Virological, clinical, and ophthalmologic features of cytomegalovirus retinitis after hematopoietic stem cell transplantation.

We identified 10 patients who developed cytomegalovirus (CMV) retinitis after HSCT during a 14-year period. The median day of diagnosis of CMV retinitis after transplantation was day 251 (range, days 106--365). CMV retinitis was associated with CMV serostatus of donor or recipient (P=0.01), CMV reactivation before day 100 (P=0.007), delayed lymphocyte engraftment (P<0.05), and chronic graft versus host disease (GVHD; P<0.001). In allogeneic recipients of HSCT who were alive at day 100 after transplantation and had chronic clinical extensive GVHD, the incidence of GVHD was 1.4% (8 of 577). Five of 10 patients had other manifestation of CMV disease before retinitis occurred (4 with gastrointestinal disease and 1 with interstitial pneumonia; median time, 70 days before onset of CMV retinitis; range, 58--279 days), and 4 others had CMV excretion. CMV retinitis was bilateral in 4 patients; 9 of 10 patients had ocular symptoms (i.e., decreased vision and floaters). Six of 7 patients responded well to ganciclovir or foscarnet systemic treatment, 1 improved only after switching to cidofovir, and 1 patient who received a transplant in 1983 did not respond to acyclovir treatment. In conclusion, CMV retinitis is an uncommon late complication after HSCT that occurs mainly in seropositive allograft recipients with previous CMV reactivation and chronic GVHD, and with delayed engraftment of lymphocytes.     

Epidemiology and outcomes of Clostridium difficile infections in hematopoietic stem cell transplant recipients

Background.?Clostridium difficile is the leading cause of infectious diarrhea among hospitalized patients and is a major concern for patients undergoing hematopoietic stem cell transplantation (HSCT). Risk factors and the natural history of C. difficile infection (CDI) are poorly understood in this population. Methods.?We performed a retrospective nested case-control study to describe the epidemiology, timing, and risk factors for CDI among adult patients who received HSCTs at our center from January 2003 through December 2008. Results.?The overall 1-year incidence of CDI was 9.2% among HSCTs performed (n?=?999). The median time to diagnosis of CDI was short among both autologous and allogeneic HSCT recipients (6.5 days and 33 days, respectively). Risk factors for CDI in allogeneic HSCT recipients included receipt of chemotherapy prior to conditioning for HSCT, broad-spectrum antimicrobial use, and acute graft-versus-host disease (GVHD; adjusted odds ratio [AOR], 4.45; 95% confidence interval [CI], 1.54-12.84; P?=?.006). There was a strong relationship between early CDI and subsequent development of gastrointestinal tract GVHD in the year following allogeneic HSCT (P?相似文献   

Gastric antral vascular ectasia:clinical presentation and therapeutic management

The gastric antral vascular ectasia (GAVE) or watermelon stomach is an increasingly recognized cause of persistent upper gastrointestinal bleeding, which has typical endoscopic and histological findings. This disease is most frequent in elderly women, and several associated conditions have been well established. Some patients with severe portal hypertensive gastropathy may have a GAVE like appearence. Nevertheless, a correct diagnosis is relevant in order to choose an appropiate treatment. The objective of the current study is to analyze the clinical features and treatment of a group of patients with GAVE evaluated at our Institution. A review of the current literature was also performed. Six women and three men with GAVE were admitted at the Buenos Aires British Hospital between November 1998 and January 2004. Endoscopic biopsy was performed in eight patients and was consistent with GAVE in all cases. Four patients with chronic anaemia as unique manifestation were successfully treated with iron supplements. Endoscopic treatment was performed in 4 patients, 3 of them were treated with bipolar electrocautery and 1 with argon plasma coagulation. An antrectomy was carried out in the ninth patient. The resolution of the bleeding was observed in all cases with the different therapeutics options used.     

Prevalence and natural history of gastric antral vascular ectasia in patients undergoing orthotopic liver transplantation

GOALS: To describe the prevalence and natural history of gastric antral vascular ectasia (GAVE) in patients with end-stage liver disease undergoing orthotopic liver transplantation (OLT). BACKGROUND: GAVE is a well-recognized cause of gastrointestinal hemorrhage. Although 30% of patients with GAVE have liver disease, the prevalence of GAVE in patients with cirrhosis is not known. STUDY: We reviewed clinical records of patients who underwent OLT at our institution from February 1, 1998 to June 2003. Demographic and clinical details were recorded with attention to findings during upper endoscopy before and after OLT. RESULTS: A total of 597 patients underwent OLT, and 345 were evaluated preoperatively with esophagogastroduodenoscopy (EGD). Eight (2.3%) were found to have GAVE before OLT. Three of these eight underwent EGD after OLT, and GAVE was absent in all three. None of the patients with GAVE experienced gastrointestinal bleeding postoperatively. CONCLUSIONS: GAVE was present in nearly 1 in 40 patients with end-stage liver disease who underwent EGD before OLT at our institution and appears to resolve after transplant. These findings are consistent with a previous report documenting resolution of GAVE after OLT.     

Progressive interstitial fibrosis of the lung in sclerodermoid chronic graft-versus-host disease

Sclerodermoid chronic graft-versus-host disease (sGVHD) is a well-known complication in patients with a long history of chronic GVHD. Pulmonary involvement in chronic GVHD presents typically as bronchiolitis obliterans (BO). Pulmonary fibrosis after allogeneic hematopoietic stem cell transplantation (HSCT) is presumed to be caused by the long-term toxicity of the conditioning regimen or the result of lung injury elicited predominantly by viral infections or GVHD. We present two patients with late onset pulmonary fibrosis associated with moderate sGVHD of the skin after HSCT. At the initial diagnosis of chronic GVHD both patients presented with symptoms of interstitial pneumonia. Years later both patients developed moderate to severe interstitial pulmonary fibrosis in association with sGVHD. One patient showed additional clinical and histological signs of BO. While one patient responded to increased immunosuppression including total nodal irradiation (1 Gy), the other patient died due to complications related to pulmonary fibrosis.     

Effect of endoscopic treatment of gastric antral vascular extasia associated with chronic liver disease

Background : Gastric antral vascular ectasia (GAVE), as a cause of upper gastrointestinal bleeding, has been treated surgically, endoscopically and pharmacologically for the past 20 years. Methods : We analyzed the clinical effect of endoscopic treatment for 12 cases of GAVE diagnosed at Osaka National Hospital between January 1993 and October 1998. Results : Eight of the 12 cases were treated endoscopically due to marked anemia and histories of gastrointestinal bleeding. All had chronic liver disease (CLD). Mean age was 69 years on diagnosis. Male to female ratio was 1 : 1. Gastric antral vascular ectasia was a cause of 3.9% of bleeding associated with CLD. The modes of endoscopic treatment of the eight cases were laser photocoagulation (1), electrocautery (3), and heater probe thermocoagulation (4). The initial treatment required an average of 5.1 sessions over a period of 43 days. Initial hemostasis was successful in all cases. Treatments for recurrent bleeding were necessary in six cases within 9.2 months, and endoscopic coagulation was again effective in two cases. Corticosteroids were effective in two of three cases resistant to endoscopic therapy. Mean follow‐up period after initial treatment was 2.8 years. The mean total number of therapeutic endoscopy sessions was 9.6. Conclusion : Endoscopic treatments and/or corticosteroids have yielded sufficient results in the hemorrhage of GAVE. Factors affecting the recurrence of GAVE need to be analyzed in CLD patients.     

Gastric Antral Vascular Ectasia as a Cause of Anemia in Systemic Sclerosis

We describe a patient with systemic sclerosis (SSc) in whom chronic blood loss from gastric antral vascular ectasia (GAVE) presented a major problem. A 69‐year‐old man, with Raynaud's phenomenon, sclerodactyly, hyperpigmentation on the forehead and nailfold capillary dilatation, required repeated transfusions but still exhibited persistent anemia due to recurrent upper gastrointestinal bleeding. He did not have cutaneous telangiectasias; neither hereditary hemorrhagic telangiectasia of Osler–Weber–Rendu disease nor any collagen disease was reported in his family. Gastroendoscopy showed an array of intensely red stripes radiating to the pylorus, resembling the stripes of a watermelon, with oozing hemorrhages. Biopsy samples were taken from this region of the distal gastric antrum and showed foveolar hyperplasia and superficial vascular ectasia, consistent with GAVE. Endoscopic treatment with a heater probe unit was effective in controlling blood loss from GAVE. The patient tolerated the procedure well and there were no resultant complications. Five sessions of treatment resulted in an eradication of almost all the vascular lesions, as well as negative fecal occult blood test results and a marked improvement of anemia without further transfusions. GAVE should be a diagnostic consideration in patients with SSc who develop recurrent upper gastrointestinal bleeding and anemia.     

Giardiasis in a hematopoietic stem cell transplant patient

Giardiasis can mimic diarrhea secondary to mucosal injury from the conditioning therapy prior to hematopoietic stem cell transplant (HSCT), as well as from graft‐versus‐host disease (GVHD). Herein, we describe the endoscopic diagnosis of giardiasis in a patient 2 months after HSCT for myelodysplastic syndrome. The patient was referred to gastroenterology service for suspected GVHD, but duodenal biopsy results showed Giardia lamblia. He was successfully treated with metronidazole with prompt resolution of all of his gastrointestinal symptoms. This case highlights the need to consider giardiasis in the differential diagnosis of diarrhea in the peri‐transplant period.     

Reduced-intensity conditioning using fludarabine and antithymocyte globulin alone allows stable engraftment in a patient with dyskeratosis congenita

Dyskeratosis congenita (DC) is a rare inherited disorder characterized by the triad of nail dystrophy, mucosal leukoplakia, and reticular pigmentation. Bone marrow failure is the principal cause of early mortality, and stem cell transplantation is the only cure for these patients. However, the results of conventional hematopoietic stem cell transplantation (HSCT) for patients with DC are poor because of the high incidence of transplant-related complications. We describe the successful treatment of a 21-year-old male with DC by nonmyeloablative HSCT from a matched unrelated donor. The gene responsible for the X-linked form of DC was screened and hemizygosity for the mutation Gln31Lys was found, which is consistent with the diagnosis. The conditioning regimen consisted of only fludarabine and antithymocyte globulin. Additionally, a graft-versus-host disease (GVHD) prophylaxis was administered with cyclosporine A (CSA) and mycophenolate mofetil (MMF). The regimen was well tolerated, no severe posttransplantation complications were observed, and engraftment was rapid and complete (granulocytes on day +11 and platelets on day +13). Seven months after HSCT, the patient developed GVHD of the liver after tapering CSA which was successfully treated with prednisolone, CSA, and MMF. At the time of reporting, 3 years after HSCT, the patient remained in good clinical condition with minimal signs of chronic GVHD of the oral mucosa. Thus, we conclude that a low-intensity conditioning regimen might be sufficient to induce permanent engraftment by using matched unrelated donor HSCT in DC patients and may avoid severe organ toxicity. Although allogeneic HSCT in patients with DC will not cure the underlying genetic defect it may significantly prolong survival through effective therapy for hematologic complications.     

Acute polymyositis after donor lymphocyte infusion

Polymyositis usually occurred along with other manifestations of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) had been reported. However, polymyositis with a sole manifestation of acute GVHD following donor lymphocyte infusion (DLI) is rare. We reported a 45-yr-old man of acute lymphoid leukemia post-allogeneic HSCT 6 months developed acute polymyositis after DLI. He did not develop any symptoms, signs of acute or chronic GVHD following allogeneic HSCT, despite withdraw of immuosuppresive agents, cyclosporin A (CsA). As the DNA-STR of bone marrow analysis showed mixed chimerism, he received the DLI for remission on May 16, 2002. Acute polymyositis developed following DLI 22 d later. The clinical presentation of polymyositis is compatible with a manifestation of acute GVHD following DLI. It also responds to the treatment of steroid and CsA.     

Treatment of gastropathy and gastric antral vascular ectasia in patients with portal hypertension

Opinion statement Portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) are two distinct gastric mucosal lesions that may cause acute and/or chronic upper gastrointestinal hemorrhage in patients with cirrhosis. Whereas PHG is associated with portal hypertension, GAVE may present in patients without portal hypertension or liver disease. Diagnosis is made upon visualization of the characteristic lesions with upper gastrointestinal endoscopy, although the differential may be difficult at times. PHG is characterized endoscopically by a mosaic pattern with or without red signs and a proximal distribution. PHG mainly causes chronic blood loss and anemia in patients with cirrhosis but also can cause acute hemorrhage. First-line therapy for chronic hemorrhage from PHG is a nonselective β-blocker (propranolol or nadolol) and iron supplementation. If bleeding/anemia are not controlled with these measures and the patient is transfusion-dependent, shunt therapy (transjugular intrahepatic portosystemic shunt [TIPS] or shunt surgery) should be considered. Management of acute bleeding from PHG, an infrequent event, should be accomplished with a vasoactive drug, somatostatin (or its analogues) or terlipressin. If bleeding responds, the patient must be switched to a nonselective β-blocker. Shunt therapy should be considered in patients who rebleed or continue to bleed despite adequate β-blocker therapy. GAVE is less common than PHG. It is characterized by red spots without a background mosaic pattern, typically in the gastric antrum. When lesions have a linear distribution, the lesion is called “watermelon stomach.” GAVE is a cause of chronic gastrointestinal bleeding and anemia in patients with cirrhosis. If lesions are localized, first-line therapy is argon plasma coagulation. In more diffuse lesions, therapy with argon plasma coagulation is more complicated. Preliminary data suggest that cryotherapy may be a reasonable option for diffuse GAVE lesions. Neither β-blockers nor TIPS reduces the bleeding risk in patients with GAVE and thus should not be used in this setting.     

Polymyositis after donor lymphocyte infusion

Chronic graft-versus-host disease (GVHD) is a common long-term complication of allogeneic hematopoietic stem-cell transplantation (HSCT), and is responsible for morbidity, mortality and a decrease in quality of life of patients after SCT. Polymyositis, which usually co-occurs with other manifestations of GVHD, has previously been reported. However, polymyositis as the sole manifestation of chronic GVHD following donor lymphocyte infusion (DLI) is rare. We report a 30-year-old man with Hodgkin's lymphoma who developed acute polymyositis following treatment by DLI 4?months post-allogeneic HSCT. The patient developed fever and generalized myalgia 22?days after a single dose of DLI. Laboratory testing showed elevated muscle enzymes and myopathic abnormalities on electromyographic examination. Muscle biopsy showed features of acute polymyositis, with widespread foci of muscle fiber necrosis associated with infiltration of small mononuclear cells. Twenty-four hours after diagnosis, the patient developed a fatal ventricular arrhythmia. Cardiac involvement may occur in association with polymyositis, but usually occurs in elderly patients after several months of illness. The present case highlights the importance of systematic cardiac evaluation when a diagnosis of polymyositis is initially made to exclude this infrequent presentation of chronic GVHD characteristically associated with some HLA-DR haplotypes.     

Gastric antral vascular ectasia (watermelon stomach) in patients with systemic sclerosis

This report describes 5 patients with systemic sclerosis (SSc) who developed severe, recurrent upper gastrointestinal (GI) bleeding due to gastric antral vascular ectasia (GAVE). The clinical records, the endoscopic findings, and the histologic appearance of biopsy specimens and surgically resected gastric tissue from the patients were reviewed. All 5 patients developed severe and recurrent episodes of upper GI bleeding leading to severe anemia requiring multiple transfusions. The cutaneous involvement was diffuse in 3 patients and limited in 2. All but 1 had cutaneous telangiectasias. The diagnosis of GAVE was established by endoscopy within 3 years of the diagnosis of SSc in all cases. One patient required heater probe cautery, 2 required laser coagulation, and 2 underwent surgical resection of the gastric antrum for control of the GI bleeding. The possibility of GAVE should be considered in SSc patients who have recurrent upper GI bleeding. It is suggested that the antral vascular lesions in these patients may represent a component of the spectrum of vascular alterations of SSc.     

Endoscopic diagnosis of gastrointestinal graft-versus-host disease

AIM：To evaluate the diagnostic value of endoscopy in patients with gastrointestinal graft-versus-host disease （GI GVHD）. METHODS：We identified 8 patients with GI GVHD following allogeneic hematopoietic stem cell trans-plantation （HSCT）. GVHD was defined histologically as the presence of gland apoptosis, not explained by other inflammatory or infectious etiologies. RESULTS：The symptoms of GI GVHD included anorexia, nausea, vomiting, watery diarrhea, abdominal pain, GI bleeding, etc. Upper endoscopic appearance varied from subtle mucosal edema, hyperemia, erythema to obvious erosion. Colonoscopic examination showed diffuse edema, hyperemia, patchy erosion, scattered ulcer, sloughing and active bleeding. Histological changes in GI GVHD included apoptosis of crypt epithelial cells, dropout of crypts, and lymphocytic infiltration in epithelium and lamina propria. The involvement of stomach and rectocolon varied from diffuse to focal. CONCLUSION：Endoscopy may play a significant role in early diagnosis of GI GVHD patients following allogeneic HSCT, and histologic examination of gastrointestinal biopsies is needed to confirm the final diagnosis.     

Gastric antral vascular ectasia (GAVE): an update on clinical presentation, pathophysiology and treatment

Gastric antral vascular ectasia (GAVE), though a rare disorder, causes up to 4% of non-variceal upper GI bleeding. This paper gives an overview of studies examining clinical presentation and pathophysiology, and reviews the current evidence for invasive and non-invasive treatments. GAVE is often associated with systemic illnesses, such as cirrhosis of the liver, autoimmune connective tissue disorders, bone marrow transplantation and chronic renal failure. The pathophysiological changes leading to GAVE have not been fully explained and remain controversial. Patient presentation varies from chronic iron-deficiency anaemia to heavy acute gastrointestinal bleeding. It is important to differentiate GAVE from portal hypertensive gastropathy as GAVE does not respond to measures reducing portal pressures. Endoscopic ablation (Nd:YAG-laser or argon plasma coagulation) is the first-line treatment of choice. As evidence for pharmacological therapy with oestrogen (and/or progesterone), tranexamic acid or thalidomide stems from case reports only, these should be used if endoscopic measures have failed to stop chronic blood loss. Surgical antrectomy should be reserved for unresponsive cases as it is associated with a high mortality. Ultimately, treatment of the underlying medical co-morbidities may lead to resolution of GAVE.     

Squamous cell carcinoma of the tongue complicating chronic oral mucosal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Two patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia. Chronic graft-versus-host disease (GVHD) developed, with persistent symptomatic oral lesions. At 2 and 6 years post-HSCT, both patients developed squamous cell carcinoma (SCC) of the tongue in areas previously involved by chronic GVHD. None had any known risk factor for SCC. Histologically, moderate to severe dysplasia was present in noncancerous oral mucosa. Oral SCC is rarely described after HSCT, and a review of the reported cases showed chronic GVHD to be a common risk, suggesting that the chronic inflammation associated with GVHD might be of pathogenetic significance.     

Second Allogeneic Hematopoietic Stem Cell Transplantation for Leukemia Relapse After First Allogeneic Transplantation: Outcome of 16 Patients in a Single Institution

Sixteen patients who underwent a second allogeneic hematopoietic stem cell transplantation (HSCT2) for leukemia relapse after the first allogeneic transplantation (HSCT1) were studied. The patients included 7 patients with acute myelogenous leukemia, 8 with acute lymphoblastic leukemia, and 1 with chronic myelogenous leukemia. The median patient age at HSCT2 was 22 years (range, 12 to 44 years). The median interval between HSCT1 and HSCT2 was 19 months (range, 2 to 46 months). At HSCT2, 7 patients were in complete remission (CR), 7 had relapsed, and 2 had bone marrow aplasia. In 14 patients, donors for HSCT2 were the same as those for HSCT1. Two donors were replaced, 1 for another HLA-matched sibling and 1 for an unrelated cord blood donor. Four patients (25%) died within 100 days after HSCT2 from veno-occlusive disease, sepsis, interstitial pneumonitis, or chronic graft-versus-host disease (GVHD), without leukemia relapse. Seven patients (44%) developed leukemia relapse and died between 4 and 20 months after HSCT2. Five patients (31%) survived beyond 4 years. One patient died from chronic GVHD without leukemia relapse 55 months after HSCT2. The 4 other patients were alive between 79 and 134 months after HSCT2 (median follow-up, 106 months). Factors that favorably influenced survival were age younger than 20 years and CR duration after HSCT1 longer than 12 months. HSCT2 is considered to be beneficial for select patients. Preparative regimens, GVHD prophylaxis, and donor choice for HSCT2 need to be studied to obtain a more successful outcome for HSCT2.     

The addition of sirolimus to the graft‐versus‐host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial

Inhibition of the mechanistic target of rapamycin (mTOR) pathway has clinical activity in lymphoma. The mTOR inhibitor sirolimus has been used in the prevention and treatment of graft‐versus‐host disease (GVHD) after allogeneic haematopoietic stem cell transplantation (HSCT). A retrospective study suggested that patients with lymphoma undergoing reduced intensity conditioning (RIC) HSCT who received sirolimus as part of their GVHD prophylaxis regimen had a lower rate of relapse. We therefore performed a multicentre randomized trial comparing tacrolimus, sirolimus and methotrexate to standard regimens in adult patients undergoing RIC HSCT for lymphoma in order to assess the possible benefit of sirolimus on HSCT outcome. 139 patients were randomized. There was no difference overall in 2‐year overall survival, progression‐free survival, relapse, non‐relapse mortality or chronic GVHD. However, the sirolimus‐containing arm had a significantly lower incidence of grade II‐IV acute GVHD (9% vs. 25%, P = 0·015), which was more marked for unrelated donor grafts. In conclusion, the addition of sirolimus for GVHD prophylaxis in RIC HSCT is associated with no increased overall toxicity and a lower risk of acute GVHD, although it does not improve survival; this regimen is an acceptable option for GVHD prevention in RIC HSCT. This trial is registered at clinicaltrials.gov (NCT00928018).     

Polymyositis as a manifestation of chronic graft-versus-host disease

OBJECTIVE: Chronic graft-versus-host disease (GVHD) after haematopoietic stem cell transplantation (HSCT) has similarities to some idiopathic autoimmune diseases, including polymyositis. To investigate the relationship between chronic GVHD and idiopathic myositis we conducted a detailed analysis of all cases of myositis occurring in a large series of HSCT patients. METHODS: We conducted a retrospective chart review of all cases of myositis that developed in 7161 patients who underwent HSCT at the Fred Hutchinson Cancer Research Center between 1969 and 1999. RESULTS: Among 1859 individuals who developed chronic GVHD, 12 developed myositis. No patients developed myositis without chronic GVHD. Myositis was first identified between 7 and 55 months after transplantation. In histopathology, electromyography, laboratory values and response to immunosuppressive therapy, the cases resembled idiopathic polymyositis. Autoantibodies were found in eight cases. CONCLUSIONS: Myositis in the chronic GVHD population occurred with an incidence higher than expected by chance, suggesting that muscle may be a target tissue for chronic GVHD. Recent studies have implicated allogeneic cells persisting after maternal-fetal cell transfer in selected autoimmune diseases, including myositis. This report lends support to the possibility that both idiopathic myositis and chronic GVHD-related myositis could involve allo-autoimmune responses.     

Chronic graft-versus-host disease and late effects after hematopoietic stem cell transplantation

Late effects following HSCT are related to either the transplant process or to the transplant preparative regimen. Problems related to the transplant process include delayed recovery of the immune system and chronic GVHD. Chronic GVHD presents between 3–14 months post-HSCT in approximately 20% of matched sibling transplants and 40% of matched unrelated donor recipients. Most commonly involved sites are skin, mouth, liver, gastrointestinal tract, and eye. Patients with platelet count <100,000/ml and receiving cortocosteroid therapy at day 80 with any clinical manifestations of chronic GVHD require prolonged immune suppressive therapy with prednisone, cyclosporine ±other agents. Treatment should be administered until all clinical and pathological signs and symptoms of chronic GVHD have resolved which may take one to several years. Problems related to the transplant preparative regimen include those involving the endocrine system, eyes, lungs, bone, and development of secondary malignancies. Endocrine deficiencies include growth failure with growth hormone (GH) deficiency, overt hypothyroidism, primary gonadal failure, Type 1 or Type 2 diabetes, and exocrine pancreatic insufficiency. These problems develop at any time post-HSCT, but usually occur within the first few years and should be treated with appropriate hormone supplementation. Eye problems are primarily related to development of cateracts secondary to total body irradiation (TBI) or prolonged corticosteroid use. Cateracts developing after fractionated frequently do not require removal. Pulmonary problems may be due to bronchiolitis obliterans (BO) or to restrictive lung disease. BO may be associated with chronic GVHD and may respond to chronic GVHD therapy. Restrictive lung disease does not occur for many years after HSCT. There is not therapy for this problem. Development of decreased bone mineral density (BMD) is related to GH deficiency and/or corticosteroid therapy. Treatment includes withdrawal of corticosteroids, administration of GH and calcium, Vitamin D and antiresorptive agents. All malignant disease survivors are at risk for development of secondary malignancies including survivors of HSCT. Recipients of TBI are at highest risk as are children. All pediatric and adult survivors of HSCT should be followed for their life-time for development of delayed effects of transplantation.