scholarly journals Variable clinical manifestations of hematopoietic stem cell transplant-associated thrombotic microangiopathy

2018 ◽  
Vol 2 (4) ◽  
pp. 253-256
Author(s):  
Chenguang Jia ◽  
Maoquan Qin ◽  
Bin Wang ◽  
Guanghua Zhu ◽  
Yan Yan
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Thrombotic Microangiopathy ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Clinical Manifestations ◽  
Cell Transplant ◽  
Hematopoietic Stem

Thrombotic Microangiopathy with Tacrolimus/Sirolimus-Based GVHD Prophylaxis Regimen in Patients Undergoing Hematopoietic Stem Cell Transplant from a Matched Unrelated Donor

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 797-797 ◽  
Author(s):  
Tam Khuu ◽  
Sepideh Shayani ◽  
Joycelynne Palmer ◽  
Roberto Rodriguez ◽  
Pablo Miguel Parker ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Thrombotic Microangiopathy ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Increased Risk

Abstract Thrombotic microangiopathy (TMA) is a multifactorial complication of related and unrelated allogeneic hematopoietic stem cell transplant (allo-HSCT). The true incidence of TMA is difficult to estimate due to lack of agreement on a single definition. Diagnosis is often complicated by multiple potential etiologies for the clinical findings. Sirolimus (SIR), an inhibitor of mammalian target of Rapamycin (mTOR), is a novel immunosuppressive agent that works synergistically with calcineurin inhibitors (CNI) to prevent graft-versus-host disease (GVHD) in allo-HSCT. Recently, the addition of SIR to CNIs was reported to result in a higher than expected incidence (10.8%) of TMA (Cutler et al. BBMT2005; 11:551–7). We evaluated the incidence and risk factors for TMA in a cohort of patients undergoing matched unrelated (MUD) HSCT using SIR combined with tacrolimus (TAC) and mini-methotrexate for GVHD prophylaxis at City of Hope. TMA was defined as SCr increase of ≥ 50% above baseline, LDH twice the institutional upper normal limit, presence of schistocytes or persistent presence of nucleated red blood cells, and prolonged or progressive thrombocytopenia (platelets <50 × 109/L or ≥ 50% decrease from previous count). A case series of 47 MUD-HSCT patients were included in this retrospective chart review study. The median age was 50 years (range: 19–67); (male/female: 28/19). Conditioning regimens consisted of fludarabine/melphalan (65%) and FTBI combined with cyclophosphamide or etoposide (35%). Diagnoses included ALL (32%), AML (25%), NHL (15%), MDS (15%), MPD (9%), CML (2%), CLL (2%). Twenty-six patients (55%) had a 10/10 matched (HLA-A, B, C, DRB1, and DQB1) donor by high-resolution on typing. The median follow up for the 30 surviving patients is 14.5 months (2.8–26). The one-year probabilities of overall survival and non-relapse mortality (NRM) were 61% and 19%, respectively. Grade II-IV acute GVHD (aGVHD) was reported in 60% of all patients (grade III-IV: 25%). Thirteen (28%) patients met the above diagnostic criteria for TMA. In addition, we included two patients who did not meet the criteria due to missing tests but were clinically diagnosed with TMA by independent attending physicians, resulting in the total incidence of 32% (15/47). Four of the 15 patients met the criteria for TMA as a result of ongoing multi-organ failure secondary to other causes. The median time to TMA onset was five weeks (2–20 weeks). Most cases (93%) occurred within the first 100 days post-HSCT. Thirteen patients developed both TMA and aGVHD, in which the majority of patients (70%) developed TMA after a diagnosis of aGVHD had been made. Initial treatments for TMA included holding TAC (33%), holding SIR (20%), holding or adjusting doses (27% and 20%, respectively) for both drugs. One patient underwent plasma exchange. Sixty percent of patients subsequently recovered from TMA as defined by normalization of laboratory values. Of the 17 expired patients, ten were diagnosed with TMA. Causes of death were as follows: for TMA cases, relapse mortality=3, NRM=7; for Non-TMA patients, relapse mortality=6, NRM=1. At the time of TMA diagnosis, the median TAC and SIR levels were 11.3 (0–18.8) and 7 (0–23.9) ng/ml, respectively, in contrast to the median TAC and SIR levels for non-TMA patients at 6.1 (p= 0.02) and 5.5 (p=0.13) ng/ml, respectively. To identify other possible risk factors for TMA, the following patient and treatment-related characteristics were examined: age, conditioning regimen, disease type, degree of HLA match, and exposure to triazole antifungals. Only higher tacrolimus levels (HR: 6.9, p<0.01) and aGVHD grades III-IV (HR: 3.5, p=0.02) were associated with an increased risk for TMA. In conclusion, TMA is common after MUD allo-HSCT using SIR-containing GVHD prophylaxis. The risk factors for TMA suggest that careful monitoring and adjustment of TAC/SIR dosages to avoid super-therapeutic levels is critical, particularly during ongoing GVHD.

scholarly journals Cryptococcosis in Hematopoietic Stem Cell Transplant Recipients: A Rare Presentation Warranting Recognition

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Carolina Firacative ◽  
Silvia Katherine Carvajal ◽  
Patricia Escandón ◽  
Jairo Lizarazo
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Clinical Manifestations ◽  
Central Nervous System Involvement ◽  
Cell Transplant ◽  
Adequate Treatment ◽  
Hematopoietic Stem ◽  
Cryptococcal Disease

Cryptococcosis, a life-threatening mycosis caused mainly by Cryptococcus neoformans, appears to be distinctly rare in hematopoietic stem cell transplant (HSCT) recipients. When it occurs, this fungal infection is a major limitation for a successful transplant. This review comprehensively analyses 24 cases, reported in the literature, of patients with haematological malignancies including leukemias, multiple myeloma, and lymphomas, as indication for HSCT, who presented with cryptococcosis after transplantation. Of the 24 cases, 11 each occurred in patients receiving allogeneic and autologous stem cell transplants, from bone marrow, peripheral blood, and umbilical cord blood. HSCT recipients were slightly more often male, and the age of the patients ranged from 12 to 74 years. Antifungal prophylaxis was reported in most cases. Clinical manifestations of cryptococcal disease included more frequently central nervous system involvement followed by fungaemia, disseminated infection, pulmonary cryptococcosis, cerebellitis, and diarrhea. Diagnosis differed depending on the clinical presentation but habitually included cryptococcal antigen assay, India ink, and culture. Notably, not only C. neoformans but also C. albidus, C. terreus, C. laurentii, and C. adeliensis were identified as the causal species, the last two including strains resistant to fluconazole. Amphotericin B, alone or in combination, was the most common antifungal drug used for the treatment of cryptococcosis in HSCT recipients. Due to the small number of cases, it was not possible to establish if mortality rate, which was the same as survival rate, depends on the effect of the immunosuppressive regimen, the site of cryptococcal infection, and/or the antifungal therapy used to control the mycosis. Although uncommon, the recognition of cryptococcal disease in stem cell transplant is essential for a timely and adequate treatment, improved prognosis, reduced morbidity and mortality, and successful transplantation.

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