Transition from active to palliative care EBMT, Geneva, 03.04.2012 Dr. med. Gayathri Nair Division of Hematology
3 cases of patients who underwent an allogeneic stem cell transplantation in curative intent all 3 relapsed in those 3 cases we opted for different strategies due to numerous reasons
Case 1
Case 1 47 year old male patient married, one daughter diagnosed with multiple myeloma in August 2010 Salmon and Durie III, ISS stadium I multiple bone lesions chemotherapy was started 3 cycles of bortezomib/dexamethason 4 cycles of lenalidomid/dexamethason
Case 1 04/2011 high dose chemotherapy with melphalan followed by autologous stem cell transplantation 06/2011 extramedullary relapse with pulmonary manifestations, multiple enlarged lymph nodes and a supravesical lesion 3 cycles VDT-PACE -> stringent complete remission
Varettoni M, Ann Oncol. 2010 Feb;21(2):325-30
Case 1 11/2011 allogeneic unrelated stem cell transplantation after reduced conditioning regimen engraftment on day +11 on day +28 patient complained of abdominal pain CT/PET scan: multiple lesions/masses in the chest wall and abdomen, multiple affected lymph nodes puncture of one of these lesion confirmed the extramedullary relapse of the multiple myeloma
Case 1 very early timepoint of relapse no treatment options in curative intent -> palliative situation patient wanted further chemotherapies long discussions
Case 1 immunosuppressive therapy was reduced palliative chemotherapy with thalidomide and bortezomib was started clinical condition detoriated further patient died 58 days after allogeneic stem cell transplantation
Case 2
Case 2 48 year old female married, two children 05/2008 first diagnosed with AML (FAB M2, WHO 2008 NOS) 3 cycles of chemotherapy complete remission 02/09 first relapse after the first cylce of chemotherapy no response 2nd cycle of chemotherapy->complete remission
Case 2 06/2009 allogeneic unrelated stem cell transplantation after myeloablative conditioning 09/2009 acute intestinal GVHD requiring immunosuppressive therapy 01/2010 second relapse of AML 1 cycle of chemotherapy starting on 01/2010 DLI 16.03.2010 patient developed severe acute GVHD of the skin and intestinal GVHD immunosuppressive therapy was reinitiated
Case 2 01/2011 third relapse of AML with bone marrow infiltration and myeloid sarcoma of the nose radiation of the myeloid sarcoma immunosuppression was stopped -> complete remission patient developed severe GVHD of the skin (grade IV) escalation of immunosuppressive therapy
Case 2 the further course of the patient was affected by severe chronic GVHD pulmonary GVHD breathing was additionaly impaired due to damage of the mucosa of the nose after radiation intestinal GVHD weight loss (height 165 cm, weight 42 kg, BMI 15.4 kg/m 2 ) GVHD of the skin hyperpigmentation, scarring
Case 2 allogeneic lymphocytes produce a strong graftversus-leukemia effect, but the beneficial effect is limited by graft-versus-host disease in patients with chronic GVHD the reduced relapse rate is associated with a survival benefit Kolb HJ; Blood. 2008 Dec 1;112(12):4371-83 Weiden PL; N Engl J Med. 1979 May 10;300(19):1068-73
Case 2 success story patient is still in complete remission quality of life severly impaired due to chronic GVHD inspite of complete remission palliative situation due to the comorbidites associated with chronic GVHD at which timepoint did the situation switch from active to palliative treatment?
Case 3
Case 3 18 year old male patient only child, apprenticeship as an electrician 03/2010 first diagnosed with AML NOS risk profile: poor risk 3 2 cycles of induction chemotherapy in remission after the first cycle of chemotherapy search for an unrelated donor was ongoing
Case 3 consolidation chemotherapy allogeneic unrelated stem cell transplantation after myeloablative conditioning in August 2010 uncomplicated further course 3 months after transplantation complete morphological and cytogenetical remission
Case 3 no GVHD, immunosuppressive therapy could be stopped 4 months after transplantation routine bone marrow examination 6 months after transplantation -> Relapse
LFS according to the interval between first BM transplantation and relapse Bosi A et al; J Clin Oncol. 2001 Aug 15;19(16):3675-8
Eapen M et al; Bone Marrow Transplant. 2004 Oct;34(8):721-7
Case 3 reinduction chemotherapy (S-HAI) bleeding complications due to DIC no relevant infections during reinduction on day +17 bone marrow examination was performed 90% blast infiltration -> persistent leucemia
Case 3 treatment options 1. upfront transplantation due high tumour load not possible 2. further chemotherapy if a CR can be achieved or the tumour burden can be considerably reduced, then proceed to a 2nd transplant 3. palliative care
OS according to status at second transplant Bosi A et al; J Clin Oncol. 2001 Aug 15;19(16):3675-8
Case 3 patient opted for a palliative therapy he argued that he did not want to undergo further treatment knowing that the chances of a durable remission were very low he wanted to go home and enjoy life
Case 3 patient was in a very good clinical condition in aplasia requiring platelet and blood transfusion 2x/week regular substitution of fibrinogen due to persistent DIC with epistaxis 3 months later the patient was admitted to hospital due to pain and fever he denied any life-extending measures and died a few days later in the presence of his family&friends
1. case: patient wanted more, we did not have anything more to offer 2. case: we did whatever was possible remission as main goal was achieved, but quality of life severly impaired goal really achieved? 3. case we wanted to go for a second transplant patient was not willing
Thank you for your attention