT cohort versus the MUD-BMT or MUD-PBSCT cohorts. In conclusion, despite differences in the incidences of hematopoietic engraftment and GVHD depending on graft type and ATG use in MUD transplant recipients, major transplantation outcomes were comparable between recipients of haplo-PBSCT using PTCy and recipients of MUD-BMT or MUD-PBSCT.


Subject(s)
Graft vs Host Disease , Myelodysplastic Syndromes , Peripheral Blood Stem Cell Transplantation , Adult , Humans , Peripheral Blood Stem Cell Transplantation/adverse effects , Unrelated Donors , Retrospective Studies , Cyclophosphamide/therapeutic use , Graft vs Host Disease/prevention & control , Myelodysplastic Syndromes/therapy
11.
Blood Coagul Fibrinolysis ; 34(6): 419-422, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37577920

ABSTRACT

Acquired hemophilia A (AHA) is a rare, life-threatening hemorrhagic disease caused by autoantibodies against factor VIII (FVIII), and bypassing agents (BPA) are used to control bleeding. However, some cases need a change of BPA or BPAs given sequentially or in combination for refractory bleeding. A 71-year-old man was admitted with subcutaneous hemorrhage. Laboratory investigations showed prolongation of activated partial thromboplastin time (APTT) and low-coagulation FVIII activity and FVIII inhibitor; we, therefore, diagnosed AHA. He was treated with recombinant factor VIIa (rFVIIa) BPA and prednisolone. However, his symptoms did not improve sufficiently, thus we switched BPA to activated prothrombin complex concentrate. Unfortunately, this was not effective and he suffered hemorrhagic shock. Therefore, we selected rFVIIa, with plasma-derived FVIIa and factor X (pd-FVIIa/FX) as combination therapy, and hemostasis was achieved without thrombosis. This case suggests that the combination of rFVIIa and pd-FVIIa/FX short-term can be well tolerated for refractory hemorrhage in AHA.


Subject(s)
Factor VIIa , Hemophilia A , Male , Humans , Aged , Hemophilia A/complications , Hemophilia A/drug therapy , Factor X/therapeutic use , Hemorrhage/etiology , Hemorrhage/complications , Factor VIII/therapeutic use , Recombinant Proteins/therapeutic use , Recombinant Proteins/pharmacology
12.
J Infect Chemother ; 29(9): 909-912, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37207959

ABSTRACT

Sinusoidal obstruction syndrome (SOS) is a fatal complication after hematopoietic stem cell transplantation (HSCT). Only a few complications after HSCT have been reported as risk factors for SOS, including sepsis. Here, we report the case of a 35-year-old male diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent peripheral blood HSCT from a human leukocyte antigen-matched unrelated female donor in remission. Graft-versus-host disease prophylaxis contained tacrolimus, methotrexate, and low-dose anti-thymoglobulin. The patient was treated with methylprednisolone for engraftment syndrome from day 22. On day 53, he presented worsening fatigue, breathlessness, and abdominal pain in the right upper quadrant that had persisted for 4 days. Laboratory tests showed severe inflammation, liver dysfunction, and positive for Toxoplasma gondii PCR. He died on day 55. An autopsy showed SOS and disseminated toxoplasmosis. Hepatic infection with T. gondii was identified in zone 3 of the liver, which overlapped with the pathological features of SOS. In addition, the timing of the exacerbation of hepatic dysfunction coincided with the onset of systemic inflammatory symptoms and T. gondii reactivation. This rare case of toxoplasmosis is the first to suggest that hepatic infection with T. gondii is strongly associated with SOS after HSCT.

13.
Acta Haematol ; 146(4): 338-342, 2023.
Article in English | MEDLINE | ID: mdl-37088083

ABSTRACT

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has been widely used and is highly effective for B-cell lymphoid malignancies. Immune-mediated adverse effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occur in the acute phase and are monophasic after CAR T-cell therapy. However, late-onset inflammatory and neurological toxicities have not been well studied. We encountered a patient with recurrent late-onset inflammatory toxicities and progressive dysautonomia after CD19-directed CAR T-cell therapy. A 69-year-old man was treated with CD19-directed CAR T-cell therapy for transformed follicular lymphoma. Triphasic inflammation with stomatitis, cytopenia, and noninfectious pneumonia was first observed 7 months after CAR T-cell infusion. Progressive dysautonomia was also observed and eventually fatal. Residual CAR T cells, predominantly central memory CD4+ cells, were detectable in peripheral blood approximately 1 year after CAR T-cell infusion. The cytokine profile with the lack of tumor necrosis factor-α, interferon-γ, and interleukin-1ß elevation in the peripheral blood and cerebrospinal fluid was inconsistent with that of typical CRS or ICANS. The persistence of central memory CD4+ CAR T cells might be associated with unique manifestations of late-onset immune-mediated adverse effects. More cases should be accumulated to elucidate the mechanism and establish the optimal management strategy of late-onset immune-mediated toxicities previously unrecognized.


Subject(s)
Lymphoma, Follicular , Lymphoma, Non-Hodgkin , Receptors, Chimeric Antigen , Male , Humans , Aged , Neoplasm Recurrence, Local , Immunotherapy, Adoptive/adverse effects , CD4-Positive T-Lymphocytes , Antigens, CD19
14.
Exp Hematol ; 123: 56-65, 2023 07.
Article in English | MEDLINE | ID: mdl-37098360

ABSTRACT

Posttransplant cyclophosphamide (PTCy) is an effective prophylaxis for graft-versus-host disease (GVHD) due to its suppression of donor-derived alloreactive T cells in allogeneic hematopoietic stem cell transplantation (HSCT). The graft-versus-leukemia (GVL) effect is an antileukemia effect induced by donor-derived alloreactive T cells, similar to GVHD, whereas no studies have demonstrated the association between the dynamics of donor-derived alloreactive T cells and impairment of the GVL effect after HSCT with PTCy. We herein evaluated the dynamics of donor-derived T cells expressing a functional marker for alloreactivity, programmed cell death-1 (PD-1), in a murine HSCT model with PTCy. We showed that PTCy was associated with the development of leukemia cells and the decreased survival probability in an HSCT model with leukemia cells, whereas PTCy could ameliorate GVHD and increased the survival probability in the HSCT model without leukemia cells. We revealed that the percentages of PD-1 expressing donor-derived CD8+/CD4+ alloreactive T cells, with the exception of CD44+ memory T cells, in the recipient spleen were suppressed with PTCy, and that donor T-cell chimerism levels were decreased early after HSCT with PTCy. Our results suggest that PTCy correlated with the impairment of the GVL effect and the amelioration of GVHD through the suppression of PD-1 expressing donor-derived CD8+/CD4+ alloreactive T cells after HSCT.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia , Mice , Animals , T-Lymphocytes , Transplantation, Homologous , Programmed Cell Death 1 Receptor , Hematopoietic Stem Cell Transplantation/methods , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Cyclophosphamide/pharmacology , Cyclophosphamide/therapeutic use , Leukemia/drug therapy
16.
Transplant Proc ; 55(3): 706-710, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36934053

ABSTRACT

Stenotrophomonas maltophilia is known to be an opportunistic pathogen with intrinsic and acquired resistance mechanisms to multiple antibiotics. Bloodstream infection caused by S. maltophilia is a potentially fatal complication, especially in recipients of umbilical cord blood transplantation (CBT). Infrequent reports of S. maltophilia skin and soft tissue infections (SSTIs), including metastatic cellulitis and ecthyma gangrenosum, have been reported as wound infections. Metastatic cellulitis lesions due to S. maltophilia are typically reported to be tender, erythematous, and to show warm subcutaneous infiltration. There are only a few available reports about the clinical course of metastatic cellulitis due to S. maltophilia. We experienced a case involving the development of metastatic cellulitis with fulminant and extensive exfoliation in a patient who underwent CBT. Despite controlling the bloodstream infection caused by S. maltophilia, the patient succumbed to secondary fungal infection due to the devastation of the skin barrier. Our case highlights that SSTIs due to S. maltophilia can cause the unexpected development of fulminant metastatic cellulitis with systemic epidermal peeling in severely immunocompromised hosts, including CBT recipients undergoing steroid therapy.


Subject(s)
Cord Blood Stem Cell Transplantation , Fungemia , Gram-Negative Bacterial Infections , Stenotrophomonas maltophilia , Humans , Cellulitis/complications , Cellulitis/drug therapy , Candida parapsilosis , Fungemia/complications , Fungemia/drug therapy , Cord Blood Stem Cell Transplantation/adverse effects , Anti-Bacterial Agents/therapeutic use , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/drug therapy
17.
Exp Clin Transplant ; 21(2): 184-188, 2023 02.
Article in English | MEDLINE | ID: mdl-36919727

ABSTRACT

Salvage human leukocyte antigen-haploidentical hematopoietic cell transplant using posttransplant cyclophosphamide has shown promising results for graft failure in various hematological disorders. However, to our knowledge, no such findings have been reported for a case of chronic active Epstein-Barr virus infection, although graft failure is relatively common in patients with chronic active Epstein-Barr virus infection. We report a case of a 32-year-old woman with natural killer-cell type chronic active Epstein-Barr virus infection who experienced graft failure after a first allogeneic hematopoietic cell transplant from an unrelated human leukocyte antigen-matched donor.The patientreceived a second allogeneic hematopoietic cell transplant with human leukocyte antigen-haploidentical hematopoietic cell transplant using posttransplant cyclophosphamide (cyclophosphamide, 50 mg/kg, on day 3 and day 4) following reduced-intensity conditioning as rescue therapy. Neutrophils successfully engrafted on day 19, and the patient sustained remission without severe transplant-related complication 10 months after salvage human leukocyte antigen- haploidentical hematopoietic cell transplant using posttransplant cyclophosphamide. This report suggests that salvage human leukocyte antigen- haploidentical hematopoietic cell transplant using posttransplant cyclophosphamide may be a feasible therapeutic option for graft failure in patients with chronic active Epstein-Barr virus infection.


Subject(s)
Epstein-Barr Virus Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Female , Humans , Adult , Hematopoietic Stem Cell Transplantation/adverse effects , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/therapy , Graft vs Host Disease/etiology , Herpesvirus 4, Human , Cyclophosphamide , HLA Antigens , Transplantation Conditioning/methods
18.
Transpl Immunol ; 77: 101792, 2023 04.
Article in English | MEDLINE | ID: mdl-36682572

ABSTRACT

Donor lymphocyte infusion (DLI) is a curable treatment option, inducing a graft-versus-tumor effect in patients with relapsed hematological malignancies after allogeneic hematopoietic cell transplantation (allo-HCT). However, not only graft-versus-host disease but also pulmonary complications are problematic adverse events after DLI. Although viral infections can be associated with pulmonary complications after DLI, the mechanism underlying these complications remains unclear. Detecting the causative virus infections after pulmonary complications following DLI is challenging, as invasive examinations, such as bronchoalveolar lavage and lung biopsies, are necessary. Family Picornaviridae, including Human-Rhinovirus (HRV) and Enterovirus (EnV), can induce fatal lower respiratory tract infection (LRTI) in recipients who undergo allo-HCT, which can be underdiagnosed. We encountered a 62-year-old man with relapsed myelodysplastic syndrome 20 days after a second HLA-haplo-identical allo-HCT and 4 DLI procedures who was later found to have HRV and EnV LRTI by postmortem electron microscopy. Despite high-dose immunosuppression, severe hypoxemia did not improve, and he succumbed to respiratory failure. Immunosuppressive therapy for idiopathic pneumonia syndrome after allo-HCT may be effective, but its efficacy for acute respiratory failure after DLI is controversial. Our case indicated that the control of viral replication should be prioritized over that of inflammation in HRV and EnV LRTI after DLI.


Subject(s)
Enterovirus , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Respiratory Tract Infections , Male , Humans , Middle Aged , Rhinovirus , Transplantation, Homologous , Neoplasm Recurrence, Local/etiology , Myelodysplastic Syndromes/therapy , Myelodysplastic Syndromes/etiology , Respiratory Tract Infections/etiology , Graft vs Host Disease/pathology , Lymphocytes/pathology , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Lymphocyte Transfusion/methods
19.
Blood ; 141(16): 1971-1981, 2023 04 20.
Article in English | MEDLINE | ID: mdl-36626583

ABSTRACT

In the phase 3 POLARIX study in previously untreated diffuse large B-cell lymphoma, polatuzumab vedotin combined with rituximab plus cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) significantly improved progression-free survival (PFS) compared with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with similar safety. Patients were randomized 1:1 to 6 cycles of Pola-R-CHP or R-CHOP plus 2 cycles of rituximab alone. For registration of POLARIX in China, consistency of PFS in an Asia subpopulation (defined as ≥50% of the risk reduction in PFS expected in the global population) was evaluated. Overall, 281 patients were analyzed: 160 patients from Asia in the intention-to-treat (ITT) population of the global study and 121 from an ITT China extension cohort. Of these, 141 were randomized to Pola-R-CHP and 140 to R-CHOP. At data cutoff (28 June 2021; median follow-up 24.2 months), PFS met the consistency definition with the global population, and was superior with Pola-R-CHP vs R-CHOP (hazard ratio, 0.64; 95% confidence interval [CI], 0.40-1.03). Two-year PFS was 74.2% (95% CI, 65.7-82.7) and 66.5% (95% CI, 57.3-75.6) with Pola-R-CHP and R-CHOP, respectively. Safety was comparable between Pola-R-CHP and R-CHOP, including rates of grade 3 to 4 adverse events (AEs; 72.9% vs 66.2%, respectively), serious AEs (32.9% vs 32.4%), grade 5 AEs (1.4% vs 0.7%), AEs leading to study treatment discontinuation (5.0% vs 7.2%), and any-grade peripheral neuropathy (44.3% vs 50.4%). These findings demonstrate consistent efficacy and safety of Pola-R-CHP vs R-CHOP in the Asia and global populations in POLARIX. This trial was registered at https://clinicaltrials.gov/ct2/home as # NCT03274492.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Lymphoma, Large B-Cell, Diffuse , Humans , Rituximab/adverse effects , Prednisone/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/adverse effects , Vincristine/adverse effects , Doxorubicin/adverse effects , Lymphoma, Large B-Cell, Diffuse/therapy
20.
Transpl Immunol ; 77: 101781, 2023 04.
Article in English | MEDLINE | ID: mdl-36603700

ABSTRACT

Eosinophilic gastrointestinal disorders (EGIDs) are infrequent complications after allogeneic hematopoietic cell transplantation (allo-HCT). Furthermore, it is well-known that allergic diseases are transferable after allo-HCT from allergic donors to non-allergic recipients. However, the type of graft-versus host disease (GVHD) prophylaxis that leads to allergic disease transfer is unclear. Furthermore, no study has reported a case of acquired food allergy resulting in EGID that was detected based on the clinical course and the detection of antigen-specific immunoglobulin E after allo-HCT. We encountered two patients with acute leukemia accompanied by eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE) due to newly appearing food allergy after cord blood transplantation (CBT) with T-cell non-depletion GVHD prophylaxis. Despite having no history of allergic disease, the patients experienced allergic symptoms due to dairy products (Case 1) and eggs (Case 2) after CBT. They subsequently experienced severe nausea, heartburn, and anorexia (Case 1) and diarrhea (Case 2). Cases 1 and 2 were diagnosed with EoE and EGE, respectively, based on endoscopic and histological examinations. Dietary treatment without steroids improved the symptoms in both cases. These cases highlight that the unexpected transfer of food allergy after CBT can lead to EGIDs, especially in patients receiving T-cell non-depletion GVHD prophylaxis.


Subject(s)
Cord Blood Stem Cell Transplantation , Enteritis , Eosinophilic Esophagitis , Food Hypersensitivity , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Cord Blood Stem Cell Transplantation/adverse effects , Enteritis/complications , Enteritis/diagnosis , Eosinophilic Esophagitis/complications , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Food Hypersensitivity/therapy , Food Hypersensitivity/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology
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