Page 1414 - Hematology_ Basic Principles and Practice ( PDFDrive )

1260 Part VII Hematologic Malignancies

1992–1999. A study of Cy/TBI in 28 CLL patients observed a because of relapse was 18%. Finally, a British study of 41 CLL
100-day TRM of 11%. Five-year PFS and OS were 78% and 78% patients who received fludarabine, melphalan, and alemtuzumab
for chemosensitive patients compared with 26% and 31% for refrac- followed by an allogeneic SCT from a related (n = 24) or unrelated
tory patients. (n = 17) donor observed a 2-year OS and TRM of 51% and 26%.
A retrospective European Society for Blood and Marrow Trans- Eleven patients (27%) relapsed and received escalated DLIs, but only
plantation (EBMT) study of 135 patients showed 54% 3-year OS three patients had a sustained response to DLI. Five patients (12%)
and 40% 100-day TRM. The International Bone Marrow Transplant died of relapsed disease.
Registry Database (IBMTR) reported similar findings, with 45% Given the approval and outstanding results observed with agents
3-year OS and 30% 100-day TRM in 242 patients. The high TRM that target BCR signaling, the actual timing of transplantation in
may be explained in part by the late stage of the disease in many of CLL has been questioned. Our own practice is to not consider
these patients. Median time from diagnosis to SCT was 41 and 46 reduced intensity allogeneic transplant for CLL in patients unless
months in these two studies, and 37% of patients in the EBMT study they have relapsed after ibrutinib. An exception to this is the younger
were chemorefractory before transplant. In a Canadian study of patient with a complex karyotype receiving ibrutinib where transplant
allogeneic SCT in 30 CLL patients, the 5-year EFS and OS were might be considered as part of consolidation therapy given the high
both 39%, with 48% for patients with sibling donors. The role of risk of eventual relapse. Further follow up on outcome of the kinase
unrelated donor allogeneic SCT was examined by a multicenter study inhibitors will be required before definitive recommendations can be
of 38 patients, 92% of whom received TBI. Five-year PFS and OS made to where transplant should be considered in CLL
were 30% and 33%, and TRM was 38%. Although there are no
prospective randomized studies, a retrospective comparison showed
a 3-year DFS of 57% for allogeneic SCT versus 24% for purged Management of Chronic Lymphocytic Leukemia in
autologous SCT. Finally, allogeneic SCT appears to overcome the Specialized Centers
adverse prognosis associated with an unmutated IGHV; an analysis
of 34 CLL patients who underwent SCT found that only two of 14 Given the recent advent of prognostic markers and treatment options
patients who received allogeneic SCT relapsed, compared with 13 of in CLL, a recent study that examined the impact of physician exper-
20 patients who underwent autologous SCT. Thus, myeloablative tise on patient outcomes in CLL has shown that disease-specific
allogeneic SCT may provide superior DFS to patients with CLL expertise made significant differences in outcomes across all aspects
compared with autologous SCT. Although the 3-year DFS after of patient care from prognostic evaluation to choice of therapy. These
allogeneic SCT is approximately 50%, longer follow up is needed to findings suggest that the expertise of the physician caring for the
determine if the disease remissions are durable. However, this DFS patient with CLL/SLL is an independent prognostic variable that may
advantage is offset by significantly higher TRM, thus limiting the use not be related to the number of patients he or she manages. We
of allogeneic SCT in CLL. Limited data indicate that Bu/Cy may be therefore recommend that all patients with newly diagnosed CLL/
particularly toxic in this population; by contrast, TBI regimens have SLL should be managed in consultation with a CLL expert at a ter-
acceptable TRM. To preserve the immunologic GVL effect while tiary care center with access to the most recent molecular diagnostic
reducing TRM, the focus of clinical SCT practice in CLL has turned tools.
to nonmyeloablative or reduced-intensity allogeneic SCT.
SPECIAL CLINICAL SCENARIOS IN CHRONIC
Nonmyeloablative Allogeneic Stem Cell Therapy LYMPHOCYTIC LEUKEMIA

Young Patients (Younger Than 50 Years of Age) With
Ideally, the goal is to harness the GVL effect of allogeneic SCT for
patients with CLL while reducing TRM from acute graft-versus-host- Chronic Lymphocytic Leukemia
disease (GVHD), acute infection, and organ toxicity associated with
myeloablative conditioning. Fludarabine, busulfan, and ATG were As mentioned previously, CLL is a disease of elderly adults, with only
administered to 30 German CLL patients; the stem cell source was a 10% of patients being younger than the age of 50 years at diagnosis.
matched related (n = 15) or unrelated (n = 15) donor. Grade 2–4 acute Although CLL patients live for a prolonged period of time, young
GVHD was observed in 56% of patients and 75% developed chronic patients without comorbid illnesses have a great potential to have
GVHD. Responses were seen in 93% of patients, with 40% achieving their lives significantly shortened by the disease, irrespective of their
CR. Of note, it took up to 2 years for patients to achieve CR, suggest- cytogenetic abnormalities. In addition, stress associated with job
ing a GVL effect. All patients achieved a molecular CR by PCR, but performance, insurance coverage maintenance, and disease-related
only six patients were in continued molecular CR after a median follow symptoms are most significant in this age group. Special attention to
up of 2 years. Two-year TRM, PFS, and OS were 15%, 67%, and 72%, psychosocial issues related to CLL should occur early during the
respectively. The EBMT retrospectively examined 77 CLL patients course of the disease to allow patients to maintain or resume their
who received a variety of nonmyeloablative conditioning regimens, normal lifestyles as soon as possible. In the absence of impending
followed by allogeneic SCT. The 1-year TRM was 18%, and the 2-year need for therapy, our approach is generally not to empirically pursue
probability of relapse was 31%. Two-year DFS and OS were 56% and HLA typing or examine transplant options before the development
72%, respectively. Nineteen patients received donor lymphocyte infu- of symptomatic disease. When therapy is initiated for this group of
sions (DLIs) for relapse or incomplete donor chimerism, but only seven patients, aggressive intervention to promote prolonged remission
responded to DLI (37%). Unfortunately, this study was complicated duration is always compared with prolonged disease control state
by the heterogeneity of conditioning regimens and the use of ATG or with the use of kinase inhibitors. SCT and/or CAR-T–cell therapy
Campath-1H for T-cell depletion of the grafts in 40% of patients. A is generally considered for patients in this age group who have high-
retrospective analysis of 73 CLL patients who underwent nonmyeloab- risk cytogenetic abnormalities in first remission and for all patients
lative SCT and 82 patients who underwent myeloablative allogeneic who relapse after initial therapy unless high-risk cytogenetic abnor-
SCT showed that the TRM was significantly reduced in the former malities are not present and a CR is attained.
group, with a hazard ratio of 0.4; however, there was no difference in
EFS or OS between the two groups.
Sixty-four patients received 200 cGy of TBI, with (n = 53) or Patients With Fludarabine-Refractory Chronic
without (n = 11) fludarabine followed by an allogeneic SCT from a Lymphocytic Leukemia
related (n = 44) or unrelated (n = 20) donor. The 2-year DFS and
OS were 52% and 60%, respectively, and the 2-year TRM was 22%. Fludarabine-refractory CLL is generally considered to exist if a patient
The incidence of relapse at 2 years was 26%, and the mortality has not responded to a fludarabine-based therapy or relapses within