Role of pretransplant interferon-alpha(IFN) treatment in the outcome of stem cell transplantation (SCT) from related donors in chronic myelogenous leukemia (CML): results from three Turkish transplant centers

Since transplantation cannot be performed immediately after the diagnosis of chronic myelogenous leukemia (CML), interferon treatment is usually required. This study aims to analyze the effects of interferon-alpha (IFN) treatment on allogeneic stem cell transplantation (SCT) outcome. A total of 106 patients aged 16-47 years and transplanted from HLA-identical sibling donors for CML in chronic phase (CP) were evaluated. In all, 48 had received IFN-alpha for a median duration of 5 months (1-18 months) until a median of 1 month prior to transplantation. Of the patients, 50 have received bone marrow transplant (BMT) whereas 56 have received peripheral blood stem cells (PBSCT) between 1991 and 1999 in three major transplant centers in Turkey. Patient characteristics in both groups were similar. More hematological responders were present in the IFN(+) patients (P=0.0001). No difference was found in engraftment kinetics. The incidences of acute or chronic graft-versus-host disease (GVHD), relapse and graft failure were similar in all patients regardless of stem cell source. Overall survival (OS) and disease-free survival (DFS) at 2 years were similar for both IFN(+) or (-) patients following SCT. With multivariate analysis, pretransplant IFN-alpha use, stem cell source, transplant year and CD34+ cell content were not found to be risk factors for OS. In conclusion, prior IFN exposure did not impair BMT or PBSCT outcome.     

Reduced risk of persisting cytomegalovirus pp65 antigenemia and cytomegalovirus interstitial pneumonia following allogeneic PBSCT

In order to evaluate the risk of cytomegalovirus (CMV) associated disease after allogeneic stem cell transplantation (SCT), 158 consecutive patients at risk for infection were analyzed. BMT was performed in 101 patients and peripheral blood stem cell transplantation (PBSCT) in 57 patients. CMV antigenemia was found in 57 cases (56%) after BMT and 27 cases (47%) after PBSCT, respectively. CMV antigenemia resistant to a 14-day course of GCV was found in 26 patients (26%) after BMT but in only four patients (7%) after PBSCT (P < 0.01). Eighteen patients (11%) developed CMV disease, 14 post BMT and four post PBSCT. Lethal CMV-related interstitial pneumonia (CMV-IP) occurred in 13 cases of whom 12 patients were bone marrow recipients (P = 0.04). The subgroup of seronegative patients with a CMV seropositive donor had a significantly lower risk of developing CMV antigenemia, GCV-resistant CMV antigenemia (P < 0.01) and CMV-related disease (P = 0.01). In conclusion, the incidence of persistent CMV antigenemia and CMV-IP was significantly reduced when allogeneic transplantation was performed with peripheral blood stem cells instead of bone marrow. These findings suggest that our previous in vitro data on improved immune reconstitution after allogeneic PBSCT as compared to allogeneic BMT have clinical relevance.     

T-cell-depleted peripheral blood stem cell transplantation for alpha-mannosidosis

Alpha-mannosidosis (alpha-mannosidosis) is a lysosomal storage disease characterized by accumulation of oligosaccharides in various tissues leading to symptoms such as coarse facial features, dysostosis multiplex, hearing disabilities, mental developmental delay and skeletal involvement (dysostosis multiplex). Without treatment, the severe infantile onset form of this autosomal recessive disease leads to progressive neurodegeneration and sometimes to early death. Stem cell transplantation has been shown to be an effective treatment. In the five patients published so far, correction of skeletal abnormalities and improvement of neuropsychological capabilities have been observed. We report the first patient who received a T-cell-depleted peripheral blood stem cell transplantation (PBSCT) for alpha-mannosidosis. The diagnosis of alpha-mannosidosis was made at the age of 14 months. At the age of 24 months, he underwent PBSCT with T-cell depletion by CD34-positive selection from his HLA phenotypically identical mother. Conditioning was carried out with busulfan (20 mg/kg), cyclophosphamide (200 mg/kg), OKT3 and methylprednisolone. The patient is alive and well 27 months after PBSCT and has made significant developmental progress. The pattern of urinary oligosaccharides has returned to almost normal. CD34-positive-selected PBSCT is a feasible option to reduce risk for GVHD for these patients.     

Syngeneic stem cell transplantation for HIV-related lymphoma

The treatment of human immunodeficiency virus (HIV)-related lymphoma is beset by a number of therapeutic limitations. High-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT) for relapsed disease is one option, but may be compromised by unacceptable treatment-related morbidity and mortality. We describe an HIV-positive male with relapsed immunoblastic non-Hodgkin's lymphoma (NHL) who successfully received salvage chemotherapy followed by a syngeneic PBSCT from his HIV-negative (hepatitis C positive) brother. At 15 months post-transplant he remains in complete remission with low-level HIV viral load, an improved CD4 lymphocyte count and absent anti-hepatitis C antibodies. We believe selected patients with relapsed HIV-related NHL should be considered for high-dose therapy.     

Membranous nephropathy following allogeneic peripheral blood stem cell transplantation in a boy with anaplastic large cell lymphoma

We report the case of 13-year-old boy who had been diagnosed as having anaplastic large cell lymphoma (ALCL) when he was 11 years old. He suffered a relapse despite the chemotherapy regimens he had been subjected to. Since anaplastic lymphoma kinase (ALK), one of the important prognostic factors of ALCL, was not expressed in the tumor cells, allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-matched elder brother was performed. Eleven months after PBSCT, the patient developed nephrotic syndrome as a consequence of chronic graft-versus-host disease (GVHD). He was diagnosed as having membranous nephropathy (MN) based on the results of histological examinations. Soluble interleukin-2 receptor and anti-nuclear antibody closely reflected the clinical course of MN, therefore some immune mechanisms closely related to chronic GVHD seemed to contribute to the occurrence of MN after PBSCT.     

Outcome from mechanical ventilation after autologous peripheral blood stem cell transplantation.

STUDY OBJECTIVE: To report the outcome of patients with autologous peripheral blood stem cell transplantation (PBSCT) receiving mechanical ventilation. DESIGN: Retrospective observational study. SETTING: Active hematopoietic stem cell transplantation center and a university hospital medical ICU. PATIENTS: Patients with autologous PBSCT receiving mechanical ventilation. METHOD: A review of the medical records of patients with autologous PBSCT receiving mechanical ventilation. Data collection was restricted to the first episode of mechanical ventilation. RESULTS: A total of 78 autologous PBSCT patients received mechanical ventilation for > 24 h. Twenty patients (26%) were extubated and discharged alive from the hospital. Thirteen hospital survivors (60%) were alive at 6 months. Lung injury (LI), vasopressor use, and hepatic and renal failure (HRF) were used to predict survival after mechanical ventilation. Sixty patients (76%) had no organ failure, or had isolated LI or only required treatment with vasopressors. Their hospital survival and 6-month survival were 32% and 20%, respectively. Hospital and 6-month survival for the patients with HRF or LI and vasopressor use was 6% and 0%, respectively. CONCLUSIONS: Prolonged mechanical ventilation and aggressive ICU support is justified for autologous PBSCT patients receiving mechanical ventilation with no organ failure, or who have only isolated LI, or who only require treatment with vasopressors.     

Four Cases of Desquamative Esophagitis Occurring after Hematopoietic Stem Cell Transplantation

We herein report four patients with desquamative esophagitis that developed one to nine days after peripheral blood stem cell transplantation (PBSCT). Three patients underwent allogeneic PBSCT for leukemia, and the other underwent autologous PBSCT for pineoblastoma. Esophagogastroduodenoscopy revealed mucosal sloughing and fresh blood in the esophagus. Fasting and intravenous proton pump inhibitor therapy in addition to blood transfusion improved the esophageal lesions within five to seven days in three patients. These cases indicate that desquamative esophagitis can occur in patients who receive hematopoietic stem cell transplantation. Although blood transfusions may be required, it can be resolved within seven days.     

T-cell receptor excision circles: a novel prognostic parameter for the outcome of transplantation in multiple myeloma patients

This study investigated whether T-cell receptor excision circles (TRECs) are a prognostic marker for the outcome of myeloma patients undergoing a tandem autologous peripheral blood stem cell transplantation (PBSCT). Twenty-five patients were enrolled. Samples were obtained at study enrollment, after conventional therapy, between first and second transplantation and 3, 6, 12 and 24 months after the second PBSCT. TRECs were quantified using real-time polymerase chain reaction. A high variation in TREC levels was found at diagnosis (median TREC level 136/10(5) peripheral blood mononuclear cells (PBMCs); range 1-1729), suggesting individual differences in thymic output of naive T cells. Patients with more than 136 TRECs/10(5) P BMCs at diagnosis had a statistically significant better overall survival (P=0.05) and event-free survival (P=0.045), whereas low TREC levels correlated with a higher incidence of infectious complications. Median TREC values were lowest after the first PBSCT (52/10(5) PBMCs) and reached the baseline 12 months after the second transplantation. Patients with high TREC levels after the second PBSCT had a significantly higher probability of being in complete or partial remission 30 months after the second PBSCT. TREC levels were not correlated with beta2-microglobulin and C-reactive protein levels at diagnosis. These data suggest that TRECs could be a relevant prognostic factor for patients who receive high-dose chemotherapy and autologous PBSCT.     

Syngeneic peripheral blood stem cell transplantation with brief immunosuppression for severe aplastic anemia

We report the cases of two severe aplastic anemia (SAA) patients who were successfully treated with syngeneic peripheral blood stem cell transplantation (PBSCT) using immunosuppression without high-dose chemotherapy or irradiation for conditioning. A 21-year-old woman with SAA of 6 years duration had been transfused heavily before transplantation and had developed refractory thrombocytopenia, chronic hepatitis and secondary hematochromatosis. Syngeneic PBSCT with immunosuppression using ATG, methylprednisolone, and cyclosporin-A was eventually performed without high-dose chemotherapy in September 1997. The second syngeneic PBSCT with the same immunosuppression was successfully performed in a 35-year-old male patient who had had SAA for 3 months in November 1998. Haemopoietic engraftment was rapid and sustained. There was no infection or mucositis during the syngeneic PBSCT. The patients are currently 9 to 22 months post-PBSCT without rejection. Our experience suggests that syngeneic PBSCT with brief immunosuppression is an effective alternative to pretransplant high-dose chemotherapy conditioning for SAA patients having syngeneic transplantation. Bone Marrow Transplantation (2000) 25, 337-339.     

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.     

POEMS syndrome treated with melphalan high-dose therapy and autologous blood stem cell transplantation: a single-institution experience

The acronym POEMS syndrome stands for a rare multi-system disorder, comprised of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. Here, we present a single-center report of a series of five POEMS patients treated with melphalan high-dose therapy (HDT) with subsequent autologous blood stem cell transplantation (ABSCT). After a median follow-up of 52 months from time of diagnosis (range, 15-192) and a median follow-up of 18 months after ABSCT (range, 11-120), all patients were alive. Overall, no severe transplantation-associated complications such as engraftment syndrome or peri- or post-transplant death were noted. In two cases, HDT followed by ABSCT resulted in a complete hematologic response; in the additional three cases, partial responses (PR) were achieved including one very good hematologic PR. Only one patient with initial PR developed progressive disease nearly 2.5 years after transplantation. Consequently, a second HDT with ABSCT was successfully applied resulting in clinical improvement and hematologic PR. In line with previous single-center reports, melphalan HDT followed by ABSCT proved to be a first-line treatment option with tolerable side effects in severely affected POEMS patients with progressing symptoms.     

Long-term outcomes after autologous stem cell transplantation for patients with POEMS syndrome (osteosclerotic myeloma): a single-center experience

The POEMS syndrome (polyradiculoneuropathy, organomegaly, multiple endocrinopathies, monoclonal protein, skin changes) is a rare disease associated with a plasma cell dyscrasia. Patients with disseminated POEMS can be treated with high-dose therapy and autologous stem cell transplantation (ASCT). While clinical improvement is nearly universal in these patients, the long-term outcomes after transplantation are unclear. We therefore assessed the long-term clinical outcomes of 59 POEMS patients treated with ASCT at our institution. With a median follow-up of 45 months, 14 patients have progressed with a progression-free survival of 98% and 75% at 1 and 5 years, respectively. Factors associated with progression have included an IgG-λ monoclonal component (hazard ratio [HR] 7.5; 95% confidence interval [CI], 2.3-28.3; P = .0008), fluorodeoxyglucose-avid lesions on baseline positron emission tomography (HR 6.4; 95% CI, 1.2-120; P = .03), lack of complete hematologic response (HR 5.4; 95% CI, 1.8-16.7; P = .003), and patients aged 50 years or younger at transplantation (HR 4.4; 95% CI, 1.3-20; P = .01). The most common progression events have been radiologic followed by rising VEGF. Symptomatic progression has been rare. Most patients could be salvaged with immunomodulatory drugs or radiation. The 5-year survival is 94%. Herein, we describe a system of monitoring response and progression among patients with POEMS after ASCT.     

Minimal change nephrotic syndrome after allogenic hematopoietic stem cell transplantation

We describe a 24-year-old man who developed minimal change nephrotic syndrome after allogenic hematopoietic stem cell transplantation (HSCT). One year after undergoing allogenic peripheral blood stem cell transplantation (PBSCT), this patient presented with proteinuria. He also presented with skin and lip lesions considered to be chronic graft-versus host disease. Observation of renal biopsy specimens by light microscopy revealed minor glomerular abnormalities. However, electron microscopy disclosed focal mesangial interposition, irregular thickening of the glomerular basement membrane and subendothelial loosening. Two years after HSCT, the patient developed nephrotic syndrome. Long use of cyclosporine improved the proteinuria and hypoalbuminemia within 12 months.     

Successful treatment with splenectomy and interferon alpha against recurred hemophagocytic syndrome in remission state of anaplastic large cell lymphoma following high-dose therapy and autologous peripheral blood stem cell transplantation

A 25-yr-old man had been diagnosed as having CD30(+) anaplastic large cell lymphoma associated with hemophagocytic syndrome (HS). He received aggressive frontline chemotherapies and consolidation with autologous peripheral blood stem cell transplantation (PBSCT) following high-dose chemotherapy combined with splenic irradiation (720 cGy in fraction of 180 cGy). However, HS recurred on day 50 of PBSCT without radiologic evidence of lymphoma relapse. On day 56 of PBSCT, splenectomy was performed and pathology showed massive sinusoidal infiltration of histiocytes. On day 68 of PBSCT, administration of interferon alpha was started and maintained for 24 months. HS was completely resolved and he has been alive well and in complete remission (CR), 60 months after initial diagnosis.     

Transient improvement of left ventricular function after peripheral blood stem cell transplantation in a patient with myelodysplastic syndrome and dilated cardiomyopathy.

A patient who had myelodysplastic syndrome (MDS) and dilated cardiomyopathy (DCM) had a transient improvement of cardiac function after peripheral blood stem cell transplantation (PBSCT). When he was admitted to hospital for PBSCT, a chest X ray showed cardiomegaly, and Tc-99m quantitative gated single photon emission computed tomography (QGS) showed increases in left ventricular (LV) volumes and a decrease in LV ejection fraction (LVEF). A coronary angiogram showed no evidence of coronary artery disease. Left ventriculography showed similar findings as QGS, and the findings from a myocardial biopsy were compatible with DCM. Three months after a successful allo-PBSCT with his brother as the donor, the cardiomegaly had been attenuated, the LV volumes decreased and LVEF increased on the QGS images. However, 10 months later, his cardiac function had deteriorated. The changes in cardiac function did not correlate with the hematological changes, such as the hemoglobin level.     

Factors influencing platelet transfusion refractoriness in patients undergoing allogeneic hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation has been considered a risk factor for development of platelet transfusion refractoriness. The objective of this study was to assess the platelet transfusion refractoriness rate in patients undergoing allogeneic hematopoietic stem cell transplantation from different sources. We retrospectively reviewed the charts and transfusion records of patients who underwent allogeneic stem cell transplantation at our institution between 2013 and 2015. The evaluation of post-transfusion platelet count was assessed for each transfusion given, from day of progenitor infusion to day 30 after transplantation. Of 167 patients included in this study, 101 received peripheral blood stem cell transplantation (PBSCT) and 66 received umbilical cord blood transplantation (UCBT). Overall, the percentage of platelet transfusions with a 14-h CCI lower than 5000 was 59.3%, being these data significantly higher for UCBT (67.6%) than for PBSCT (31.0%). Seventy-eight percent of patients underwent UCBT become refractory, while 38.6% of patients who received PBSCT were refractory. Factors associated to platelet refractoriness were lower CD34+ cell dose infused, higher number of antibiotics used, presence of anti-HLA I antibodies, and reduced-intensity conditioning regimen. Platelet refractoriness is a frequent and complex adverse event and remains a therapeutic challenge in the management of patients undergoing HSCT. There is a higher rate of platelet refractoriness in patients who received UCBT as compared to patients who received PBSCT.     

Secondary solid tumors in autologous-peripheral blood stem cell transplantation recipients

We investigated the incidence of post-transplant solid tumors in a cohort of 109 patients who had undergone auto-peripheral blood stem cell transplantation (PBSCT) for acute myelogenous leukemia (n = 18), acute lymphoblastic leukemia (n = 7), non-Hodgkin's lymphoma (n = 52), Hodgkin's disease (n = 5), multiple myeloma (n = 16), chronic myelogenous leukemia (n = 1), myelodysplastic syndrome (n = 3) and solid tumors (n = 7). The patients were followed up for a median of 32 months after PBSCT. Five second solid malignancies developed in 4 patients within 14 to 43 months after PBSCT: large cell carcinoma of the lung, adenocarcinoma of the rectum, cholangiocellular carcinoma of the liver, squamous cell carcinoma of the mouth, and adenocarcinoma of the gallbladder. The affected patients were 3 of 52 with non-Hodgkin's lymphoma and one of 16 with multiple myeloma. One of the patients was in the 5th decade of life (n = 31) and 3 were in the 6th decade (n = 31). The cumulative actuarial risk for developing post-transplant solid tumors was 8% at 8 years. Elderly patients (> or = 60 year old) who have undergone PBSCT need to be observed carefully for second neoplasms because of their increased risk of post-transplant solid tumors.     

Successful non-myeloablative allogeneic peripheral blood stem cell transplantation (PBSCT) for Waldenström's macroglobulinemia with severe pancytopenia

We report a 62-year-old male who underwent non-myeloablative allogeneic peripheral blood stem cell transplantation (PBSCT) because of his life-threatening severe pancytopenia due to refractory Waldenstr?m's macroglobulinemia. This therapy was performed safely and he made a marked recovery from his cytopenia that had not been improved with any other therapy. Bone marrow aspirates showed post-transplant mixed chimerism during engraftment, and became completely donor-derived after a series of GVHD symptoms, without subsequent donor lymphocyte infusion. Our results suggest that non-myeloablative allogeneic PBSCT could be a good alternative for patients suffering from multi-drug resistant Waldenstr?m's macroglobulinemia.     

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.