Second Allogeneic Bone Marrow Transplantation after Myeloablative Conditioning Analysis of 43 Cases from Single Institution

Abstract

Between March 1984 and December 1999, a total of 43 second related allogeneic BMT procedures after myeloablative conditioning were carried out in our institution, 37 following allogeneic, and 6 following autologous BMT. Thirty one patients were males (72%). At 1st BMT (BMT<PRE>1</PRE>), median age was 11.5 years (range, 0.16-45 years). BMT<PRE>1</PRE> was carried out for the diagnosis of AML in 13 patients (30%), SAA in nine (21%), ALL in six (14%), CML in six (14%), immunodeficiency in three (7%), NHL in two, β-thal in two, HD in one, Red cell aplasia in one. HLA matching status for allogeneic BMT<PRE>1</PRE> was full match in 33, one antigen mismatch in two and haplo identical in two patients. Median age at the 2nd BMT (BMT<PRE>2</PRE>) was 14 years (range, 0.41-46.7 years). Indications for BMT<PRE>2</PRE> were recurrent hematologic neoplasm in 23 patients (53%), primary graft failure in 12 (28%) and late graft failure in 8 (19%). Median time from BMT<PRE>1</PRE> to recurrence of hematologic neoplasm or late graft failure was 10 months (range, 2.5- 88 months). Median BMT<PRE>1</PRE> to BMT<PRE>2</PRE> interval was 13 months (range, 1-107 months). For BMT<PRE>2</PRE>, the same donor was used in 29 patients, while 14 patients had alternate related donor (12 full match, 1-one Ag mismatch, 1 haplo identical). A different conditioning regimen was used in the majority of the patients (39, 91%). Radiation containing conditioning regimen were used mostly for patients previously conditioned with chemotherapy only for BMT<PRE>1</PRE> and chemotherapy conditioning±ATG for those who received radiation containing conditioning at BMT<PRE>1</PRE>. Bone marrow was the stem cell source for all patients at BMT<PRE>2</PRE> and all except three autologous peripheral stem cell transplantation patient at BMT<PRE>1</PRE>. Significant organ toxicity leading to procedure related death in 13 patients (30%) was observed after BMT<PRE>2</PRE>. At a median follow up of 36 months after BMT<PRE>2</PRE>, 22 patients (51%) are alive (20 free of disease, 2 with recurrent disease) with overall median survival of 47.5 (SD±9) months. Univariate analysis of relevant clinical factors identified the following variables as the only statistically significant favorable prognostic factors for overall survival: BMT<PRE>1</PRE>-BMT<PRE>2</PRE> interval of ≥6 months (P=0.0007) and age at BMT<PRE>2</PRE> ≤10 years (P=0.041). The nature of underlying disease (neoplastic or non-neoplastic) was not statistically significant (P=0.23). There was no statistically significant difference in survival outcome of BMT<PRE>2</PRE> using same donor vs. alternate related donor (P=0.51). Due to the relatively limited sample size, multivariate analysis was not attempted. This single institution study suggests that second allogeneic BMT after myeloblative conditioning has an acceptable treatment related morbidity/mortality and favorable outcome if performed at age ≤10 years and with an interval of ≥6 months after the first BMT. Additionally same donor can successfully be used for the second transplant with similar survival outcome to alternate donor.

Keywords:

• Second allogeneic bone marrow transplantation
• Graft failure
• Leukemia relapse
• Myeloblative