Relapse Risk after Nonmyeloablative Hematopoietic Cell Transplantation for Malignant Diseases.
Authors: Kahl Christoph , Storer Barry , Mielcarek Marco , Maris Mike , Sandmaier Brenda , Maloney David , Chauncey Thomas , Niederwieser Dietger , McSweeney Peter , Bruno Benedetto , Blume Karl , Wade James , Leis Jose , Langston Emilia , Pulsipher Michael , Agura Edward , Storb Rainer 
Published: April 2020

Nonmyeloablative hematopoietic cell transplantation (NMHCT) has become an immunotherapeutic option for patients with a variety of malignant diseases. The susceptibility to malignancy-eradicating graft-versus-tumor effects, however, appears to depend on type and stage of the underlying diseases. Thus, the aim of this study was to estimate relapse risk after NMHCT according to pretransplant disease characteristics.

Between 1997 and 2004, 595 consecutive patients (median age, 55; range, 5–74 years) received related (n=383) or unrelated (n=212) grafts after preparation with total body irradiation (TBI, 200 cGy, n=168) alone, or in combination with fludarabine (90 mg/m2, n=423). The relapse rate per person year (PY) at risk, which corrected for variation in follow-up time and the competing risk of non-relapse mortality, was calculated for 27 different disease and stage categories. No corrections were made for graft rejections, all of which resulted in relapse.

The overall relapse rate per PY was 0.37. As shown in Table 1, patients with chronic lymphocytic leukemia, low-grade Non-Hodgkin lymphoma (NHL) and multiple myeloma had the lowest relapse rates per PY (0.00, 0.09, 0.09; “low-risk”). In contrast, patients with advanced myeloid diseases had a relapse risk per PY of &gt;0.50 (“high-risk”). The increased incidence of graft rejection among patients with chronic myeloid leukemia and myelodysplastic syndrome, however, may have contributed to the higher relapse risk observed in this group. Patients with lymphoproliferative diseases not in remission (Hodgkin disease and high-grade NHL excluded), and myeloid malignancies in remission at transplant had relapse rates per PY of 0.20 – 0.50 (“standard-risk”). For patients deemed at “high risk” for relapse after NMHCT, intensification of the preparative regimens, and/or cytoreductive strategies before or after transplant need to be considered in the design of future transplant protocols.

Relapse Risk Categories Low Risk (n) Relapse Rates per PY Standard Risk (n) Relapse Rates per PY High Risk (n) Relapse Rates per PY CLL, chronic lymphocytic leukemia; MM, multiple myeloma; MDS, myelodysplastic syndrome; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; ALL acute lymphocytic leukemia; CMML, chronic myelomonocytic leukemia; CR, complete remission; CP/AP/BP, chronic-/accelerated-/blast-phase. CLL, CR (4) 0.00 Waldenstrom′s (7) 0.23 high-grade NHL, no CR (18) 0.61 MM, CR (23) 0.09 MM, no CR (109) 0.26 Hodgkin, CR (7) 0.67 low-grade NHL, CR (22) 0.09 CLL, no CR (52) 0.28 Hodgkin, no CR (26) 0.83 low-grade NHL, no CR (49) 0.19 Myelofibrosis (5) 0.28 MDS (RAEB/RAEB-t, 16) 0.51 MDS (RA/RARS, 18) 0.29 MDS, previous chemo (17) 0.65 AML &gt; CR1 (31) 0.30 AML, no CR (10) 0.69 High-grade NHL, CR (16) 0.31 AML, antecedent MDS (31) 0.94 CML, CP1 (27) 0.34 CMML (7) 0.74 AML, CR1 (43) 0.42 CML, CP2 (7) 1.05 ALL, CR1 (9) 0.45 CML, AP/BP (11) 1.05 ALL, &gt; CR1 (7) 0.88 ALL, no CR (4) 1.08