Markedly elevated serum IgE levels following allogeneic and syngeneic bone marrow transplantation

Serum IgE levels were studied in 25 bone marrow transplant recipients (in 12 patients twice weekly and in 13 patients, at random). A 2-748- fold increase in serum IgE was recorded in 20 of the 25 patients after transplantation, the highest IgE value observed being 8,000 kU/liter. The IgE elevation appeared concomitantly with acute graft-versus-host disease (GVHD) in 14 patients. Both events occurred on day 24 +/- 2 (mean +/- SE). When the acute GVHD was diagnosed, there was a significant increase in serum IgE as compared to the first posttransplantation value. In one patient in whom GVHD recurred, a second IgE peak was seen, and in another patient with flaring GVHD, IgE levels increased on several occasions. In 6 patients without clinical signs of GVHD, a rise in IgE occurred on day 35 +/- 12. One of these patients was grafted with marrow from her identical twin. The rise in IgE did not correlate with an elevated proportion of eosinophil granulocytes. In the majority of the patients, no correspondent increases in serum IgG, IgA, or IgM were seen during the period with increased IgE after transplantation.     

Changes in serum erythropoietin levels during allogeneic bone marrow transplantation

Serial serum erythropoietin levels were measured in 10 consecutive patients undergoing allogeneic bone marrow transplantation. Observed erythropoietin levels are compared with those predicted from a large control population of anaemic patients not receiving chemotherapy. There was an initial acute rise in serum erythropoietin, peaking between days 1 and 4 after marrow transfusion, which was unrelated to changes in haemoglobin concentration. Patients maintained serum erythropoietin concentrations at around twice the predicted level for the first 2 weeks following transplantation, with a gradual fall into the expected range by wk 3. Erythropoietin levels did not change with episodes of bacterial infection or acute graft-versus-host disease. A patient with severe aplastic anaemia had initial successful engraftment with normalisation of erythropoietin levels, but showed a marked and amplified rise in erythropoietin 2 wk before falling peripheral blood counts indicated failure of the bone marrow graft.     

Serum immunoglobulin levels following allogeneic bone marrow transplantation

Summary In order to study the posttransplant evolution of serum immunoglobulin levels, we measured serum IgG, IgA and IgM levels in 50 recipients of allogeneic bone marrow before transplantation and at different intervals thereafter (days 39, 120, 365 and 730). IgG and IgM levels were depressed for 1 year and IgA levels for 2 years posttransplant. Immunoglobulin deficiency was more severe and prolonged in patients with graft versus-host-disease. Hypogammaglobulinemia may contribute to the frequent infections observed in these patients, especially those with chronic graft-versus-host disease.     

Successful pregnancy following allogeneic bone marrow transplantation after conditioning by thoraco-abdominal irradiation

A 26-year-old woman delivered a normal child 5 years after bone marrow transplantation for severe aplastic anemia. The conditioning regimen comprised high dose cyclophosphamide and thoraco-abdominal irradiation (6 Gy). This and two previous cases demonstrate that normal pregnancy can follow total body or thoracoabdominal irradiation.     

Hyperammonemia following allogeneic bone marrow transplantation

Hyperammonemia is a rare and serious complication of intensive cytotoxic chemotherapy. We report the case of a patient who developed profound idiopathic hyperammonemia following bone marrow transplantation for chronic myelogenous leukemia. Despite rapid institution of hemodialysis, sodium benzoate, and the experimental agent sodium phenylacetate, the patient ultimately succumbed to complications of this metabolic derangement. The literature is reviewed, and recommendations for an approach to this complication of marrow transplantation are proposed.     

Autoimmune pancytopenia following allogeneic bone marrow transplantation

A 47-year-old female developed autoimmune hemolytic anemia, autoimmune neutropenia, and autoimmune thrombocytopenia 19 months following allogeneic bone marrow transplantation for chronic myelogenous leukemia. Treatment with high-dose corticosteroids resulted in marked improvement in all three cell lines.     

Systemic nocardiosis following allogeneic bone marrow transplantation

Abstract: Five cases of systemic Nocardia infection were diagnosed among 301 allogeneic bone marrow transplant recipients. A sixth case included in this report received her transplant at another institution. The cumulative annual incidence rate of this infection was 1.75%. All patients had been treated previously for acute graft-versus-host disease (GVHD). At the time of diagnosis of systemic Nocardia infection, a median of 198 (range 148–1121) days after transplantation, all patients had extensive chronic GVHD and were taking 2 to 3 immunosuppressive medications. Prior to diagnosis of Nocardia infection patients had experienced multiple opportunistic infections, including infections with Mycobacterium avium-intracellulare, Pneumocystis carinii , and cytomegalovirus antigenemia. Treatment with trimethoprim-sulfamethoxazole (TMP-SMX), ceftriaxone, or carbapenem antibiotics resulted in a median survival of 219 days from the time of diagnosis and an actuarial 1-year survival of 40%. All patients who received more than 2 weeks of therapy were cured of their infections. Notably, 5/6 patients in this cohort were unable to take TMP-SMX because of myelosuppression. In comparison with randomly selected control patients, the use of pentamidine for prevention of P. carinii infection was associated with a marginal increase in the risk of Nocardia infection. We postulate that the use of TMP-SMX may be of benefit in the prophylaxis of infections other than P. carinii in patients with chronic GVHD.     

Gynecological abnormalities following allogeneic bone marrow transplantation

Forty-four post-pubertal women were studied 261-4628 days after allogeneic transplantation to determine the nature and degree of gynecological abnormalities following bone marrow transplantation. Evaluations included pelvic examinations, exfoliative cytology, serum gonadotropin levels, direct preparations for micro-organisms, and microbial cultures. Pelvic abnormalities were detected in 35 of 44 (80%) women and resembled atrophic changes known to occur after ovarian failure. Findings included reduced vaginal elasticity and rugal folds, pale tissues, small vaginal, uterine and cervical size, atrophic vulvovaginitis, introital stenosis, and loss of pubic hair. Atrophic abnormalities were noted in 33 of 36 recipients of total body irradiation (TBI) compared to two of eight women not prepared with TBI (p = 0.02). Vasomotor symptoms were reported in 67% of TBI recipients compared to 38% of those not given TBI. Elevated serum gonadotropin levels suggested that TBI had caused the ovarian failure. Recognition of these gynecological abnormalities can lead to earlier hormone replacement, alleviating unnecessary discomfort and improving the well-being of the marrow transplant recipient.     

Homogeneous immunoglobulins following allogeneic bone marrow transplantation

Homogeneous immunoglobulins are frequently detected in the serum of patients undergoing allogeneic bone marrow transplantation (BMT). The aim of the present study was to further characterize the incidence of this phenomenon and its correlations with laboratory and clinical data. Serum samples were gathered from 29 patients undergoing allogeneic or syngeneic BMT for chronic myeloid leukemia (CML), and serial protein (IgG, IgA and IgM) quantification, electrophoresis and immunofixation were performed. Transient mono- or oligoclonal gammopathies were observed in 23 out of 29 patients between days 20 and 1,750 following transplantation. The presence of homogeneous immunoglobulins was not correlated with the following clinical parameters: graft-versus-host disease, bacterial sepsis, Epstein-Barr virus or cytomegalovirus infection or invasive fungal infection. Therefore, the development of mono- or oligoclonal immunoglobulins may represent a complex disorder of B cell regeneration which may be caused by an intrinsic B cell defect, or a failure in the regenerating T cell system, or both, manifesting itself in a restricted antibody diversity after allogeneic BMT.     

HTLV-I-associated myelopathy following allogeneic bone marrow transplantation.

A 39-year-old polytransfused patient with aplastic anemia acquired transfusion-associated HTLV-I infection shortly before transplantation. The patient underwent allogeneic bone marrow transplantation and developed HTLV-I associated myelopathy 3 years later. Clinical abnormalities and a host of atypical findings are presented in the context of previous reports describing uncommon features of the disease.     

Thrombotic microangiopathy following allogeneic bone marrow transplantation.

Thrombotic microangiopathy is one of the complications of bone marrow transplantation and is related to other complications such as graft-versus-host disease, veno-occlusive disease, diffuse alveolar hemorrhage, and cytomegalovirus infection. Thrombotic microangiopathy occurred in three out of 12 patients who underwent allogeneic bone marrow transplantation over the past 1 year at our department. We compared the changes in cytokines and other molecules between patients with and without microangiopathy from before conditioning to the early post-transplantation period. All three patients with microangiopathy showed a significant increase of interleukin-12 at the time of leukocyte recovery after transplantation (two-way layout analysis of variance; P < 0.05), while none of the patients without microangiopathy showed an increase of interleukin-12. No significant differences were found between the two groups with respect to the other cytokines and molecules that were tested. These findings suggested that thrombotic microangiopathy might be predicted at an early stage after bone marrow transplantation by detecting an increase of interleukin-12 at the time of leukocyte recovery. The possibility that thrombotic microangiopathy is related to inflammation or autoimmunity was also suggested.     

Idiopathic hyperammonemia following allogeneic bone marrow transplantation for refractory lymphoma

Idiopathic hyperammonemia (IHA) is a rare but serious complication of stem cell transplantation. We report a patient with immunoblastic lymphoadenopathy-like T-cell lymphoma who developed IHA 10 days after allogeneic bone marrow transplantation from an HLA-matched unrelated donor. Despite intensive supportive care, the patient died due to this metabolic disorder two days later. Being mindful of the possibility of IHA in patients who develop confusion and respiratory alkalosis soon after stem cell transplantation would allow earlier treatment and might improve the chance of survival.     

Circulating erythropoietin levels after bone marrow transplantation: inappropriate response to anemia in allogeneic transplants.

We studied 24 recipients of autologous bone marrow transplantation (ABMT) or allogeneic BMT (BMT) to determine whether impaired erythropoietin (Epo) response to anemia could delay full erythropoietic recovery. Observed Epo levels were compared with predicted levels based on the relationship between Epo and hematocrit in 125 control subjects. Circulating Epo levels were normal during conditioning and the early posttransplant period. Between days 21 and 180, Epo levels remained normal in ABMT patients but were inappropriately low for the degree of anemia in BMT patients. Median time to full erythropoietic engraftment was longer in BMT than in ABMT recipients. Circulating Epo returned to appropriate levels after day 180, except in patients with active cytomegalovirus infection. We conclude that impaired Epo response to anemia can contribute to delayed erythropoietic recovery after allogenic BMT. Renal toxicity of ciclosporin, interaction between host and donor marrow, and cytomegalovirus infection might play a role. This study could support the use of recombinant human Epo to accelerate erythropoietic engraftment after BMT.     

Lymphocyte subset reconstitution following human allogeneic bone marrow transplantation

We analysed the reconstitution of lymphocyte subset during the first 4 weeks after human allogeneic bone marrow transplantation (BMT) in relation to the recovery of hematopoiesis. Lymphocyte subset analysis was performed with flow cytometry. We performed allogeneic BMT from HLA matched sibling donor in 9 patients. We analysed the positive percentage of each surface antigen and analysed data prior to conditioning therapy and weekly during the first 4 weeks after BMT. Results were as follows: Two or 3 weeks after BMT, percentages of CD8+ (CD8+ CD11b+) lymphocyte and CD16+ (CD16+ CD57-) lymphocyte (NK cell) were increased, and those of CD3+ lymphocyte and CD4+ (CD4+ Leu8+) lymphocyte decreased. And the ratio of CD4+ lymphocytes to CD8+ lymphocytes decreased below 1.0 at 2 or 3 weeks after BMT and remained low. In relation to the recovery of hematopoiesis, CD16+ lymphocyte (especially CD16+ CD57- lymphocyte) percentages at the third weeks correlated significantly to the recovery of granulocyte, reticulocyte, and platelet. It seems that CD16+ lymphocytes may play a role in bone marrow cell engraftment and the recovery of hematopoiesis.     

Treatment of solid tumors following allogeneic bone marrow transplantation

Second solid tumors are well known late complications after bone marrow transplantation. Treatment strategies are ill defined. We retrospectively evaluated treatment and outcome in a single institution. From August 1974 to July 1996, six solid tumors were observed in five of 387 patients 2 to 13 years after BMT, corresponding to a probability of developing a second solid tumor of 9% (1-17%, 95 CI) at 15 years: these comprised endometrial carcinoma, carcinoma of the thyroid gland, cervical carcinoma, sarcoma of the small intestine, osteosarcoma of the tibia and ovarian carcinoma. All five patients were treated as intensively as they would be without a history of BMT. At last follow-up four of the five patients were alive and without signs of tumor. We postulate that second solid tumors after BMT should be treated as de novo tumors. Early detection based on consequent clinical follow-up of the transplant patients might explain the relatively good outcome.     

Thyroid and pituitary function following allogeneic bone marrow transplantation

Thyroid function was evaluated in 13 consecutive patients with chronic myelogenous leukemia to verify in allogeneic bone marrow transplantation if the fractionated irradiation protocol with low dose rate, previously applied to reduce the damage to various organs, also prevents the 43% incidence of primary hypothyroidism that occurs after the administration of single dose with higher dose rate. Following bone marrow transplantation, decreased plasma levels of total thyroxine and triiodothyronine and impaired response of thyrotropic cells to thyrotropin-releasing hormone were observed. These alterations reverted to normal in nine months and none of the patients was hypothyroid at the end of follow-up. The damage to thyrotropic cells appears to be selective because the secretion of prolactin was not impaired and that of gonadotropins even increased, as a consequence of gonadal failure. Longer follow-up is needed to determine if this irradiation protocol, which prevents the complication of permanent primary hypothyroidism and does not cause any destruction of thyroid cells, may increase the risk of irradiation-related thyroid tumors.     

Hepatitis B serological changes following allogeneic bone marrow transplantation

Hepatitis B (HBV) reverse seroconversion (RS) in immunocompromised patients with serological evidence of past HBV infection (hepatitis B surface antigen [sAg] negative, core antibody [cAb] positive) has been reported with increasing frequency following allogeneic hematopoietic stem cell transplant (allo‐HSCT). We performed a retrospective review of serial HBV serological testing in patients who had undergone allo‐HSCT at our center between 2000 and 2006. We identified 12 patients with serological evidence of past HBV, including 1 case of RS. Although 7 of these 12 patients had no changes in serological markers detected after transplantation, 5 of them had declining levels of hepatitis B surface antibodies [sAb], with 2 to < 10 IU/mL. The remaining 4 patients with past HBV had loss of antiHBcAb. An additional 14 patients developed isolated antiHBcAb post allo‐HSCT in the setting of receiving HBV screened (HBsAg, antiHBcAb) negative donor stem cells. Monitoring of HBV serological markers (including antiHBsAb) and HBV DNA levels pre allo‐HSCT in recipients and donors, and post allo‐SCT in recipients, would allow early detection and treatment of RS and identify new acquisition of HBV.