Neutrophil Recovery
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Blood is Made in the Bone Marrow Neutrophil Recovery: The First Step in Posttransplant Recovery White cells B Lymphocyte Blood Stem Cell Pre-B T Lymphocyte Neutrophils CFUGEMM BFU-E No conflicts of interest to disclose Red cells CFU-E Platelets Mega Bone marrow Blood BAS05_3.ppt Bus11_1.ppt Goals of Blood and Marrow Transplantation Blood and Marrow Transplantation Radiation/Chemotherapy to kill the cancer Replace blood stem cells destroyed by disease or drugs used to treat disease Suppo t until Support u t recovery Rx Destroy malignancy BM High-dose chemotherapy/ radiation (which also destroys blood stem cells) Stem cells to restore marrow & immune defense Immune effects of donor cells BAS05_7.ppt Transplantation of Stem Cells Allows Us to Increase the Dose Intensity of our Treatments Non-hematologic toxicity Need Stem cells Need growth factors Marrow suppression Patient as donor: Autologous Collect & freeze cells Radiation/ Chemo to kill the cancer BM/PB Rx Support until recovery Stem cells to restore marrow & immune defense 1 Healthy Donor: Allogeneic Graft Conditioning may or may not kill cancer cells Competing Risks Acute and/or chronic GvHD Viral infections CMV, VZV, PCP, IP Complications: Bacterial infections HSV mucositis PBSC/BM harvests in ABMT Blood & Marrow Changes: BM/PB Rx Secondary tumors, cataracts, endocrine changes, QoL VOD Marrow function Collect & freeze Support until recovery BMT Process: Immune function BM/SC re-infusion gcsf eg: DHAP and GF and PBSC Donor search or obtain autologous stem cells Red cell transfusions Platelet transfusions Chemo XRT Growth factors Supportive Therapy: Stem cells to restore marrow & immune defense, destroy cancer cells Antiemetics Nutrition Antibiotics TIME LINE Disease State: -12 -4 -2 Primary diagnosis and treatment Relapse and salvage therapy 0 High-dose myeloablative therapy 1 2 6 Marrow failure Disease remission Disease recurrence 60 months Continuous complete remission (cure) SCS06_43.ppt Barriers to Transplant Success Blood is Made in the Bone Marrow White cells B Lymphocyte Blood Stem Cell Pre-B T Lymphocyte Neutrophils CFUGEMM BFU-E Red cells CFU-E Platelets Regimen toxicity Hematopoietic recovery/ Engraftment GVHD Relapse Mega Bone marrow Blood BAS05_3.ppt Complications of Prolonged Neutropenia Maturation of Neutrophils Infection Infection . . . . . Infection Risk of infection increases dramatically when: Neutrophils are < 500/mm3 Neutropenia persists for >10 days Also, when occurs after conditioning, usually accompanied by lack of recovery of all other blood cells Appearance of bands and segs the earliest dependable sign of marrow regeneration – key milestone in posttransplant recovery 2 Absolute Neutrophil Count What Number of bands+segs per mm3 (% bands + % segs) x WBC/mm3 When First of three consecutive measurements >500/mm3 AFTER an initial decline POST-TED INITIAL ANC RECOVERY Was ≥0.5 x 109/L achieved for 3 consecutive labs? ** Yes, first date of 3 labs: ___ ___ ___ ___ - ___ ___ - ___ ___ YYYY MM DD No, ** No last assessment: ___ ___ ___ ___ - ___ ___ - ___ ___ YYYY MM DD ** Never below Previously reported Unknown Did graft failure occur? Yes No Form 2100 Form 2100 Is (was) there evidence of hematopoietic recovery following the initial HSCT? (check only one) 1 Yes, ANC ≥ 500/mm3 achieved and sustained for 3 lab values with no subsequent decline (date) 2 Yes, ANC ≥ 500/mm3 for 3 lab values with subsequent decline in ANC to < 500/mm3 for ≥ 3 days (dates) 3 No, ANC ≥ 500/mm3 was not achieved and there was no evidence of recurrent disease in the bone marrow 4 No, ANC ≥500/mm3 was not achieved and there was documented persistent disease in the bone marrow postHSCT 5 ANC never dropped below 500/mm3 at any time after the start of the preparative regimen Is (was) there evidence of hematopoietic recovery following the initial HSCT? (check only one) 1 Yes, ANC ≥ 500/mm3 achieved and sustained for 3 lab values with no subsequent decline (date) 2 Yes, ANC ≥ 500/mm3 for 3 lab values with subsequent decline in ANC to < 500/mm3 for ≥ 3 days (dates) 3 No, ANC ≥ 500/mm3 was not achieved and there was no evidence of recurrent disease in the bone marrow 4 No, ANC ≥500/mm3 was not achieved and there was documented persistent disease in the bone marrow postHSCT 5 ANC never dropped below 500/mm3 at any time after the start of the preparative regimen What Declines Are We interested In? Form 2100 Declines that compromise patient wellbeing and/or require intervention Not the “wiggling” around the 500 level that can occur in the early posttransplant period Consider the inherent error of the test Is (was) there evidence of hematopoietic recovery following the initial HSCT? (check only one) 1 Yes, ANC ≥ 500/mm3 achieved and sustained for 3 lab values with no subsequent decline (date) 2 Yes, ANC ≥ 500/mm3 for 3 lab values with subsequent decline in ANC to < 500/mm3 for ≥ 3 days (dates) 3 No, ANC ≥ 500/mm3 was not achieved and there was no evidence of recurrent disease in the bone marrow 4 No, ANC ≥500/mm3 was not achieved and there was documented persistent disease in the bone marrow postHSCT 5 ANC never dropped below 500/mm3 at any time after the start of the preparative regimen 3 Form 2100 Is (was) there evidence of hematopoietic recovery following the initial HSCT? (check only one) 1 Yes, ANC ≥ 500/mm3 achieved and sustained for 3 lab values with no subsequent decline (date) 2 Yes, ANC ≥ 500/mm3 for 3 lab values with subsequent decline in ANC to < 500/mm3 for ≥ 3 days (dates) 3 No, ANC ≥ 500/mm3 was not achieved and there was no evidence of recurrent disease in the bone marrow 4 No, ANC ≥500/mm3 was not achieved and there was documented persistent disease in the bone marrow postHSCT 5 ANC never dropped below 500/mm3 at any time after the start of the preparative regimen Duration of Neutropenia Affected by both rate and depth of decline and rate of recovery Reduced intensity regimens may lead to slow or small decreases in cell counts – no or short period of neutropenia What Does “Never” Below Mean? Not in the early posttransplant period when engraftment usually occurs (first 28 days) Not until you do something to make them go below (e.g., additional chemotherapy) Neutrophil Recovery Varies by Graft Type and Conditioning Regimens 3000 2500 MA-BM MA-PB MA-cord RIC NST 2000 1500 1000 500 0 1 4 7 10 13 16 19 22 25 28 31 34 37 40 Neutrophil Recovery ≠ Engraftment Myeloablative Regimens Engraftment implies presence of donor cells Must be proved by chimerism studies 4 Very low intensity regimens: gradual transition from host to donor without cytopenia What Affects Recovery Rate? Donor type: Auto > HLA-id > HLA ≠ Graft type: PB > BM > CB Cell dose: High > Low Conditioning regimen: More intense > less intense GVHD prophylaxis: MTX ↓ Infection: may suppress counts What About Graft Failure and Autologous Recovery Graft Failure – persistent ANC <500/mm3 Does not include the “wiggling” sometimes seen in early posttransplant period Includes failure to ever get to 500 and decline d li to t <500 after ft initial i iti l recovery Does not necessarily mean graft rejection (which implies that the recipient cells have immunologically rejected the donor cells) Autologous recovery – requires proving the cells are host cells What Affects Graft Failure Risk? Disease: Malignant < Non-malignant Donor type: Auto <<< HLA-id < HLA ≠ Cell dose: High < Low Conditioning regimen: More intense < less intense Infection: particularly viral infection Some drugs WHAT IS A BOOST? Additional cells given to facilitate hematopoietic recovery No additional conditioning Generally uses cells previously stored Autologous – does not require second transplant form Allogeneic – does require a second transplant form Reasons are operational not biologic 5
