Bone Marrow Necrosis in Adult Acute Leukemia and Non-Hodgkin's Lymphoma

PURPOSE Low-dose total body irradiation (TBI) is used to treat non-Hodgkin's lymphoma (NHL) and several other malignancies. Large volumes of bone marrow and other tissue receive considerable exposure, but few studies have quantified late carcinogenic sequelae. PATIENTS AND METHODS A cohort of 61 2-year survivors of NHL treated initially with low-dose TBI was monitored for second cancer occurrence. Data on primary and subsequent therapy were collected, and cumulative dose of radiation to active bone marrow (ABM) (median, 5.2 Gy) was reconstructed. RESULTS Thirteen second primary cancers occurred. Four patients developed acute nonlymphocytic leukemia (ANLL), which represents a relative risk (RR) of 117 (95% confidence interval [CI], 31.5 to 300) compared with population rates. A fifth patient was diagnosed with myelodysplastic syndrome (MDS). All five patients with secondary hematologic malignancies subsequently received salvage treatment, with either alkylating agents alone (n = 1) or combined modality therapy (CMT) (n = 4). Overall, eight solid tumors were observed (RR = 2.0; 95% CI, 0.9 to 4.0). The 15-year cumulative risks of all second cancers and secondary ANLL were 37% and 17%, respectively. CONCLUSIONS Despite the small number of subjects, a considerable risk of leukemia was observed among patients treated with low-dose TBI in combination with CMT including alkylating agents. Based on these results, approximately eight to nine excess ANLLs might be expected to occur among 100 NHL patients treated with low-dose TBI and salvage treatment and followed-up for 15 years.

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Outcome in Patients With Myelodysplastic Syndrome After Autologous Bone Marrow Transplantation for Non-Hodgkin's Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.10.3128 ◽

1999 ◽

Vol 17 (10) ◽

pp. 3128-3135 ◽

Cited By ~ 139

Author(s):

Jonathan W. Friedberg ◽

Donna Neuberg ◽

Richard M. Stone ◽

Edwin Alyea ◽

Haddy Jallow ◽

...

Keyword(s):

Bone Marrow ◽

Myelodysplastic Syndrome ◽

Median Survival ◽

Hodgkin’S Lymphoma ◽

Autologous Bone Marrow Transplantation ◽

Autologous Bone Marrow ◽

Hodgkin's Lymphoma ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Autologous Bone

PURPOSE: The absolute risk of myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for non–Hodgkin's lymphoma (NHL) exceeds 5% in several reported series. We report the outcome of a large cohort of patients who developed MDS after ABMT for NHL. PATIENTS AND METHODS: Between December 1982 and December 1997, 552 patients underwent ABMT for NHL, with a uniform ablative regimen of cyclophosphamide and total body irradiation followed by reinfusion of obtained marrow purged with monoclonal antibodies. MDS was strictly defined, using the French-American-British classification system, as requiring bone marrow dysplasia in at least two cell lines, with associated unexplained persistent cytopenias. RESULTS: Forty-one patients developed MDS at a median of 47 months after ABMT. The incidence of MDS was 7.4%, and actuarial incidence at 10 years is 19.8%, without evidence of a plateau. Patients who developed MDS received significantly fewer numbers of cells reinfused per kilogram at ABMT (P = .0003). Karyotypes were performed on bone marrow samples of 33 patients, and 29 patients had either del(7) or complex abnormalities. The median survival from diagnosis of MDS was 9.4 months. The International Prognostic Scoring System for MDS failed to predict outcome in these patients. Thirteen patients underwent allogeneic BMT as treatment for MDS, and all have died of BMT-related complications (11 patients) or relapse (two patients), with a median survival of only 1.8 months. CONCLUSION: Long-term follow-up demonstrates a high incidence of MDS after ABMT for NHL. The prognosis for these patients is uniformly poor, and novel treatment strategies are needed for this fatal disorder.

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Translocation (14;18)-positive cells are present in the circulation of the majority of patients with localized (stage I and II) follicular non- Hodgkin's lymphoma

Blood ◽

10.1182/blood.v82.8.2510.2510 ◽

1993 ◽

Vol 82 (8) ◽

pp. 2510-2516 ◽

Cited By ~ 40

Author(s):

AC Lambrechts ◽

PE Hupkes ◽

LC Dorssers ◽

MB van't Veer

Keyword(s):

Bone Marrow ◽

Lymph Node ◽

Peripheral Blood ◽

Hodgkin’S Lymphoma ◽

Lymph Node Biopsy ◽

Stage I ◽

Hodgkin's Lymphoma ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Sensitive Polymerase Chain Reaction

Abstract Stage I and II follicular non-Hodgkin's lymphoma (NHL) is clinically defined as a localized disease. To study the possibility that this disease is in fact disseminated, we used the sensitive polymerase chain reaction (PCR) method using translocation (14;18) as marker. Samples from 21 patients who were clinically diagnosed with stage I or II follicular NHL were analyzed for the presence of t(14;18)-positive cells using PCR. We analyzed (1) the diagnostic lymph node biopsy and (2) the peripheral blood or bone marrow samples from these patients. Translocation (14;18) cells were detected in the diagnostic lymph node biopsies of 12 patients. In 9 of these patients, t(14;18)-positive cells were detected in peripheral blood and/or bone marrow samples at diagnosis and/or after therapy. Thus, in 75% of the follicular NHL patients carrying the t(14;18) as a marker for lymphoma cells, t(14;18)- positive cells were detected in peripheral blood and bone marrow at diagnosis and after therapy. Our results show that t(14;18)-positive cells can be detected in the circulation of patients with stage I and II follicular NHL, indicating that, although diagnosed as localized, the disease is disseminated.

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