Second Malignancies after Allogeneic Hematopoietic Cell Transplantation

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) may prolong life and cure patients suffering from otherwise fatal diseases. However, the growing population of long-term survivors has led to the realization of multiple long-term complications, including the risk of second malignancies. Compared to the autologous setting, allo-HCT carries a much higher risk of posttransplant lymphoproliferative disorder (PTLD), which usually occurs within the first year after allo-HCT and is strongly associated with the Epstein-Barr virus (EBV). Treatment-related myelodysplastic syndromes (tMDS) and second leukemias are extremely rare. Both autologous and allo-HCT carry increased risks for second solid malignancies (SSM). The cumulative incidence of SSM continues to increase in each of the largest studies with as much as 20 years of follow-up, likely related to the long latency of radiation-related SSM. Systematic, prospective monitoring, vigilant screening processes, and well-maintained survivorship clinics and databases are absolute necessities, and should be included in the infrastructure of individual transplant centers and networks, with mandatory periodic reporting of second malignancy incidences. Primary care and transplant physicians alike must be aware of the risk of second malignancies after allo-HCT. Most importantly, guidelines should be developed in regard to screening and prevention of second malignancies, so that physicians can provide state-of-the-art counsel and care for the benefit of our patients.

Therapy-related myelodysplastic syndrome after allogeneic BMT: successful treatment by donor lymphocyte infusions

“…RHG ¼ reverse banding using heat and Giemsa. 45,XY,t(2;21)(q12;q22),À7,del(8)(p21), add(13)(q33),del(20)(q12q13) [5]. t(2;21) was confirmed using WCP21 probe (Kreatech, Strasbourg, France) (data not shown).…”

“…4 In contrast to what has been reported for auto-BMT, t-MDS/AML of recipient origin is a very rare occurrence after allogeneic BMT; among more than 8000 transplanted patients, only 6 cases have been reported in large retrospective studies evaluating long-term complications after allogeneic BMT. 5 In the allogeneic setting, recipient haematopoietic destruction is achieved not only through the conditioning regimen but also with the assistance of the donor immune system, resulting most likely in risk reduction for the recipient. Nevertheless, t-MDS/AML frequency may be higher in transplants with a higher frequency of recipient stem cell survival, as seen with reduced-intensity conditioning transplant.…”

“…The karyotype did not show the typical abnormalities found at diagnosis in leukaemia; however, the karyotype was complex, with three clones involving chromosome 7, as follows (see Figure 1): 46,XY,t(1;15)(p36;q21),del(7) (q31q35),t(12;16)(q21;p12) [5]/45,XY,t(2;21)(q12;q22),À7, del(8)(p21),add(13)(q33),del(20)(q12q13) [5]/45,XY,add(3) (q24),7,10,add(19)(q13), þ mar [3]/ 46,XY [9].…”

“…The karyotype was hyperdiploid (55,XY, þ X, þ 4, þ 6, þ 14, þ 17, þ 18, þ 21x2, þ mar [5]/46, XY [15]). He was enrolled in the multicentric GRAALL 2003 trial and received induction therapy combining VCR, DNR, CY, L-asparaginase, prednisone and intrathecal chemotherapy.…”

Therapy-related myelodysplastic syndrome of recipient origin in a juvenile myelomonocytic leukemia patient 17 years after allogeneic BMT

“…1 Five cases, including the present case, have been described in detail (Table 2). 2,3,4,5 These five cases were characterized by hematological malignancy at primary diagnosis, administration of high-dose TBI at BMT, and complex karyotypes, particularly with other complex abnormal clones at the diagnosis of t-MDS in four cases (patient no.…”