Long-term follow-up of allogeneic bone marrow transplantation for patients with chronic phase chronic myeloid leukemia prepared with a regimen consisting of cyclophosphamide, cytarabine and single-dose total body irradiation conditioning.

We evaluated long-term toxicities and outcomes in 96 patients with chronic phase chronic myeloid leukemia treated with a single bone marrow allograft regimen. Conditioning was cytosine arabinoside, cyclophosphamide (120 mg/kg) and single fraction total body irradiation (500 cGy). Median follow-up was 12.8 years (0.4-19.9 years). Graft failure occurred in one patient, nonfatal veno-occlusive disease in 13 patients (14%). Overall incidences of acute (a) and chronic (c) graft-vs-host disease (GVHD) were 77 and 63%. The 100-day and 1-year transplant-related mortality (TRM) were 1 and 9.2%, respectively, with no change through 5 years. Five- and 10-year event-free survival rates were 56 and 49%, overall survival (OS) rates 72 and 70%, respectively. Forty patients have relapsed: 8 cytogenetic (20%), 10 hematologic (25%) and 22 molecular (55%). Most have been salvaged with donor-leukocyte infusion, second transplants and/or imatinib therapy. Survival was worse for patients transplanted >2 years from diagnosis (10-year OS 56 vs 78%, P=0.01), for patients over 50 years old (10-year OS 44 vs 75%, P=0.05) and for patients without cGVHD (10-year OS 53 vs 86%, P<0.001). This regimen resulted in successful engraftment, low risk of TRM and long-term survival. In an era when imatinib is first line therapy, this regimen offers a potentially low-toxicity, highly successful alternative in the event of poor imatinib response.

Quality of life following bone marrow transplantation: a comparison of patient reports with population norms.

All surviving patients who had received an allogeneic bone marrow transplant at the Princess Margaret Hospital were asked to participate in a health-related quality of life (HQL) study using the Medical Outcomes Survey-Short Form 36 (MOS SF-36), the Satisfaction with Life Domains Scale-Bone Marrow Transplantation (SLDS-BMT) and a current symptoms checklist. The main objective was to compare the health status of BMT survivors with age-adjusted population norms. Of the 251 patients contacted, 93% returned questionnaires. The median follow-up after BMT was 40 months, ranging from 1-253 months. On average, survivors had some diminished HQL relative to the health status of the population in general. Time since transplant had a significant influence on HQL; those less than 3 years from transplant experienced considerable impairment while those who had survived beyond this point were indistinguishable from the normal population in most domains and significantly better in certain psychosocial aspects of health. Many patients still reported symptoms months after BMT; some were mildly affected while others experienced more troublesome symptoms. However, 81% of patients were satisfied with the HQL outcome that they had achieved and 94% would recommend a transplant for someone in similar circumstances.

Detection of donor cell derived acute myelogenous leukaemia in a patient transplanted for chronic myelogenous leukaemia using fluorescence in situ hybridization.

The recurrence of leukaemia following allogeneic bone marrow transplantation appears to develop rarely in donor cells. However, the standard method for assigning the origin of recurrence, metaphase analysis, can be unreliable. We have applied the technique of fluorescence in situ hybridization (FISH) directly on archival Wright stained bone marrow slides obtained from a patient who developed acute myelogenous leukaemia (AML) following allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukaemia (CML). Using a chromosome-specific DNA probe we linked a chromosomal aberration, previously detected by conventional metaphase analysis, directly to morphologically identifiable blast cells. In this way we were able to assess cell-lineage involvement of the secondary leukaemia and assign a donor origin.

Secondary malignancies after bone marrow transplantation in adults.

PURPOSE: The records of 557 consecutive adult recipients of allogeneic-related and -unrelated and syngeneic bone marrow transplants (BMTs) were reviewed to determine the incidence of secondary cancers. PATIENTS AND METHODS: Four hundred fifty-six patients were transplanted for acute lymphocytic leukemia (ALL; n = 79), acute myelogenous leukemia (AML; n = 182), and chronic myelogenous leukemia (CML; n = 195); 42 patients were transplanted for aplastic anemia (AA) and 59 for a variety of other hematologic and nonhematologic disorders, malignant and nonmalignant. Conditioning regimens included high-dose chemotherapy with or without total-body irradiation (TBI). Statistical analyses determined the cumulative incidence of developing a secondary cancer and elucidated the associated risk factors. Complete records (1 to 24 years of follow-up) on all patients were available. RESULTS: Nine patients developed 10 secondary cancers for a cumulative actuarial risk of 12% (95% confidence interval [CI], 4.3 to 23.0) 11 years after transplant. The age-adjusted incidence of secondary cancer was 4.2 times higher than that of primary cancer in the general population. Eight of the 10 were epithelial in origin and three were cutaneous. TBI and acute graft-versus-host disease (GVHD) with a severity > or = grade II were associated with the development of any secondary cancer. On the other hand, chronic GVHD was a risk factor only for the development of secondary skin neoplasms. CONCLUSION: Adult recipients of BMT face a significant risk of developing a secondary malignancy. Their risk is similar to that of other patients with hematologic malignancies who are treated with chemoradiotherapy only. Epithelial tumors, rather than the more commonly reported Epstein-Barr virus (EBV)-associated lymphomas, were most common. The fact that we did not routinely use T-cell-depleted marrow grafts nor anti-T-cell immunoglobulin for the treatment of acute GVHD may explain this variance.

Pneumatosis intestinalis with free air mimicking intestinal perforation in a bone marrow transplant patient.

A case of pneumatosis intestinalis with perforation is reported in a patient after bone marrow allograft for chronic myeloid leukemia. Risk factors included the transplant, prolonged immunosuppression and neutropenia, graft-versus-host disease, extended use of corticosteroids, infection and lower gastrointestinal endoscopic biopsy. The literature is reviewed and a management plan for patients presenting with this complication is discussed.